Decisions involved in a molecular ecology workflow   [ 12 ]  Samples can be collected from a variety of different environments using appropriate collection techniques. DNA is then prepared and used to answer a variety of ecological questions: metabarcoding is used to answer questions about "who" is present, while the function of communities or individuals can be established using a  metagenomics , single‐cell genomics or  metatranscriptomics . [ 12 ]


Visualization and diversity metrics from environmental sequencing data   [ 12 ]  a)  Alpha diversity  displayed as taxonomy bar charts, showing relative abundance of taxa across samples using the Phinch data visualization framework (Bik & Pitch Interactive 2014).   b)  Beta diversity  patterns illustrated via Principal Coordinate Analyses carried out in  QIIME , [ 48 ]  where each dot represents a sample and colors distinguish different classes of sample. The closer two sample points in 3D space, the more similar their community assemblages  c) GraPhalAn phylogenetic visualization of environmental data, with circular  heatmaps  and abundance bars used to convey quantitative taxon traits. [ 49 ]  d) Edge PCA, a tree‐based diversity metric that identifies specific lineages (green/orange branches) that contribute most to community changes observed in samples distributed across different PCA axes. [ 50 ] [ 51 ]


Arthropod predators and vertebrate predators in a millet field  [ 77 ]   (A) Trophic network: of arthropod and vertebrate predators – arrows represent biomass flow between predators and preys.   (B) Intraguild interactions:  * Arthropod predators * Parasitoids of arthropods: * Insectivorous vertebrates: [ 77 ]


Metabarcoding eDNA and eRNA in marine biosecurity  Global biodiversity of  operational taxonomic units  (OTUs) for DNA-only, shared eDNA/eRNA, and RNA-only datasets. Charts show the relative abundance of sequences at highest assigned taxonomic levels. [ 99 ]


A region of the  gene  for the  cytochrome c oxidase   enzyme  is used to distinguish species in the  Barcode of Life Data Systems  database.


Hyder, Avery, MacLeod and McCarty used strands of purified  DNA  such as this, precipitated from solutions of cell components, to perform  bacterial transformations


Avery and his colleagues showed that DNA was the key component of  Griffith's experiment , in which mice are injected with dead bacteria of one strain and live bacteria of another, and develop an infection of the dead strain's type.


Oswald Avery


Colin MacLeod


Maclyn McCarty  (with  Watson  and  Crick )


Overview of experiment and observations


Scientist Martha Chase and Alfred Hershey


Structural overview of T2 phage


The two possibilities tested by the Luria–Delbrück experiment. (A) If mutations are induced by the media, roughly the same number of mutants are expected to appear on each plate. (B) If mutations arise spontaneously during cell divisions prior to plating, each plate will have a highly variable number of mutants.


Example of a T-REx system controlling the expression of  shRNA


Vigorous growth of seedlings during TROPI on Expedition 22. In this phase of the experiment, plants were oriented since they grew in 1-g from an on-board centrifuge.


This nucleotide contains the five-carbon sugar  deoxyribose  (at center), a  nucleobase  called  adenine  (upper right), and one  phosphate  group (left). The deoxyribose sugar joined only to the nitrogenous base forms a  Deoxyribonucleoside   called  deoxyadenosine , whereas the whole structure along with the phosphate group is a  nucleotide , a constituent of DNA with the name  deoxyadenosine monophosphate .


Showing the arrangement of nucleotides within the structure of nucleic acids: At lower left, a monophosphate nucleotide; its nitrogenous base represents one side of a base-pair. At the upper right, four nucleotides form two base-pairs: thymine and adenine (connected by  double  hydrogen bonds) and guanine and cytosine (connected by  triple  hydrogen bonds). The individual nucleotide monomers are chain-joined at their sugar and phosphate molecules, forming two 'backbones' (a  double helix ) of nucleic acid, shown at upper left.


Structural elements of three nucleo tides —where one-, two- or three-phosphates are attached to the nucleo side  (in yellow, blue, green) at center: 1st, the nucleotide termed as a  nucleoside  mono phosphate  is formed by adding a phosphate (in red); 2nd, adding a second phosphate forms a  nucleoside  di phosphate ; 3rd, adding a third phosphate results in a  nucleoside  tri phosphate . + The nitrogenous base ( nucleobase ) is indicated by  "Base"  and " glycosidic bond " (sugar bond). All five  primary, or canonical, bases —the  purines  and  pyrimidines —are sketched at right (in blue).


The synthesis of  UMP .     enzymes      coenzymes      substrate names      metal ions      inorganic molecules


The  biosynthetic  origins of purine ring  atoms N 1  arises from the amine group of  Asp C 2  and C 8  originate from  formate N 3  and N 9  are contributed by the amide group of  Gln C 4 , C 5  and N 7  are derived from  Gly   C 6  comes from HCO 3 −  (CO 2 )


Diagram of the synthesis of IMP.     enzymes      coenzymes      substrate names      metal ions      inorganic molecules


The cycle of synthesis and degradation of ATP; 1 and 2 represent output and input of energy, respectively.


Glycolysis overview


ATP-Synthase


Interactive animation of the structure of ATP


The cycles of synthesis and degradation of ATP; 2 and 1 represent input and output of energy, respectively.


This image shows a 360-degree rotation of a single, gas-phase  magnesium -ATP chelate with a charge of −2. The anion was optimized at the UB3LYP/6-311++G(d,p) theoretical level and the atomic connectivity modified by the human optimizer to reflect the probable electronic structure.


An example of the Rossmann fold, a  structural domain  of a  decarboxylase  enzyme from the bacterium  Staphylococcus epidermidis  ( PDB :  1G5Q ) with a bound  flavin mononucleotide  cofactor


Aminoallyl uridine (aa-UTP)


Hierarchically clustered heat map using aa-dUTPs [ 1 ]


Process of preparing amino-allyl labeled cDNA


Chemical structures of other BNAs that were synthesized in the past years as indicated below the structures.


Chemical structures of BNAs were introduced in 2007 by Imanishi's group. [ 7 ]  These new generation of BNAs analogues are called 2',4'-BNA NC [NH], 2',4'-BNA NC [NMe], and 2',4'-BNA NC [NBn].


Makoto Koizumi in 2004 reviewed the properties of BNAs with focus on ENAs as antisense and antigen oligonucleotides (AONs) and proposed an action mechanism for these compounds that may involve translation arrest, mRNA degradation mediated by RNase H and splicing arrest.


Synthesis of Cangrelor


The CDP-choline pathway; enzymes named in green.


Enzymes involved in reactions are identified by numbers. See file description.


cAMP represented in three ways


Adenosine triphosphate


Cyclic di-AMP crystal structure


c-di-AMP synthesis and degradation reaction


Ball and Stick model of the cyclic guanosine monophosphate molecule, Color code: Carbon, C: black Hydrogen, H: white Oxygen, O: red Nitrogen, N: blue   Phosphorus, P: orange.


Schematic of cGMP and a broad overview of its effects


role of PKG in cellular system


Cyclic adenosine monophosphate .  The cyclic portion refers to the two single bonds between the  phosphate  group and the  ribose


Cyclic guanosine monophosphate .  The cyclic portion refers to the two single bonds between the  phosphate  group and the  ribose


Generic cyclic nucleotide biosynthesis reaction by cyclase


Generic hydrolysis reaction of 3' cNMP phosphodiester bond by phosphodiesterase


Molecular structure of 2',3'-dideoxyadenosine triphosphate (ddATP)


Inhibition of a nucleophilic attack due to the absence of the 3'-OH Group


Reaction of FAD to form FADH 2


Approximate absorption spectrum for FAD


Mechanism 1. Hydride transfer occurs by addition of H +  and 2 e −


Mechanism 2. Hydride transfer by abstraction of hydride from NADH


Mechanism 3. Radical formation by electron abstraction


Mechanism 4. The loss of hydride to electron deficient R group


Mechanism 5. Use of nucleophilic addition to break R 1 -R 2  bond


Mechanism 6. Carbon radical reacts with O 2  and acid to form H 2 O 2


Indication of the origin and terminus of DNA replication on a GC skew and cumulative GC skew plot.


Richness of G over T in the leading strand, resulting in a GC skew sign at the origin and terminus.


Cumulative CG and AT skew for 49 bacterial chromosomes


Phosphoribosylamine (PRA)


This figure shows the pathway described: IMP synthesis.


Glutamine-PRPP-amidotransferase


Poliovirus  genome, including an IRES.


The  redox  reactions of nicotinamide adenine dinucleotide


UV  absorption spectra of NAD +  and NADH [ image reference needed ]


Some  metabolic pathways  that synthesize and consume NAD +  in  vertebrates . [ image reference needed ]  The abbreviations are defined in the text.


Salvage pathways use three precursors for NAD + .


Rossmann fold  in part of the  lactate dehydrogenase  of  Cryptosporidium parvum , showing NAD +  in red, beta sheets in yellow, and alpha helices in purple [ 47 ]


In this diagram, the hydride acceptor C4 carbon is shown at the top. When the nicotinamide ring lies in the plane of the page with the carboxy-amide to the right, as shown, the hydride donor lies either "above" or "below" the plane of the page. If "above" hydride transfer is class A, if "below" hydride transfer is class B. [ 56 ]


A simplified outline of redox  metabolism , showing how NAD +  and NADH link the  citric acid cycle  and  oxidative phosphorylation [ image reference needed ]


The structure of  cyclic ADP-ribose


Arthur Harden , co-discoverer of NAD


Cell stimuli select different Ca 2+  stores by synthesising different second messengers. Shown for comparison are the ER-targeting messengers, IP 3  and cADPR.


Speculative pathways for NAADP synthesis and degradation. ADP-ribosyl cyclase (ARC) family members (such as CD38) can synthesise NAADP via the base-exchange reaction (NicAcid, Nicotinic Acid; NiAm, nicotinamide). NAADP may be broken down to NAAD via a Ca 2+ -sensitive phosphatase, or to 2-phosphoadenosine diphosphoribose (ADPRP) by CD38 itself. For simplicity, enzyme topology has been ignored (see below). [ citation needed ]


Simplified pathways regulating luminal Ca 2+  (left) and pH (right) in acidic organelles. Ca 2+  uptake can be mediated either by a Ca 2+ /H +  exchanger (CHX, that exploits the pH gradient) or a Ca 2+  pump (powered by ATP hydrolysis). The low luminal pH is driven by the H +  pump, the  V-ATPase , and aided by essential counterion movements, e.g. chloride uptake, that acts as a charge shunt essential for optimal proton uptake. [ citation needed ]


Numbered  ribose  carbons on  cytidine .


The Stave Projection uses spatially distributed dots to enhance the legibility of  DNA  sequences.


AmbiScript uses ambigrams to reflect DNA symmetries and support the manipulation and analysis of genetic data.


Schematic showing the structure of nucleoside triphosphates. Nucleosides consist of a 5-carbon sugar (pentose) connected to a nitrogenous base through a 1' glycosidic bond. Nucleotides are nucleosides with a variable number of phosphate groups connected to the 5' carbon. Nucleoside triphosphates are a specific type of nucleotide. This figure also shows the five common nitrogenous bases found in DNA and RNA on the right.


In nucleic acid synthesis, the 3’ OH of a growing chain of nucleotides attacks the α-phosphate on the next NTP to be incorporated (blue), resulting in a phosphodiester linkage and the release of pyrophosphate (PP i ). This figure shows DNA synthesis, but RNA synthesis occurs through the same mechanism.


The energy released during hydrolysis of adenosine tripshophate (ATP), shown here, is frequently coupled with energetically unfavourable cellular reactions.


Binding of a ligand to a G protein-coupled receptor allows GTP to bind the G protein. This causes the alpha subunit to leave and act as a downstream effector.


The salvage of pyrimidine ribonucleotides.


Activation of Monosaccharides


Structure of adenosine 5′-phosphosulfate (APS).


General chemical structure of a phosphorimidazolide reagent


Isopentenyl pyrophosphate  (IPP) and  dimethylallyl pyrophosphate  (DMAPP) condense to produce  geranyl pyrophosphate , precursor to all terpenes and terpenoids.


Activation of remdesivir into its active triphosphate metabolite [ 33 ]


Synthesis of remdesivir in  structural formulae


Phytic acid


TNP BINDING


Comparison of conventional plant breeding with  transgenic  and  cisgenic  genetic modification


In 1974  Rudolf Jaenisch  created a  genetically modified mouse , the first GM animal.


Polymerase chain reaction  is a powerful tool used in  molecular cloning .


A gene gun uses  biolistics  to insert DNA into plant tissue.


A. tumefaciens  attaching itself to a carrot cell


Knockout mice


Human cells in which some proteins are fused with  green fluorescent protein  to allow them to be visualised


Bt-toxins present in  peanut  leaves (bottom image) protect it from extensive damage caused by  lesser cornstalk borer   larvae  (top image). [ 126 ]


An illustration of  viral vector -mediated  gene transfer  using an  adenovirus  as the vector


The Editosome Complex


The effect of uracil insertion in pre-mRNA transcripts


The effect of C-to-U RNA editing on the human ApoB gene


Summary of the Various Functions of RNA Editing


An illustration of 2A peptide function: when the  CDS  of a 2A peptide is inserted between two coding sequences, the peptide will be translated into two unbound proteins, due to ribosome skipping (i.e. not due to cleavage as shown in the figure).


Structure of AcrIIA4 obtained with the UCSF Chimera software, [ 12 ]  where its PDB file was uploaded. [ 13 ]  Different colours were assigned to the four different secondary structures found in this protein: blue for β-strands, red for α-helices, orange for the 3 10  helix, and grey for loops. Originally, the PDB file contains the 20 lowest energy sequences (and thus, the most stable ones) superposed, one of which was randomly selected to create the figure. [ 14 ]


Phage-phage cooperation:  First phage infections may be unable to hamper the CRISPR immunity, but phage-phage cooperations increasingly boost Acr production and host immunosuppression, which produces an increase on the vulnerability of the host cell to reinfection, and finally allows a successful infection and spreading of a second phage.   Based on a representation found in the 17th reference.   [ 17 ]


Diagram showing type I-F CRISPR-Cas system, as well as inhibition mechanisms of three type I-F anti-CRISPRs. Type I-F CRISPR complex is made of 60 crRNA nucleotides and nine Cas proteins (the protein type is specified by the numbers 5,8,7,6). AcrF1 goes to Cas7f, preventing target DNA access to the crRNA guide. AcrF2 interacts both with Cas8f and Cas7f, difficulting target DNA access to the binding pocket. Finally, AcrF3 forms a  homodimer , interacting with Cas3 by preventing its contact with the Cascade complex.  Based on a representation from a review found in the references below.   [ 21 ]


Phage therapy  could be used against antibiotic resistance, as bacteriophages can kill bacteria, and cure an infection.


Phage therapy is a good alternative to the use of antibiotics, but some bacteria have CRISPR-Cas systems. Nevertheless, if phages had Acr proteins, they would inhibit the CRISPR-Cas immune system and infect the cell. At the end of the phage reproduction cycle, which takes place inside bacteria, new phages would be released, provoking the cell lysis.


Angora goat at the Texas State Fair.


Anatomy of a bioreporter organism.  Upon exposure to a specific analyte, the promoter/reporter gene complex is transcribed into messenger RNA (mRNA) and then translated into a reporter protein that is ultimately responsible for generating a signal.


Bioluminescence emitted from colonies of microbial cells containing the genes for bacterial luciferase.


Positive-pressure biosafety suit


International Biohazard Warning Symbol


Color overlay showing constituent parts of Blasticidin S


The  Max Planck Institute for Infection Biology  in Berlin, Germany


Emmanuelle Charpentier in the Senate Chamber of York University in 2016, after giving her Gairdner Foundation International Award Lecture


Schematic of chemically induced dimerization.  Two proteins that do not normally interact (top) bind in the presence of a dimerizing agent (bottom).


Potatoes after treatment with  Phytophthora infestans . The normal potatoes have blight but the cisgenic potatoes are healthy


A diagram comparing the genetic changes achieved through conventional plant breeding, transgenesis and cisgenesis


Diagram showing how to generate a conditional knockout mouse: A mouse containing the Cre gene and a mouse containing the lox gene were bred to generate a conditional knockout for a particular gene of interest. The mice do not naturally express Cre recombinase or lox sites, but they have been engineered to express these gene products to create the desirable offspring.


Scheme of DNA cloning in a cosmid vector.


Diagram of the CRISPR prokaryotic antiviral defense mechanism [ 8 ]


Simplified diagram of a CRISPR locus. The three major components of a CRISPR locus are shown:  cas  genes, a leader sequence, and a repeat-spacer array. Repeats are shown as gray boxes and spacers are colored bars. The arrangement of the three components is not always as shown. [ 29 ] [ 30 ]  In addition, several CRISPRs with similar sequences can be present in a single genome, only one of which is associated with  cas  genes. [ 31 ]


A diagram of the CRISPR nucleases  Cas12a  and  Cas9  with the position of DNA cleavage shown relative to their  PAM sequences  in a zoom-in


The stages of CRISPR immunity for each of the three major types of adaptive immunity.  (1) Acquisition begins by recognition of invading DNA by  Cas1  and Cas2 and cleavage of a protospacer.  (2) The protospacer is ligated to the direct repeat adjacent to the leader sequence and  (3) single strand extension repairs the CRISPR and duplicates the direct repeat. The crRNA processing and interference stages occur differently in each of the three major CRISPR systems.  (4) The primary CRISPR transcript is cleaved by cas genes to produce crRNAs.  (5) In type I systems Cas6e/Cas6f cleave at the junction of ssRNA and dsRNA formed by hairpin loops in the direct repeat. Type II systems use a trans-activating (tracr) RNA to form dsRNA, which is cleaved by  Cas9  and RNaseIII. Type III systems use a Cas6 homolog that does not require hairpin loops in the direct repeat for cleavage.  (6) In type II and type III systems secondary trimming is performed at either the 5' or 3' end to produce mature crRNAs.  (7) Mature crRNAs associate with Cas proteins to form interference complexes.  (8) In type I and type II systems, interactions between the protein and PAM sequence are required for degradation of invading DNA. Type III systems do not require a PAM for successful degradation and in type III-A systems basepairing occurs between the crRNA and mRNA rather than the DNA, targeted by type III-B systems.


The CRISPR genetic locus provides bacteria with a defense mechanism to protect them from repeated phage infections.


Transcripts of the CRISPR Genetic Locus and Maturation of pre-crRNA


3D structure of the CRISPR-Cas9 interference complex


CRISPR-Cas9 as a molecular tool introduces targeted double strand DNA breaks.


Double-strand DNA breaks introduced by CRISPR-Cas9 allows further genetic manipulation by exploiting endogenous DNA repair mechanisms.


Complementary base pairing between the sgRNA and genomic DNA allows targeting of Cas9 or dCas9


The dCas9-VPR activator increases transcription at the gene that it targets.


The dCas-SAM system uses msgRNA that has attached aptamers for different transcriptional factors (MS2,p65 and HSF1) to bind.


The use of the Suntag system allows multiple antibodies fused to VP64 to bind to dCas9-Suntag. That in turn recruits RNA polymerase and increases gene expression.


Cas12a and Cas9 nucleases and their DNA cleavage positions


DNA repair after double-stranded break


Overview of CRISPR-Cas9 plasmid construction


Overview of the transfection and DNA cleaving by CRISPR-Cas9 (crRNA and tracrRNA are often joined as a single strand of RNA when designing a plasmid) [ 58 ]


Different CRISPR DNA nucleases with their PAM and size


Simplified flowchart for CRISPR based diagnostics like SHERLOCK [ 218 ]


Schematic flowchart of molecular detection methods for COVID-19 virus [ 219 ]


A dead Cas9 protein coupled with epigenetic modifiers which are used to repress certain genome sequences rather than cutting it all together [ 10 ]


A visual overview of how TALE proteins are used for epigenome editing


Transcription activator assay  used to verify sgRNA/Cas9 complex targeting activity, and the proper integrity of the added RNA module. Direct activation: The transcription activator, VP64, is fused to the Cas9 protein, so proper targeting of the complex results in reporter gene activation. Bridged activation: VP64 is fused to PP7, which recognizes and binds a sequence in the RNA module when the RNA module is properly folded.


CRISPR-Display allows addition of RNA modules to the sgRNA for a range of functionalities, such as ectopic lncRNA localization, recruitment of endogenous or engineered RNA binding proteins for gene regulation, or affinity tagging for live cell imaging. The functions can be performed simultaneous in the same cell.


Process of pre-implantation genetic diagnosis.  In vitro  fertilisation involves either incubation of sperm and oocyte together, or injection of sperm directly into the oocyte. PCR - polymerase chain reaction, FISH - fluorescent  in situ  hybridisation.


CRISPR-Cas9. PAM (Protospacer Adjacent Motif) is required for target binding.


DNA repair after double-strand break


He Jiankui speaking at the Second International Summit on Human Genome Editing, November 2018


Figure 1: A ddRNAi construct encoding a shRNA is packaged into a delivery  vector  (or reagent) tailored to target specific cells. Inside the cell, the  DNA  is transported to the  nucleus  where  transcription  machinery continually manufactures the encoded RNAs. The shRNA molecules are then processed by endogenous systems before entering the  RNAi  pathway and silencing the desired genes. [ 1 ]


Figure 2: ddRNAi DNA constructs


Cornfield ( Zea mays  subsp.  mays ))


Wheat ear


The Four Core Genotypes mouse model produces four types of offspring. Mice with ovaries (green) can have XX or XY sex chromosomes. Mice with testes (orange) can have XX or XY sex chromosomes. A difference in phenotype in mice with different sex chromosomes (XX vs. XY) shows a sex chromosome effect. A difference in phenotype in mice with different type of gonad shows the effects of gonadal hormones.


Bacterial transformation involves moving a gene from one bacteria to another. It is integrated into the recipients plasmid. and can then be expressed by the new host.


A gene gun uses  biolistics  to insert DNA into plant tissue.


A. tumefaciens  attaching itself to a carrot cell


In 1974,  Rudolf Jaenisch  created the first GM animal.


Some  chimeras , like the blotched mouse shown, are created through genetic modification techniques like  gene targeting .


Transgenic pig for cheese production


Herman the Bull on display in  Naturalis Biodiversity Center


Animal welfare and ethics resources


Plants ( Solanum chacoense ) being transformed using agrobacterium


Transgenic maize  containing a gene from the bacteria  Bacillus thuringiensis


Genetically modified  King Edward potato  (right) next to King Edward which has not been genetically modified (left). Research field belonging to the  Swedish University of Agricultural Sciences  in 2019.


GM crops production in the World (ISAAA Brief 2019)     More than 10 million hectares      Between 50,000 and 10 million hectares      Less than 50,000 hectares      No biotech crops


Land area used for genetically modified crops by country (1996–2009), in millions of hectares. In 2011, the land area used was 160 million hectares, or 1.6 million square kilometers. [ 54 ]


Three views of a papaya, cultivar "Sunset", which was genetically modified to create the cultivar 'SunUp', which is resistant to  Papaya ringspot virus [ 106 ]


Plums  genetically engineered for resistance to  plum pox , a disease carried by  aphids


Golden rice is genetically modified for an increased nutrient level, which has a different color and vitamin A content.


Green: Mandatory labeling required; Red: Ban on import and cultivation of genetically engineered food.


Application of genetically modified food throughout the globe.


The genetically modified mouse in which a gene affecting hair growth has been knocked out (left) shown next to a normal lab mouse


Transgenic mice expressing  green fluorescent protein , which glows green under blue light. The central mouse is  wild-type .


Suntory "blue" rose


Kenyans examining insect-resistant transgenic  Bt  corn


A  double helix  of natural DNA.  Hachimoji DNA adopts a similar structure.


An artist's impression of a  humanzee , or chimpanzee-human hybrid


President   George W. Bush , pictured here in 2008 with then  Interior Secretary   Dirk Kempthorne  to his side, has advocated for increased  regulation of genetic engineering , including on research mixing animal and human elements.


The pig-like hybrid being  Zhu Bajie , pictured in this piece of  fan art , plays a major role in the famous  Ming dynasty  era religious novel  Journey to the West .


This image depicts a set of  Tanuki  statues on the side of a Japanese road.


Ganesha , who has an  elephant 's head, is one of the most revered entities in the  Hindu pantheon .


Human mitochondrial genome showing hypervariable regions I to III (green boxes) located in the control region (CR; grey box).


18th Transgenic Technology Meeting 2023 in Houston, USA


Wild-type  Physcomitrella  and knockout mosses: Deviating  phenotypes  induced in gene-disruption library transformants.  Physcomitrella  wild-type and transformed plants were grown on minimal Knop medium to induce differentiation and development of  gametophores . For each plant, an overview (upper row; scale bar corresponds to 1 mm) and a close-up (bottom row; scale bar equals 0.5 mm) are shown. A: Haploid wild-type moss plant completely covered with leafy gametophores and close-up of wild-type leaf. B–E: Different mutants. [ 1 ]


The technique utilizes native  ADAR  enzymes (pictured with RNA).


LEAPER-mediated RNA Editing [ 2 ]


Site saturation mutagenesis  is a type of  site-directed mutagenesis . This image shows the saturation mutagenesis of a single position in a theoretical 10-residue protein. The wild type version of the protein is shown at the top, with M representing the first amino acid methionine, and * representing the termination of translation. All 19 mutants of the isoleucine at position 5 are shown below.


How DNA libraries generated by  random mutagenesis  sample sequence space. The amino acid substituted into a given position is shown. Each dot or set of connected dots is one member of the library. Error-prone PCR randomly mutates some residues to other amino acids. Alanine scanning replaces each residue of the protein with alanine, one-by-one. Site saturation substitutes each of the 20 possible amino acids (or some subset of them) at a single position, one-by-one.


Depiction of one common way to clone a site-directed mutagenesis library (i.e., using degenerate oligos). The gene of interest is PCRed with oligos that contain a region that is perfectly complementary to the template (blue), and one that differs from the template by one or more nucleotides (red). Many such primers containing degeneracy in the non-complementary region are pooled into the same PCR, resulting in many different PCR products with different mutations in that region (individual mutants shown with different colors below).


Workflow for screening a synthetic library to identify cells producing a chemical of interest.


Ganesha, with Elephant's head


Horus, with Falcon's head


A  medieval  depiction of a harpy as a bird-woman


'Gajasimha', Museum of Cham Sculpture


A nure-onna as depicted in Sawaki Suushi's  Hyakkai-Zukan


A Centaur fighting a man


Pegasus, as the horse of Muses, was put on the roof of  Poznań Opera House  ( Max Littmann , 1910)


Detail of the embroidered dress of an Apkallu, showing a pair of 4-legged winged animals. From Nimrud, Iraq. 883-859 BCE. Ancient Orient Museum, Istanbul


Satyr men, satyr women, and satyr children.


Garuda carrying his master Vishnu. Garuda has an eagle's head, wings and legs


Assyrian   lamassu  dated 721, BCE Oriental Institute Museum, University of Chicago.


Horns of a  goat  and a  ram , goat's fur and ears, nose and canines of a  pig , and mouth of a  dog , a typical depiction of the devil in  Christian art . The goat, ram, dog and pig are animals consistently associated with the Devil. [ 17 ]  Detail of a 16th-century painting by  Jacob de Backer  in the  National Museum  in  Warsaw .


Navagunjara, has limb representing eight animals, including a human hand.


Cecaelia is a half human, half octopus.


This image shows how OE-PCR might be utilized to splice two DNA sequences (red and blue). The arrows represent the 3' ends


This image shows how OE-PCR might be utilized to delete a sequence from a DNA strand


The image depicts the 3 main steps of OE-PCR Reaction.


Components of prime editing


Prime editing mechanism


PE3 system for prime editing


This diagram provides a visual representation of provirus integration in the same or convergent orientation to the host gene. Generated using SnapGene® software (from Dotmatics; available at snapgene.com).


Schematic depicting the targeted integration of the payload between the essential gene and endogenous promoter for stable expression. [ 10 ]


The law indicates that a  QR code  could suffice as a GMO label


World map of GMO agriculture (hectares) [ 1 ]


Diagram illustrating the development process of  avian flu  vaccine by reverse genetics techniques


Wild-type  Physcomitrella patens  and  knockout mosses : Deviating  phenotypes  induced in gene-disruption library transformants.  Physcomitrella  wild-type and transformed plants were grown on minimal Knop medium to induce differentiation and development of  gametophores . For each plant, an overview (upper row; scale bar corresponds to 1 mm) and a close-up (bottom row; scale bar equals 0.5 mm) are shown. A: Haploid wild-type moss plant completely covered with leafy gametophores and close-up of wild-type leaf. B–E: Different mutants. [ 3 ]


A schematic representation of one timestamp with repetitive RNA motifs and MS2 binding sites. Adenosines gradually convert to inosines and are ultimately read as guanosines after RNA-sequencing.


A workflow schematic of RNA timestamps represented in 4 steps (adapted from image by Rodriques et al.)  [ 1 ]   1- depicts tagging the RNA of interest. 2-shows the RNA timestamp: three MS2 binding domains with repetitive adenosine editing regions that ADARcd2 (shown as ADAR) binds in order to convert A-to-I overtime. 3 & 4 - analysis steps.


Tyr- and Ser-SSRs from prokaryotes  (phages; grey)  and eukaryotes  (yeasts; brown); a comprehensive overview (including references) can be found in. [ 6 ]


Recombination patterns depending on recombinase (sub-)family and target-site orientation.   GOI, "gene of interest"; [+/-], a positive-negative selection marker such as the hygtk-fusion gene. Note that interaction of two identical substrate sites (loxP x loxP or FRT x FRT) leads to products of the same composition, whereas recombination of two non-identical educts leads to two different hybrid sites (attP x attB → attR + attL)


A unified "tag-&-exchange strategy.  Tag-and-exchange strategy relying on homologous recombination (HR; tagging step) followed by RMCE (SSR; exchange step). The figure illustrates analogous double-reciprocal crossover principles for HR and RMCE, the major difference being the dramatically different requirements for homologous sequences, which are in the kb-range for HR but as short as ~50 bp for SSRs


Fused protoplast (left) with chloroplasts (from a leaf cell) and coloured vacuole (from a petal)


Polymerase Cycling Assembly. Blue arrows represent oligonucleotides 40 to 60 bp with overlapping regions of about 20 bp. The cycle is repeated until the final genome is constructed.


Gibson Assembly Method. The blue arrows represent DNA cassettes, which could be any size, 6 kb each for example. The orange segments represent areas of identical DNA sequences. This process can be carried out with multiple initial cassettes.


Gap Repair Cloning. The blue arrows represent DNA contigs. Segments of the same colour represent complementary or identical sequences. Specialized primers with extensions are used in a polymerase chain reaction to generate regions of homology at the terminal ends of the DNA contigs.


Transformation-Associated Recombination. Cross over events occur between regions of homology across the cassettes and YAC vector, thereby connecting the smaller DNA sequences into one larger contig.


Gibson assembly method. The blue arrows represent DNA cassettes, which could be any size, 6 kb each for example. The orange segments represent areas of identical DNA sequences. This process can be carried out with multiple initial cassettes.


Toehold mediated strand displacement


Spacefill drawing of dimeric TALE-FokI fusion (blue: TALE; green: FokI) bound to DNA ( PDB :  1FOK ,  3UGM ), by David Goodsell


Workflow of genome editing of Your Favorite Gene (YFG) using TALEN. The target sequence is identified, a corresponding TALEN sequence is engineered and inserted into a plasmid. The plasmid is inserted into the target cell where it is translated to produce the functional TALEN, which enters the nucleus and binds and cleaves the target sequence. Depending on the application, this can be used to introduce an error (to knock out a target gene) or to introduce a new DNA sequence into the target gene.


Julian Huxley , the biologist who popularised the term  transhumanism  in an influential 1957 essay [ 6 ]


Ray Kurzweil  believes that a countdown to when " human life will be irreversibly transformed " can be made through plotting major world events on a graph.


In the U.S., the  Amish  are a religious group most known for their avoidance of certain modern technologies. Transhumanists draw a parallel by arguing that in the near-future there will probably be "humanish", people who choose to "stay human" by not adopting human enhancement technologies. They believe their choice must be respected and protected. [ 146 ]


Plastid examples


Plant gene cassette schematic for plant transplastomics


Example of a tomato plant grafting for agricultural purposes


Nicotiana tobacco plant


Potato beetle larvae


Artist impression of an aurochs bull found in  Braunschweig ,  Germany .


Aurochs in a cave painting in Lascaux, France


The former distribution range of the Aurochs


Site of a vaccinia injection, several days later.


1950s US smallpox vaccine, produced by the National Drug Company in Philadelphia from  vaccinia [ 31 ]


Gene therapy using an  adenovirus  vector.


CCTV for low vision


Base pairing: Two  base pairs  are produced by four nucleotide monomers, nucleobases are  in blue . Guanine (G) is paired with cytosine (C) via  three   hydrogen bonds ,  in red . Adenine (A) is paired with uracil (U) via  two  hydrogen bonds,  in red .


Purine nucleobases are fused-ring molecules.


Pyrimidine nucleobases are simple ring molecules.


Chemical structure of DNA, showing four nucleobase pairs produced by eight nucleotides: adenine (A) is joined to thymine (T), and guanine (G) is joined to cytosine (C). + This structure also shows the  directionality  of each of the two phosphate-deoxyribose backbones, or strands. The 5' to 3' ( read  "5 prime to 3 prime") directions are:  down  the strand on the left, and  up  the strand on the right. The strands twist around each other to form a double helix structure.


Adenine structure, with standard numbering of positions in red.


Adenine on Crick and Watson's DNA molecular model, 1953. The picture is shown upside down compared to most modern drawings of adenine, such as those used in this article.


Hydrogen bonding (dashed lines) between unnatural bases in hachimoji DNA


The biosynthesis of base J.  A : thymidine hydroxylase;  B : beta-glucosyltranferase;  1 : dT (desoxy thymidine);  2 : HOCH3dU;  3 : dJ


The chemical structure of DNA base-pairs


Schematic  karyogram  of a human. The blue scale to the left of each nuclear chromosome pair (as well as the  mitochondrial genome  at bottom left) shows its length in terms of mega–base-pairs. Further information:  Karyotype


Mutagenesis by 5BU


DiampurineT DNA base pair


Isoguanine-Isocytosine-base-pair


Synthesis of isocytosine from malic acid


Tautomerism of isocytosine


Deamination of 5-methylcytosine to thymine


Addition of methyl group to cytosine


Methylthiouracil synthesis: [ 1 ]


Thyroid hormone synthesis , with the oxidation step labeled at center-left.


Ball-and-stick model of uracil


Space-filling model of uracil


Uracil  tautomers :  Amide  or  lactam  structure (left) and  imide  or  lactim  structure (right)


Chemical structure of uridine


Epigenetic mechanisms


Number of patent families and non-patent documents with the term "epigenetic*" by publication year


DNA associates with histone proteins to form chromatin.


Some acetylations and some methylations of lysines (symbol K) are activation signals for transcription when present on a  nucleosome , as shown in the top figure.   Some methylations on lysines or arginine (R) are repression signals for transcription when present on a  nucleosome , as shown in the bottom figure.   Nucleosomes  consist of four pairs of  histone  proteins in a tightly assembled core region plus up to 30% of each histone remaining in a loosely organized tail [ 34 ]  (only one tail of each pair is shown). DNA is wrapped around the histone core proteins in  chromatin . The lysines (K) are designated with a number showing their position as, for instance (K4), indicating lysine as the 4th amino acid from the amino (N) end of the tail in the histone protein.  Methylations  [Me], and  acetylations  [Ac] are common  post-translational modifications  on the lysines of the histone tails.


Initiation of  DNA demethylation  at a  CpG site . In adult somatic cells DNA methylation typically occurs in the context of CpG dinucleotides ( CpG sites ), forming  5-methylcytosine -pG, or 5mCpG. Reactive oxygen species (ROS) may attack guanine at the dinucleotide site, forming  8-hydroxy-2'-deoxyguanosine  (8-OHdG), and resulting in a 5mCp-8-OHdG dinucleotide site. The  base excision repair  enzyme  OGG1  targets 8-OHdG and binds to the lesion without immediate excision. OGG1, present at a 5mCp-8-OHdG site recruits  TET1  and TET1 oxidizes the 5mC adjacent to the 8-OHdG. This initiates demethylation of 5mC. [ 100 ]


including medial prefrontal cortex (mPFC)


Cytosine and 5-methylcytosine


Escherichia coli  bacteria


Summary of the role of  TET enzymes  and  5-hydroxymethylcytosine  (5hmC) in mammalian neurobiology.


a. Each row represents a CpG probe (binding to each  CpG site  where  DNA demethylation  can occur), and each column represents an individual's sample. The color scale from blue to red indicates the  DNA methylation  level, ranging from 0 (no methylation) to 1 (fully methylated). The episignatures of  pathogenic  TET3 mutations display DNA hypermethylation in comparison to  matched  and family  controls . b.  Multidimensional scaling  was performed to stratify TET3  variants of uncertain significance  (VUS) as either pathogenic or benign, based on their episignatures. Note:  bi-allelic  (BA); mono-allelic (MA)


Figure 1: Outline of bisulfite conversion of sample sequence of genomic DNA. Nucleotides in blue are unmethylated cytosines converted to uracils by bisulfite, while red nucleotides are 5-methylcytosines resistant to conversion.


Figure 2: Outline of the chemical reaction that underlies the bisulfite-catalyzed conversion of cytosine to uracil.


Figure 3: DNA methylation analysis methods not based on methylation-specific PCR. Following bisulfite conversion, the genomic DNA is amplified with PCR that does not discriminate between methylated and non-methylated sequences. The numerous methods available are then used to make the discrimination based on the changes within the amplicon as a result of bisulfite conversion.


Figure 4: Methylation-specific PCR is a sensitive method to discriminately amplify and detect a methylated region of interest using methylated-specific primers on bisulfite-converted genomic DNA.  Such primers will anneal only to sequences that are methylated, and thus containing  5-methylcytosines  that are resistant to conversion by bisulfite.  In alternative fashion, unmethylated-specific primers can be used.


Epigenetics patterns in a normal and cancer cells


Epigenetic alterations in tumour progression


A  DNA  molecule fragment that is methylated at two cytosines


A chart of common DNA damaging agents, examples of lesions they cause in DNA, and pathways used to repair these lesions. Also shown are many of the genes in these pathways, an indication of which genes are epigenetically regulated to have reduced (or increased) expression in various cancers. It also shows genes in the error prone microhomology-mediated end joining pathway with increased expression in various cancers.


decitabine


Steps in nucleosome assembly. CAF-1 is shown in yellow interacting with the H3-H4 tetramer.


Chromatin organization: The basic unit of chromatin organization is the nucleosome, which comprises 147 bp of DNA wrapped around a core of histone proteins. The level of nucleosomal packaging can have profound consequences on all DNA-mediated processes including gene regulation. Euchromatin (loose or open chromatin) structure is permissible for transcription whereas heterochromatin (tight or closed chromatin) is more compact and refractory to factors that need to gain access to the DNA template. Nucleosome positioning and chromatin compaction can be influenced by a wide range of processes including modification to both histones and DNA and ATP-dependent chromatin remodeling complexes. [ 2 ]


INO80 stabilizes replication forks and counteracts mislocalization of H2A.Z


Chromatin remodeling complexes in the dynamic regulation of transcription: In the presence of acetylated histones (HAT mediated) and absence of methylase (HMT) activity, chromatin is loosely packaged. Additional nucleosome repositioning by chromatin remodeler complex,  SWI/SNF  opens up DNA region where transcription machinery proteins, like RNA Pol II, transcription factors and co-activators bind to turn on gene transcription. In the absence of SWI/SNF, nucleosomes can not move farther and remain tightly aligned to one another. Additional methylation by HMT and deacetylation by HDAC proteins condenses DNA around histones and thus, make DNA unavailable for binding by RNA Pol II and other activators, leading to gene silencing.


Figure 01: Functional domains of the CHD subfamily of ATP-dependent chromatin remodelers


DNA methylation is an epigenetic mechanism that can be studied with bioinformatics.


ChIP-on-chip technique


Pyrophosphate leaving group in a condensation reaction forming the ribose-phosphate polymer. Condensation of Adenine and Guanine forming a phosphodiester bond, the basis of the nucleic acid backbone.


Basic units of genomic organization in bacteria and eukaryotes.


Different levels of DNA condensation in eukaryotes. (1) Single DNA strand. (2)  Chromatin  strand (DNA with histones). (3) Chromatin during  interphase  with  centromere . (4) Two copies of condensed chromatin together during  prophase . (5) Chromosome during  metaphase .


DNA methylation is the addition of a  methyl  group to the DNA that happens at  cytosine . The image shows a cytosine single ring base and a methyl group added on to the 5 carbon. In mammals, DNA methylation occurs almost exclusively at a cytosine that is followed by a  guanine .


Methylation levels during mouse early embryonic development.


Brain regions involved in memory formation


Demethylation of 5-methylcytosine. Demethylation of 5-methylcytosine (5mC) in neuron DNA. As reviewed in 2018, [ 19 ]  in brain neurons, 5mC is oxidized by a TET dioxygenase to generate  5-hydroxymethylcytosine  (5hmC). In successive steps a  TET enzyme  further hydroxylates 5hmC to generate 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Thymine-DNA glycosylase (TDG) recognizes the intermediate bases 5fC and 5caC and cleaves the glycosidic bond resulting in an apyrimidinic site (AP site). In an alternative oxidative deamination pathway, 5hmC can be oxidatively deaminated by activity-induced cytidine deaminase/apolipoprotein B mRNA editing complex (AID/APOBEC) to form 5-hydroxymethyluracil (5hmU). 5mC can also be converted to thymine (Thy). 5hmU can be cleaved by TDG, single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1), Nei-Like DNA glycosylase 1 (NEIL1), or methyl-CpG binding protein 4 (MBD4). AP sites and T:G mismatches are then repaired by base excision repair (BER) enzymes to yield cytosine (Cyt).


Initiation of DNA demethylation at a  CpG site . In adult somatic cells DNA methylation typically occurs in the context of CpG dinucleotides ( CpG sites ), forming  5-methylcytosine -pG, (5mCpG). Reactive oxygen species (ROS) may attack guanine at the dinucleotide site, forming  8-hydroxy-2'-deoxyguanosine  (8-OHdG), and resulting in a 5mCp-8-OHdG dinucleotide site. The  base excision repair  enzyme  OGG1  targets 8-OHdG and binds to the lesion without immediate excision. OGG1, present at a 5mCp-8-OHdG site recruits  TET1  and TET1 oxidizes the 5mC adjacent to the 8-OHdG. This initiates demethylation of 5mC [ 25 ]  as shown in the previous figure.


An example of base excision repair of 5-formylcytosine (5fC) (adjacent to 8-OHdG, an oxidized guanine) by short patch repair or long patch repair. Two strands of DNA are represented by parallel horizontal lines. The first downward arrow shows thymine DNA glycosylase (TDG) removing 5-formylcytosine (5fC) from the DNA backbone, leaving an apyrimidinic site. Then AP endonuclease cleaves the 5′ deoxyribose-phosphate in the DNA backbone of a single strand, leaving a 3′ hydroxy end and a 5′ deoxyribose phosphate end (second downward arrow). This is followed by either short patch or long patch repair. In short patch repair, 5′ dRP lyase trims the 5′ dRP end to form a phosphorylated 5′ end. This is followed by  DNA polymerase β  (Pol β) adding a single cytosine opposite the pre-existing guanine in the complementary strand and then DNA ligase to seal the cut strand. In long patch repair, DNA synthesis is thought to be mediated by  polymerase δ  and  polymerase ε  performing displacing synthesis to form a flap. Pol β can also perform long-patch displacing synthesis. Long-patch synthesis typically inserts 2–10 new nucleotides. Then  flap endonuclease  removes the flap, and this is followed by  DNA ligase  to seal the strand.


Representation of a  DNA  molecule that is methylated. The two white spheres represent  methyl groups . They are bound to two  cytosine   nucleotide  molecules that make up the DNA sequence.


Typical DNA methylation landscape in mammals


Cytosine methylation then deamination to Thymine


Dynamic of DNA methylation during mouse embryonic development. E3.5-E6, etc., refer to days after fertilization. PGC: primordial germ cells.


Possible pathways of cytosine methylation and demethylation. Abbreviations:  S-Adenosyl-L-homocysteine  ( SAH ),  S-adenosyl-L-methionine  ( SAM ),  DNA methyltransferase  ( DNA MTase ),  Uracil-DNA glycosylase  ( UNG )


All methylations in a prokaryote . In some prokaryotic organisms, all three previously known DNA methylation types are represented (N4-methylcytosine: m4C, 5-methylcytosine: m5C and N6-methyladenine: m6A). Six examples are shown here, two of which belong to the Archaea domain and four of which belong to the Bacteria domain. The information comes from Blow et al. (2016). [ 96 ]  In the left column are the species names of the organisms, to the right there are examples of methylated DNA motifs. The full names of the archaea and bacterial strains are according to the NCBI taxonomy: "Methanocaldococcus jannaschii DSM 2661", "Methanocorpusculum labreanum Z", "Clostridium perfringens ATCC 13127", "Geopsychrobacter electrodiphilus DSM 16401", "Rhodopseudomonas palustris CGA009" and "Salmonella enterica subsp. enterica serovar Paratyphi A str. ATCC 9150"


Cold weather affects the likelihood of a butterfly finding a mate and reproducing, as well as their coloring. These insects are dependent on their coloring to survive and reproduce.


DNA Replication


Epigenetic mechanisms-DNA methylation and acetylation


Regulation of transcription in mammals


Top: Normal dynamic of  histone acetylation  leads to open and closed chromatin genome-wide and changes in gene expression. Middle: HDAC inhibition repressed the closed-open change favoring an open chromatin state and gene expression. Bottom: Epigenetic priming general model. Starting with an hypothetical closed chromatin state a priming stimuli sensitizes the chromatin to other stimuli and subsequently increase transcription.


Cancer cell sensitization to treatment through epigenetic priming. Normal cells with activated tumor suppressor genes (TSG) and Cancer cell with inactivated TSG through epigenetic mechanisms (showing only acetylation for simplification purposes). Priming stimuli performed with DNMT and/or HDAC inhibitors following by immunotherapy treatment (second stimuli) leading to reactivation of TSG.


Epigenetic mechanisms


Mechanism of miRNAs


A diagram of epigenetic therapy


Honeybees (Apis mellifera) marked after hatching with colour


Figure 1  HDAC inhibition enhances memory and synaptic plasticity through CREB:CBP. Figure adapted from Vecsey  et al.  (2007) [ 24 ]


Regulatory sequence in a promoter at a transcription start site with a paused RNA polymerase and a TOP2B-induced double-strand break


Brain regions involved in memory formation including medial prefrontal cortex (mPFC)


Initiation of  DNA demethylation  at a  CpG site . In adult somatic cells DNA methylation typically occurs in the context of CpG dinucleotides ( CpG sites ), forming  5-methylcytosine -pG, or 5mCpG. Reactive oxygen species (ROS) may attack guanine at the dinucleotide site, forming  8-hydroxy-2'-deoxyguanosine  (8-OHdG), and resulting in a 5mCp-8-OHdG dinucleotide site.  The  base excision repair  enzyme  OGG1  targets 8-OHdG and binds to the lesion without immediate excision. OGG1, present at a 5mCp-8-OHdG site recruits  TET1  and TET1 oxidizes the 5mC adjacent to the 8-OHdG.  This initiates demethylation of 5mC. [ 34 ]


Demethylation of  5-Methylcytosine  (5mC) in neuron DNA.  As reviewed in 2018, [ 9 ]  in brain neurons, 5mC is oxidized by the ten-eleven translocation (TET) family of dioxygenases ( TET1 ,  TET2 ,  TET3 ) to generate  5-hydroxymethylcytosine  (5hmC).  In successive steps TET enzymes further hydroxylate 5hmC to generate 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC).   Thymine-DNA glycosylase  (TDG) recognizes the intermediate bases 5fC and 5caC and excises the  glycosidic bond  resulting in an apyrimidinic site ( AP site ).  In an alternative oxidative deamination pathway, 5hmC can be oxidatively deaminated by activity-induced cytidine deaminase/apolipoprotein B mRNA editing complex  (AID/APOBEC)  deaminases to form 5-hydroxymethyluracil (5hmU) or 5mC can be converted to  thymine  (Thy).  5hmU can be cleaved by TDG, single-strand-selective monofunctional uracil-DNA glycosylase 1 ( SMUG1 ), Nei-Like DNA Glycosylase 1 ( NEIL1 ), or methyl-CpG binding protein 4 ( MBD4 ).  AP sites and T:G mismatches are then repaired by base excision repair (BER) enzymes to yield  cytosine  (Cyt).


During DNA methylation, cytosine is methylated.


During histone acetylation, lysines are acetylated.


Irene Shashar, a Holocaust survivor of the Warsaw Ghetto, addressing MEPs


Mental health disorders that can be caused by epigenetic alterations


Epigenetic DNA Methylation


A discoid lupus erythematosus lesion


Psoriasis  plaque on an elbow


Person with  Alopecia areata  on the scalp


HPA axis diagram


Human herpes virus


Herpes simplex virions


Epstein–Barr virus


Cytomegalovirus


Kaposi sarcoma


Para-sagittal MRI of the head in a patient with benign familial macrocephaly


The nucleus of a human cell showing the location of euchromatin


Chromosome 21


Alpha motor neurons are derived from the  basal plate  (basal lamina).


Brain-derived neurotrophic factor


This is a transverse section of the striatum from a structural  MR image . The striatum, in red, includes the  caudate nucleus  ( top ), the  putamen  ( right ), and, when including the term 'corpus' striatum, the  globus pallidus  ( lower left ).


Lewy bodies


Some acetylations and some methylations of lysines (symbol K) are activation signals for transcription when present on a  nucleosome , as shown in the top figure.  Some methylations on lysines or arginine (R) are repression signals for transcription when present on a  nucleosome , as shown in the bottom figure.   Nucleosomes  consist of four pairs of  histone  proteins in a tightly assembled core region plus up to 30% of each histone remaining in a loosely organized tail [ 4 ]  (only one tail of each pair is shown).  DNA is wrapped around the histone core proteins in  chromatin .  The lysines (K) are designated with a number showing their position as, for instance (K4), indicating lysine as the 4th amino acid from the amino (N) end of the tail in the histone protein.  Methylations  [Me], and  acetylations  [Ac] are common  post-translational modifications  on the lysines of the histone tails.


Regulation of transcription in mammals.  An active enhancer  regulatory sequence  of DNA is enabled to interact with the  promoter  DNA regulatory sequence of its target  gene  by formation of a chromosome loop.


Skeletal muscle  cell types include: very large multinuclear  muscle fiber cells ; small  endothelial cells  that line the inside of capillary blood vessels; small fibro-adipogenic progenitor cells (FAPs) which are muscle-fiber-adjacent multipotent mesenchymal stem cells that under different conditions can differentiate into  adipocytes ,  fibroblasts  or  osteocytes .  Also shown are  pericytes  situated on the outer surface of blood  capillaries  where they interact with the underlying  endothelial cells .  In addition,  satellite cells  are shown that can fuse with  muscle fibers  and contribute new  myonuclei  to muscle fibers, grow into  new myocytes , or support focal membrane damage repair. [ 10 ]


A  nucleosome  with  histone  tails set for transcriptional activation


A visualization of the stress-vulnerability model, also known as the diathesis-stress model


The limbic system and associated structures of the brain, where abnormalities lead to positive symptoms of schizophrenia


Mechanisms of epigenetics in the cell


The function of DNA strands (yellow) alters depending on how it is organized around  histones  (blue) that can be methylated (green).


EWAS workflow


Methylation assay workflow. From:  Illumina Methylation Assay


Work flow for EWA study


This figure depicts the general workflow for epiphenotyping, focusing on the use of machine learning to generate valid models for predicting phenotypes from DNA methylation patterns.


The figure shows examples of applications of epiphenotyping and some different phenotypes that models can predict from DNA methylation data.


General mechanism utilized by ribozymes to cleave RNA molecules


Left: Overview of RNA interference.


Structure of a typical Gram-positive bacterial cell


Crystallographic structure of the N-terminal region of the human huntingtin protein.


Basic mechanism used by viral vectors to deliver genes to target cells. Example shown is a lentiviral vector.


Bernard Crespi, the primary originator of the hypothesis, in 2016


Recognition sites of available MD DNA Endonucleases


DNMT3 and GLAI equal specificity


GLAD-PCR assay


Lysine acetylation


Immunohistochemical comparison of DMG with EHZIP overexpression (top) to DMG with H3K27M mutation (bottom). Loss of M3K27me3 (left) is visible in both samples, while H3K27M (middle) and EZHIP (right) only stain in one of the samples, respectively.


Arginine methylation by type I and II PRMTs.


Schematic representation of the assembly of the core histones into the nucleosome


Histone heterooctamer (H3,H4,H2A,H2B) + DNA fragment, Frog


Steps in nucleosome assembly


Basic units of chromatin structure


Histone tails and their function in chromatin formation


Schematic representation of histone modifications. Based on Rodriguez-Paredes and Esteller, Nature, 2011


Relative sizes and locations of important domains for representative HATs (HAT = catalytic acetyltransferase domain; Bromo = bromodomain; Chromo = chromodomain; Zn = zinc finger domain). The number of amino acid residues in each HAT is indicated at the right in each example.


Crystal structure of Tetrahymena Gcn5 with bound coenzyme A and histone H3 peptide (PDB 1QSN). The central core (green), flanking N- and C-terminal segments (blue), coenzyme A (orange), and histone peptide (red) are shown.


Catalytic mechanisms of GNAT and MYST family HATs. (A) General mechanism of GNAT HATs. (B) General mechanism of MYST HATs.


Schematic showing the role of HATs in gene transcription.


Front view of the human enzyme Histone Lysine N-Methyltransferase, H3 lysine-4 specific.


Epigenetic mechanisms


Back view of the human enzyme Histone Lysine N-Methyltransferase, H3 lysine-4 specific.  Active sites clearly visible.


Active site of Histone Lysine N-Methyltransferase.  Lysine residue (in yellow) and S-Adenosyl methionine (SAM) (in blue) clearly visible.


DNA  is wrapped around  histones  to form  nucleosomes . Nucleosomes are shown as " beads on a string " with the distinction between  euchromatin  and  heterochromatin .


The basic units of  chromatin  structure.


The dynamic state of histone acetylation/deacetylation regulated by  HAT  and  HDAC  enzymes; acetylation of histones alters accessibility of chromatin.


A  phosphoryl group  is shown in blue.


An  O-GlcNAcylated   threonine  residue. The  GlcNAc  moiety is shown in red while the modified threonine is shown in black.


An  adenosine diphosphate ribose  group.


The amino acid  arginine  (left) is converted to  citrulline  (right) via the process of  citrullination .


Proline  trans-cis isomerization  by a  PPIase  enzyme.


Cycle for methanogenesis, showing intermediates


The methylation reaction catalyzed by  methionine synthase


The  Eschweiler–Clarke reaction  is used to methylate amines.


Diagram of the  hypothalamic–pituitary–adrenal axis


Basic units of  chromatin  structure


The crystal structure of the nucleosome core particle consisting of   H2A  ,   H2B  ,   H3   and   H4   core histones, and DNA. The view is from the top through the superhelical axis.


Apoptotic DNA laddering . Digested chromatin is in the first lane; the second contains DNA standard to compare lengths.


Scheme of nucleosome organization [ 27 ]


The crystal structure of the nucleosome core particle ( PDB :  1EQZ  [ 28 ] )


The current chromatin compaction model


Histone tails and their function in chromatin formation


Diagram of nucleosome assembly


Steps in nucleosome assembly


Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1


Transgenerational effects of maternal protein restriction


The nutriepigenetic pathway of maternal choline-deficient diets helps to elucidate the development of fetal alcohol syndrome.


Paramutation was first observed by the effect it had on the color of corn kernels in maize plants


Arginine methylation by type I and II PRMTs


Lysine methylation by PKMTs and demethylation by PKDMs


Timeline of DNA methylation in the mouse  genome . Red: female  germ line ; blue: male germ line; grey:  somatic cell  line; PGCs:  primordial germ cells ; ICM:  inner cell mass .


DNA methylation dynamic during mouse embryonic development


Brain regions involved in memory formation


Demethylation of 5-methylcytosine.  Demethylation of 5-methylcytosine (5mC) in neuron DNA. As reviewed in 2018, [ 11 ]  in brain neurons, 5mC is oxidized by a TET dioxygenase to generate  5-hydroxymethylcytosine  (5hmC).  In successive steps a TET enzyme further hydroxylates 5hmC to generate  5-formylcytosine  (5fC) and 5-carboxylcytosine (5caC). Thymine-DNA glycosylase (TDG) recognizes the intermediate bases 5fC and 5caC and cleaves the glycosidic bond resulting in an apyrimidinic site (AP site). In an alternative oxidative deamination pathway, 5hmC can be oxidatively deaminated by activity-induced cytidine deaminase/apolipoprotein B mRNA editing complex (AID/APOBEC) to form 5-hydroxymethyluracil (5hmU).  5mC can also be converted to thymine (Thy). 5hmU can be cleaved by TDG, single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1), Nei-Like DNA glycosylase 1 (NEIL1), or methyl-CpG binding protein 4 (MBD4). AP sites and T:G mismatches are then repaired by base excision repair (BER) enzymes to yield cytosine (Cyt).


Initiation of DNA demethylation at a  CpG site .  In adult somatic cells DNA methylation typically occurs in the context of CpG dinucleotides ( CpG sites ), forming  5-methylcytosine -pG, (5mCpG). Reactive oxygen species (ROS) may attack guanine at the dinucleotide site, forming  8-hydroxy-2'-deoxyguanosine  (8-OHdG), and resulting in a 5mCp-8-OHdG dinucleotide site.  The  base excision repair  enzyme  OGG1  targets 8-OHdG and binds to the lesion without immediate excision. OGG1, present at a 5mCp-8-OHdG site recruits  TET1  and TET1 oxidizes the 5mC adjacent to the 8-OHdG.  This initiates demethylation of 5mC [ 17 ]  as shown in the previous figure.


Somatic Cell Nuclear Transfer . The nucleus of a somatic cell is transferred into an oocyte that has had its original nucleus removed. [ 36 ]  That oocyte will take in the genetic material from the somatic cell and divide into a totipotent cell. [ 35 ]  Created with BioRender.com


Cell Fusion . Two cells can be fused together and share nuclear DNA, creating a  heterokaryon , which can then have the nuclease fuse, creating a hybrid. [ 35 ]  Created with BioRender.com


Defined factors. The addition of  microRNA ,  transcription factor , epigenetic markers, and other small molecules or a combination of these can induce cellular reprogramming by causing the expression of other genes. [ 30 ] [ 35 ]  Created with BioRender.com


Stem cells  are defined as undifferentiated cells that can differentiate into three  germ layers . The ability of self-renewal, through  telomerase  extending the  telomere  of  chromosomes , allows the stem cell population to be maintained at a constant. As the  induced pluripotent stem cells  are passaged, the epigenetic memory of the cells diminishes and the cells gradually want to differentiate into any cell type rather than the original somatic cell type. [ 33 ]


Some chromosomal sex determination systems in animals


Drosophila sex-chromosomes


Human male XY chromosomes after  G-banding


Heredity of sex chromosomes in XO sex determination


Haplodiploid sex chromosomes


All alligators determine the sex of their offspring by the temperature of the nest.


Life cycle of clownfish


The ends of the XY chromosomes in a human cell in  metaphase , highlighted here in green, are all that is left of the original autosomes that can still  cross over  with each other.


In humans, the SRY gene is located on short (p) arm of the  Y chromosome  at position 11.2


The human Y chromosome showing the SRY gene which codes for a protein regulating sexual differentiation.


Figure One: The mesonephric System Pathway  [ 7 ]


Development of external genitalia


SIR spreading is thought to occur linearly from the silencer element.


SIR2 homodimer (green) in complex with SIR4's (purple) SIR2-interacting domain (SID;yellow) [ 20 ]


The  centriole , an  organelle  involved in  cell division , is structurally inherited.


DNA methylation is the addition of a  methyl  group to the DNA that happens at  cytosine . The image shows a cytosine single ring base and a methyl group added on to the 5 carbon. In mammals, DNA methylation occurs almost exclusively at a cytosine that is followed by a  guanine .


Demethylation of 5-methylcytosine.  Demethylation of 5-methylcytosine (5mC) in neuron DNA.


Initiation of  DNA demethylation  at a  CpG site


The conversion of 5-methylcytosine to 5-hydroxymethylcytosine by TET enzyme plus a-ketoglutarate & Fe(II)


Methylation levels during mouse early embryonic development.


Brain regions involved in memory formation


. Brain structures connected to addiction


"Intergenerational" vs "transgenerational" inheritance


Blending inheritance  leads to the averaging out of every characteristic, which as the engineer  Fleeming Jenkin  pointed out, makes evolution by natural selection impossible.


The coloration of  tortoiseshell  and  calico cats  is a visible manifestation of X-inactivation. The black and orange  alleles  of a fur coloration gene reside on the X chromosome. For any given patch of fur, the inactivation of an X chromosome that carries one allele results in the fur color of the other, active allele.


The process and possible outcomes of random X- chromosome  inactivation in female human embryonic cells undergoing  mitosis .   1.Early stage embryonic cell of a female human   2.Maternal X chromosome   3.Paternal X chromosome   4.Mitosis and random X-chromosome inactivation event   5.Paternal chromosome is randomly inactivated in one daughter cell, maternal chromosome is inactivated in the other   6.Paternal chromosome is randomly inactivated in both daughter cells   7.Maternal chromosome is randomly inactivated in both daughter cells   8.Three possible random combination outcomes


Nucleus of a female cell. Top: Both X-chromosomes are detected, by  FISH . Bottom: The same nucleus stained with a DNA stain ( DAPI ). The Barr body is indicated by the arrow, it identifies the inactive X (Xi).


An interphase female human fibroblast cell. [ 1 ]  Arrows point to sex chromatin on DNA ( DAPI ) in cell nucleus(left), and to the corresponding X chromatin (right). Left: DNA (DAPI)-stained nucleus. Arrow indicates the location of Barr body(Xi). Right: DNA associated  histones  protein detected


The figure shows  confocal microscopy  images from a combined RNA-DNA  FISH  experiment for  Xist  in fibroblast cells from adult female mouse, demonstrating that Xist RNA is coating only one of the X-chromosomes. RNA FISH signals from Xist RNA are shown in red color, marking the inactive X-chromosome (Xi). DNA FISH signals from Xist loci are shown in yellow color, marking both active and inactive X-chromosomes (Xa, Xi). The nucleus ( DAPI -stained) is shown in blue color. The figure is adapted from:. [ 2 ]


Some of the different types of gene-environment interplay. Adapted from Jaffee and Price, Psychiatry, 2008  [ 5 ]  and Flowers, Froelicher & Aouizerat, European Journal of Cardiovascular Nursing, 2012  [ 4 ]


Schematic representation of epigenetic histone modifications. Based on Rodriguez-Paredes and Esteller, Nature, 2011


A section of  DNA ; the sequence of the plate-like units ( nucleotides ) in the center carries information.


A  Punnett square  showing how two brown haired parents can have red or brown haired children. 'B' is for brown and 'b' is for red.


Red hair is a  recessive  trait.


Genes are expressed by being  transcribed  into RNA, and this RNA then  translated  into protein.


DNA replication . DNA is unwound and  nucleotides  are matched to make two new strands.


Mice  with different coat colors


A  cat  hair showing light and dark bands caused by alternating production of  agouti-signaling protein  and  α-MSH .


Both of these mice are viable yellow agouti a vy ; however, the mouse on the right does not express it due to epigenetic methylation.


An agouti dog, also called wolf sable


The pale areas on this bay horse are due to the pangaré trait


The allotype affects the constant region (labeled CL and CH1-3 in the diagram.)


FDA microbiologist prepares DNA samples for gel electrophoresis analysis


Electrophoresis apparatus


Karyotype of chromosomes


Strength of natural selection plot as a function of age


Early  embryos  of various species display some ancestral features, like the tail on this human embryo. These features normally disappear in later development, but it may not happen if the animal has an atavism. [ 1 ] [ 2 ]


The expected  genotypic frequencies  of novel mutations from autogamous crosses and geitonogamous crosses.


This image demonstrates backcrossing of a heterozygous mouse from one genetic background onto another genetic background. In this example, the gene knockout is performed on 129/Sv cells and then backcrossed into the C57B/6J genetic background. With each successive backcross, the percentage of C57B/6J DNA that constitutes the genome of the offspring is increased.


Nucleus of a female amniotic fluid cell. Top: Both X-chromosome territories are detected by  FISH . Shown is a single optical section made with a  confocal microscope . Bottom: Same nucleus stained with  DAPI  and recorded with a  CCD camera . The Barr body is indicated by the arrow, it identifies the inactive X (Xi).


Left:  DAPI  stained female human fibroblast with Barr body (arrow). Right:  histone  macroH2A1 staining. Arrow points to sex chromatin in DAPI-stained cell nucleus, and to the corresponding sex chromatin site in the histone macroH2A1-staining.


Enzymes, biosynthetic intermediates and subcellular location of the pathway are indicated. [ citation needed ]


Blood type (or blood group) is determined, in part, by the ABO blood group antigens present on red blood cells.


ABO blood group system : diagram showing the carbohydrate chains that determine the ABO blood group


Simplified  Punnett square  of the possible genotypes and phenotypes of children given genotypes and phenotypes of their mother (rows) and father (columns) shaded by phenotype


Main symptoms of  acute hemolytic reaction  due to blood type mismatch. [ 25 ] [ 26 ]


Red blood cell compatibility chart In addition to donating to the same blood group; type O blood donors can give to A, B and AB; blood donors of types A and B can give to AB.


Plasma compatibility chart In addition to donating to the same blood group; plasma from type AB can be given to A, B and O; plasma from types A, B and AB can be given to O.


A hospital worker takes samples of blood from a donor for testing


The BLOSUM62 matrix, the amino acids have been grouped and coloured based on  Margaret Dayhoff's  classification scheme. Positive and zero values have been highlighted.


Schematic of bump-and-hole method. [ 1 ]


The first reported bump-and-hole pair. Hole-modified S99T/F113A mutant cyclophilin has an expanded hydrophobic pocket to accept a methyl bump in cyclosporin A analog MeIle11CsA. [ 4 ]


The bumped ATP analog N6-cyclopentyl ATP cannot bind wild type v-Src kinase, but can bind its bump-and-hole pair, I338G v-Src kinase. [ 8 ]


The bumped ET inhibitor has selectivity for L94A BET BD due to steric complementarity. The un-bumped I-BET inhibitor would promiscuously bind BDs. [ 13 ]


Schematic of bumped pro-drug and hole-modified enzyme, releasing the drug only in the presence of the bump-and-hole pair. [ 18 ]


Hole-modified BH GalNac-Ts paired with UDP-GalNac analogs to tag GalNac T substrates to be visualized with click chemistry. [ 19 ]


Effects of EFF-1 and AFF-1 on vesicle morphology.


Crossing over during meiosis, with chiasma shown.


DNA segment with three genes, showing a double recombination event. If the individual recombination rates (between A and B; and between B and C) are known, then the c.o.c. between the regions AB and BC can be calculated from the rate of double recombination.


This stylistic schematic diagram shows a gene in relation to the double helix structure of  DNA  and to a  chromosome  (right).  Introns  are regions often found in  eukaryote  genes which are removed in the  splicing  process: only the  exons  encode the  protein . This diagram labels a region of only 40 or so bases as a gene. In reality most genes are hundreds of times larger and have several Introns, sometimes over 100.


Schematic  karyogram  of a typical human cell during the  G 0  phase  in relation to the  cell cycle , which is most common phase among human cells, and wherein there will be two pairs of each chromosome (designated 2n), each with one copy of each  locus  (for a total of 2c). In contrast, at center top it also shows the chromosome 3 pair in  metaphase , which is among the phases occurring after  DNA synthesis  but before  cell division , where each chromosome will have two copies of each locus, connected at the  centromere , for a total of 2n and 4c. Further information:  Karyotype


Green frog  Lithobates clamitans  unexpectedly grows faster in montane populations


Cell in  anaphase  the chromosomes having split and the  kinetochore  microtubules shrinking


A nursery in a project aiming at the  de novo  domestication of  Thinopyrum intermedium  (intermediate wheatgrass), a perennial grain.


Lyudmila Trut  with a  domesticated silver fox , 1974


Guide to fingerprint identification


Symmetry of female and male faces. Those with high symmetry appear more attractive than low.


Diagram of both distylous morphs


Example of distyly in Primula. A. L-morph (pin), B. S-morph (thrum)  1. petal. 2 sepal. 3 anther. 4 pistil.


DNase I  hypersensitive  sites within  chromatin [ 1 ]


Reduction in size is regarded as a domestication syndrome trait -  grey wolf  skull compared with a  chihuahua  skull


In ten publications on domestication syndrome in animals, no single trait is included in every one. [ 13 ]


Proteins required for ectodermal specification.


Endocycling vs. endomitosis


Notch regulation of endocycling


Structural model of the enhanceosome. Double-stranded  DNA  is shown in green and pink; the ATF-2/ c-Jun   coiled-coil  DNA binding domain is shown in purple;  interferon response factors  are shown in beige; and  NF kappa B  is shown in orange (p105 subunit) and blue (p65 subunit).


Expression of all 8  Hox genes  in the fruit fly  Drosophila melanogaster


Distinction between  genome , exome, and  transcriptome .  The exome consists of all of the exons within the genome. In contrast, the trascriptome varies between cell types (e.g. neurons vs cardiac cells), only involving a portion of the exons that are actually transcribed into mRNA.


Mitochondria contain their own  DNA . They are passed on by mothers to their children via the cytoplasm of the egg.


English:  Phase and Antigenic Variation in Bacteria. pA is the promoter for FimA, pB is the promoter for FimB and pE is the promoter for FimE. IRR is inverted repeat right and IRL is inverted repeat left. FimB and FimE are recombinases that can change the orientation of the FimA promoter by inverting the IRR and IRL.


The figure shows the chemical compounds ethyl methansulfonate (shown on the left) and N-ethyl-N-nitrosourea (shown on the right).


Flowchart of basic steps involved in forward genetics approach.


An example GAL4-UAS system, with GAL4 lines and UAS reporter lines.


Thomas Hunt Morgan 's  Drosophila melanogaster   genetic linkage   map . This was the first successful  gene map  produced and provides important evidence for the  Boveri–Sutton chromosome theory  of  inheritance . The map shows the relative positions of  allelic  characteristics on the second Drosophila chromosome. The distance between the genes (map units) are equal to the percentage of  crossing-over  events that occurs between different alleles. [ 1 ]


First genetic map (Sturtevant, 1913). It shows 6 sex-linked genes.


Genetic map of drosophila, published in  The theory of the gene  1926 edition. [ 14 ]


Example of a genetic regulatory circuit for  Drosophila melanogaster's   huckebein   (hkb)  gene's effects on gap gene expression.


Animation of DNA, a part of our identity.


Comparison of typical phage (bacteriophage) infection and transduction ( A ) with typical GTA (gene transfer agent) production and transduction ( B ).


Methods for detecting gene transfer agents.  ( A ) Method used by Marrs in 1974.  ( B ) Cell-free extract method.


Typical prophage and GTA gene clusters.


Schematic diagram of phylogenetic relationships between known bacterial gene transfer agents.


The evolutionary forces that act on bacterial gene transfer agent and the cells that produce it.


Typical steps in the production of bacterial gene transfer agents. ( 1 ) Transcription and translation of the GTA genes. ( 2 ) Assembly of GTA structural proteins into empty heads and unattached tails. ( 3 ) Packaging of 'headful' segments of DNA into heads and attachment of tails. ( 4 ) Lysis of the cell.


Genetic transduction by bacterial gene transfer agents. ( 1 ) GTA particles encounter a suitable recipient cell.  ( 2 ) Particles attach to cell and inject their DNA, and cellular proteins translocate the DNA across the inner membrane. ( 3 ) DNA is degraded if it cannot recombine with the recipient genome. ( 4 ) DNA with similar sequences to the recipient genome undergoes recombination.


Regulation diagram for RcGTA, the Rhodobacter capsulatus gene transfer agent


A  least weasel .


An  olive baboon   grooming  the hair of another.


A very simple genotype–phenotype map that only shows additive pleiotropy effects.


A speculative framework for the evolutionary history underlying current-day phenotypic variation in human skin pigmentation based on the similarities and differences found in various genotypes. [ 6 ]


A series of codons in part of a  messenger RNA  (mRNA) molecule. Each codon consists of three  nucleotides , usually corresponding to a single  amino acid . The nucleotides are abbreviated with the letters A, U, G and C. This is mRNA, which uses U ( uracil ). DNA uses T ( thymine ) instead. This mRNA molecule will instruct a  ribosome  to synthesize a protein according to this code.


The genetic code


Reading frames in the DNA sequence of a region of the human mitochondrial genome coding for the genes  MT-ATP8  and  MT-ATP6  (in black: positions 8,525 to 8,580 in the sequence accession NC_012920 [ 31 ] ). There are three possible reading frames in the 5' → 3' forward direction, starting on the first (+1), second (+2) and third position (+3). For each codon (square brackets), the amino acid is given by the  vertebrate mitochondrial code , either in the +1 frame for  MT-ATP8  (in red) or in the +3 frame for  MT-ATP6  (in blue). The  MT-ATP8  genes terminates with the TAG stop codon (red dot) in the +1 frame. The  MT-ATP6  gene starts with the ATG codon (blue circle for the M amino acid) in the +3 frame.


Examples of notable  mutations  that can occur in humans [ 35 ]


Grouping of codons by amino acid residue molar volume and  hydropathicity .  A  more detailed version  is available.


Axes 1, 2, 3 are the first, second, and third positions in the codon. The 20 amino acids and stop codons (X) are shown in  single letter code .


Genetic code  logo  of the  Globobulimina pseudospinescens  mitochondrial genome by FACIL. The program is able to correctly infer that the  Protozoan Mitochondrial Code  is in use. [ 57 ]  The logo shows the 64 codons from left to right, predicted alternatives in red (relative to the standard genetic code). Red line: stop codons. The height of each amino acid in the stack shows how often it is aligned to the codon in homologous protein domains. The stack height indicates the support for the prediction.


Population bottleneck can decrease genetic viability leading to possible extinction  [ 3 ]


Portrait of  Imre Festetics  the first  geneticist  and  ethologist . His concepts of  selection  and  evolution  were later formulated in  Charles Darwin's theory of evolution .


Blending inheritance  leads to the averaging out of every characteristic, which as the engineer  Fleeming Jenkin  pointed out, makes  evolution  by  natural selection  impossible.


Morgan's observation of  sex-linked inheritance  of a mutation causing white eyes in  Drosophila  led him to the hypothesis that genes are located upon chromosomes.


DNA , the molecular basis for  biological inheritance . Each strand of DNA is a chain of  nucleotides , matching each other in the center to form what look like rungs on a twisted ladder.


A  Punnett square  depicting a cross between two pea plants heterozygous for purple (B) and white (b) blossoms


Genetic pedigree charts help track the inheritance patterns of traits.


Human height is a trait with complex genetic causes.  Francis Galton 's data from 1889 shows the relationship between offspring height as a function of mean parent height.


The  molecular structure  of DNA. Bases pair through the arrangement of  hydrogen bonding  between the strands.


Schematic  karyogram  of a human, showing 22  homologous chromosome  pairs, both the female (XX) and male (XY) versions of the  sex chromosome  (bottom right), as well as the  mitochondrial genome  (at bottom left)  Further information:  Karyotype


Walther Flemming 's 1882 diagram of eukaryotic cell division. Chromosomes are copied, condensed, and organized. Then, as the cell divides, chromosome copies separate into the daughter cells.


Thomas Hunt Morgan 's 1916 illustration of a double crossover between chromosomes


The  genetic code : Using a  triplet code , DNA, through a  messenger RNA  intermediary, specifies a protein.


Siamese cats  have a temperature-sensitive pigment-production mutation.


Transcription factors bind to DNA, influencing the transcription of associated genes.


Gene duplication allows diversification by providing redundancy: one gene can mutate and lose its original function without harming the organism.


This is a diagram showing mutations in an RNA sequence. Figure (1) is a normal RNA sequence, consisting of 4 codons. Figure (2) shows a missense, single point, non silent mutation. Figures (3 and 4) both show  frameshift mutations , which is why they are grouped together. Figure 3 shows a deletion of the second base pair in the second codon. Figure 4 shows an insertion in the third base pair of the second codon. Figure (5) shows a repeat expansion, where an entire codon is duplicated.


An  evolutionary tree  of  eukaryotic  organisms, constructed by the comparison of several  orthologous gene  sequences


The  common fruit fly  ( Drosophila melanogaster ) is a popular  model organism  in genetics research.


Schematic relationship between  biochemistry , genetics and  molecular biology


Colonies  of  E. coli  produced by  cellular cloning . A similar methodology is often used in  molecular cloning .


Boris Karloff  in  James Whale 's 1931 film  Frankenstein , based on  Mary Shelley 's 1818  novel .  The monster  is created by an unorthodox scientific experiment.


The 1953 discovery of the  double helix  chemical structure of  DNA  transformed  genetics  and launched the science of  molecular biology .


H. G. Wells 's  1896  The Island of Dr Moreau  imagined the use of  hybridisation  to create  human-like hybrid beings .


Steven Spielberg 's 1993 film  Jurassic Park  portrayed the recreation of  dinosaurs  from cloned fossil DNA.


1921 conference logo, depicting  eugenics  as a tree uniting many fields


Genome-wide CRISPR/Cas9 Knockout Screens: Workflow Overview. 1. sgRNA Library Creation: sgRNAs are computationally designed, synthesised, amplified by PCR, and cloned into a vector delivery system. This can be skipped by obtaining a commercially available library. 2. Screen: Cells are transduced with lentiviral particles containing the sgRNA library, Cas9, and other necessary components. Cells may be transduced in bulk (pooled screen), or in individual wells (arrayed screen). 3: Measurement & Analysis. Desired clones are selected and DNA is extracted. In a pooled screen, DNA sequencing will be necessary. sgRNAs are recovered, analysed, and associated genes identified.


The CRISPR-Cas9 gene editing mechanism. Cas9 cleaves dsDNA upstream (5') of the PAM site (red), and the gRNA provides a template for repair.


Producing Infectious Transgenic Lentivirus: A Simple Schematic. Two transfer plasmids, encoding Cas9 and sgRNA separately, may be used depending on the applied library.


Similar genotypic changes may result in similar phenotypic alterations, even across a wide range of species. [ 1 ]


De  Albina  y Español,  Torna atrás . Attributed to  Juan Patricio Morlete Ruiz  (1701-1770) In  casta  paintings, "torna atrás" described mixed-race individuals who expressed phenotypes dissimilar to their parents. In this painting, the daughter and mother are both of partial  Sub-Saharan  and European ancestry, yet have noticeably differing phenotypes.


A very simple genotype–phenotype map that only shows additive pleiotropy effects.


Haploinsufficiency model of dominant genetic disorders.   A +  is a normal allele.   A −  is a mutant allele with little or no function.  In haplosufficiency (most genes), a single normal allele provides enough function, so  A + A −  individuals are healthy.  In haploinsufficiency, a single normal allele does not provide enough function, so  A + A −  individuals have a genetic disorder.


Animation of the structure of a section of  DNA . The  bases  lie horizontally between the two spiraling strands.  Nitrogen : blue,  oxygen : red,  carbon : green,  hydrogen : white,  phosphorus : orange.


The typical normal human fetal cell will divide between 50 and 70 times before experiencing senescence. As the cell divides, the telomeres on the ends of chromosomes shorten. The Hayflick limit is the limit on cell replication imposed by the shortening of telomeres with each division. This end stage is known as  cellular senescence .


Punnett square : If the other parent does not have the recessive genetic disposition, it does not appear in the  phenotype  of the children, but on the average 50% of them become carriers.


Punnett square: If both parents are carriers, on the average 25 % of the offspring have the recessive trait in phenotype and 50 % are carriers.


The mother is a carrier of the recessive hereditary disposition for  Color blindness . The Y chromosome of the father cannot oppose this. The healthy allele on the X chromosome of the father can compensate for this in a daughter. She can see normally, but she becomes a conductor. The same pattern of inheritance applies to  Haemophilia .


Inheritance by female carriers


Heredity of phenotypic traits: a father and son with  prominent ears  and crowns.


DNA  structure.  Bases  are in the centre, surrounded by phosphate–sugar chains in a  double helix .


Aristotle's model of inheritance . The heat/cold part is largely symmetrical, though influenced on the father's side by other factors, but the form part is not.


Table showing how the genes exchange according to segregation or independent assortment during  meiosis  and how this translates into Mendel's laws


An example pedigree chart of an autosomal dominant disorder


An example pedigree chart of an autosomal recessive disorder


An example pedigree chart of a sex-linked disorder (The gene is on the  X chromosome .)


A three-domain  tree  of life showing the separation of  Bacteria ,  Archaea , and  Eukaryote  domains. See  Microorganisms  article for further explanation.


Tree Based on the Median Tree Algorithm. [ 11 ]  Branches with  bootstrap  (statistical) scores less than 50% were collapsed. The three domains of life are (A) archaea, (B–J) bacteria, and (K) eukaryote. Species are labeled with different colors based on their inferred HGT rates: red, >4%; yellow, 3–4%; pink, 2–3%; blue, 1–2%; green, <1%. Taxonomy labels are (A)  Euryarchaea , (B)  Proteobacteria , (C)  Chlamydiae , (D)  Spirochaetes , (E)  Thermotogae , (F)  Aquificae , (G)  Actinobacteria , (H)  Deinococcus , (I)  Cyanobacteria , (J)  Firmicutes , and (K)  Fungi .


He Jiankui


Two species mate resulting in a fit hybrid that is unable to mate with members of its parent species.


Closely related  Heliconius  species


DNase I hypersensitive sites  within chromatin [ 1 ]


World Map of populations of Khmer Diaspora              Cambodia      + 1,000,000      + 100,000          + 10,000      + 1,000      + 100


Ancient Khmer script


Map of South-east Asia showing Cambodia's territorial expansion from 1290 A.D. to present-day


Angkor Wat  in the 1900s


Upper class Khmer women in the 1800s.


Khmer dancers at Angkor Wat, 1920s.


Protein and RNA are transported in particles (white dots) from the nurse cells (maternal) to the developing oocyte in  Drosophila melanogaster . Scale bar shows 10 μm.


A stalk-eyed fly


DNA strand slippage during replication of an STR locus. Boxes symbolize repetitive DNA units. Arrows indicate the direction in which a new DNA strand (white boxes) is being replicated from the template strand (black boxes). Three situations during DNA replication are depicted. (a) Replication of the STR locus has proceeded without a mutation. (b) Replication of the STR locus has led to a gain of one unit owing to a loop in the new strand; the aberrant loop is stabilized by flanking units complementary to the opposite strand. (c) Replication of the STR locus has led to a loss of one unit owing to a loop in the template strand. (Forster et al. 2015)


A partial human STR profile obtained using the  Applied Biosystems  Identifiler kit


Consensus   neighbor-joining  tree of 249 human populations and six chimpanzee populations. Created based on 246 microsatellite markers. [ 65 ]


Short Tandem Repeat (STR) analysis on a simplified model using  polymerase chain reaction  (PCR): First, a DNA sample undergoes PCR with  primers  targeting certain STRs (which vary in lengths between individuals and their  alleles ). The resultant fragments are separated by size (such as  electrophoresis ). [ 74 ]


A number of DNA samples from specimens of  Littorina plena  amplified using polymerase chain reaction with primers targeting a variable simple sequence repeat (SSR, a.k.a. microsatellite) locus. Samples were run on a 5% polyacrylamide gel and visualized using silver staining.


Through the insertion of multiple genes and telomeres, a shortened minichromosome is produced, which can then be inserted into a host cell


(A)  Transposable elements  are flanked by inverted  tandem repeats  (TIRs). (B)  Transposases  cleave the transposable element at the TIRs. The free transposable element inserts into another part of the  genome .


Bacterial conjugation . (1) Production of  pilus . (2) Pilus connects two  bacteria . (3) One strand of  plasmid   DNA  moves into the recipient. (4) Both bacteria contain identical plasmids.


Visualization of genetic modification with a piece of DNA being removed by tweezers [ citation needed ]


Image depicts the CRISPR genome editing proc.


Common products of genetic engineering


Image: example of karyotyping showing a total of 46 chromosomes in the genome.


FISH images of chromosomes from dividing orangutan (left) and human (right) cells. Yellow probe shows 4 copies of a region in the orangutan genome and only 2 copies in human.


A cell containing a rearrangement of the bcr/abl chromosomal regions (upper left red and green chromosome). This rearrangement is associated with chronic myelogenous leukemia, and was detected using FISH.


Tulip flower showing mosaicism


Frequency distribution of mtDNA haplogroup Z in Eurasia


Older man from Faridabad, Haryana, India


(a)  The survival rate within a population decreases with age, while the reproduction rate remains constant.  (b)  The reproduction probability peaks early in life, at sexual maturity, and then steadily decreases as an individual ages, with the remaining share of the population decreasing with age as they enter the  selection shadow .


Neofunctionalization is the process by which a gene acquires a new function after a gene duplication event. The figure shows that once a gene duplication event has occurred one gene copy retains the original ancestral function (represented by the green paralog), while the other acquires mutations that allow it to diverge and develop a new function (represented by the blue paralog).


Areas of focus in neurogenomics. This figure highlights the different sources of data and areas of research that guide the field of neurogenomics.


A typical network analysis pipeline in neurogenomics


Examples of markers that are expressed in different stages of neurogenesis in adult hippocampus.


RNA in situ hybridization - KRT5 and housekeeping gene in human melanoma FFPE tissue section - visualized under brightfield and fluorescence microscope


Mouse brain  slice stained by Immunohistochemistry.


Each circle represents a functional gene variant and lines represents point mutations between them. Light grid-regions have low  fitness , dark regions have high fitness. ( a ) White circles have few neutral neighbours, black circles have many. Light grid-regions contain no circles because those sequences have low fitness. ( b ) Within a neutral network, the population is predicted to evolve towards the centre and away from ‘fitness cliffs’ (dark arrows).


A simple genotype–phenotype map.


Regulation of nickel ion uptake by components of the  nik  operon


Meiosis I Meiosis II Fertilization Zygote  The left image at the blue arrow is nondisjunction taking place during meiosis II. The right image at the green arrow is nondisjunction taking place during meiosis I. Nondisjunction is when chromosomes fail to separate normally resulting in a gain or loss of chromosomes.


Nondisjunction of sister chromatids during mitosis:     Left:  Metaphase of mitosis. Chromosome line up in the middle plane, the mitotic spindle forms and the kinetochores of sister chromatids attach to the microtubules.    Right:  Anaphase of mitosis, where sister chromatids separate and the microtubules pull them in opposite directions.   The chromosome shown in  red  fails to separate properly, its sister chromatids stick together and get pulled to the same side, resulting in mitotic nondisjunction of this chromosome.


Karyotype of X monosomy (Turner syndrome)  This condition is characterized by the presence of  only one X chromosome  and no Y chromosome (see bottom right corner).


Karyotype of trisomy 21 (Down syndrome)  Note that chromosome 21 is present in 3 copies, while all other chromosomes show the normal diploid state with 2 copies. Most cases of trisomy of chromosome 21 are caused by a nondisjunction event during meiosis I (see text).


Loss of a tumor suppressor gene locus according to the two-hit model :   In the first hit, the tumor suppressor gene on one of the two chromosomes is affected by a mutation that makes the gene product non-functional. This mutation may arise spontaneously as a DNA replication error or may be induced by a DNA damaging agent. The second hit removes the remaining wild-type chromosome, for example through a  mitotic nondisjunction  event. There are several other potential mechanisms for each of the two steps, for example an additional mutation, an unbalanced translocation, or a gene deletion by recombination. As a result of the double lesion, the cell may become malignant because it is no longer able to express the tumor suppressor protein.


Agrobacterium tumefaciens  (A) targets the nucleus of a plant cell (D) during an infection.


Diagram showing the reduction in number of the  chromosomes  in the process of maturation of the  ovum . (In mammals, the first  polar body  normally disintegrates before dividing, so only two polar bodies are produced. [ citation needed ] )


Oogenesis in eukaryotic cells. (A) oogonium where the mitotic division occurs (B) differentiation and meiosis I begins (C) primary oocyte (D) meiosis I is completed and meiosis II begins (E) secondary oocyte (F) first polar body (G) ovulation must occur and the presence of the sperm penetration (fertilization) induces meiosis II to completion (H) ovum (I) second polar body


Oogenesis throughout a woman's life


Diagram of oogenesis in a  digenean  ( Platyhelminthes )


Illustration of the degree of penentrance


Illustration of different degrees of penetrance and variable expressivity


Illustration of BRCA1 and BRCA2 mutations and cancer risk. [ 8 ]


Illustration of epigenetic related methylation of histone tail. Giving cause to alterations.


Location of human  PGLYRP3  gene on chromosome 1 and schematic gene, cDNA, and protein structures with exons, introns, and protein domains indicated.


Location of human  PGLYRP4  gene on chromosome 1 and schematic gene, cDNA, and protein structures with exons, introns, and protein domains indicated.


Chocolate-colored male Himalayan rabbit


Phenotypic Integration is important for many traits.  One specifically is the development of fewer bones in the neurocranium.


Northwestern Garter Snake's color patterns and escape mechanisms are integrated.


The Poison Dart Frog is an example of a species that illustrates phenotypic integration.


Phenotypic plasticity is the ability of one genotype to produce more than one phenotype when exposed to different environments. Each line here represents a genotype. Horizontal lines show that the phenotype is the same in different environments; slanted lines show that there are different phenotypes in different environments, and thus indicate plasticity.


Phenotypic plasticity of sorghum flowering time evaluated from seven environments. The identified  photothermal time , a performance-independent index, quantifies the relevant environmental input and enables a systematic framework for modelling, explaining, and predicting phenotypic values under natural conditions. [ 6 ]


Hatch rates for red-eyed tree frog tadpoles depends on predation


Certain transcripts contain poison exons that can be incorporated via alternative splicing. Skipping of the poison exon leads to a productive transcript that is translated to protein. Incorporation of the poison exon introduces a premature termination codon into the transcript that leads to degradation of the transcript via nonsense-mediated decay. (PDB: 2N3L)