Arctic bacteria help find life on Jupiter's Icy Moon

Arctic bacteria help find life on Jupiter`s Icy Moon Washington: It is not easy to search for life on one of Jupiter’s icy moons: Europa as just getting there can be a problem.

Thus, scientists would love to find a place on Earth that resembles the sulfur-laden surface of Europa. And now they have.

In a fjord in Canada scientists have found a landscape similar to Europa. It consists of a frozen and sulphurous environment, where sulphur associated with Arctic bacteria offer clues for the upcoming missions in the search for traces of life on Europa.

It is not easy to find a place on Earth where ice and sulphur come together, supposedly like on Europa, Jupiter's moon. Nonetheless, this place has been located at Borup Fjord Pass in the Canadian High Arctic. Here the sulphurous yellow emissions contrast with the whiteness of the environment, creating images similar to those captured at Jupiter's satellite.

US researchers have now verified that the sulphur involved in the life cycle of Arctic microorganisms has some characteristics that could help to detect biological remains on Europa.

Large space agencies like NASA and the European Space Agency are already in the process of preparing missions.

“We have discovered that elemental sulphur (S) can contain morphological, mineralogical and organic ‘biosignatures’ linked to bacterial activity. If they are found on Europa, this would suggest the possible presence of microorganisms,” as explained to SINC by Damhnait Gleeson, lead author of the study and currently member of the Centro de Astrobiologia (INTA-CSIC, Spain).

The ''biosignatures'' are associated with needle and rhomboid sulphur shapes in which mineralised remains of microorganisms and extracellular material appears.

Thanks to electron microscopy and X-ray diffraction techniques, the formation of a rare type of sulphur has also been observed in association with organic components: the rosickyite.

What is more is that small quantities (parts per million) of protein, fatty acids and other biomolecules have appeared in the sulphurous material.

"There is much evidence of bacterial activity," highlighted Gleeson, who wonder if in the Europa's icy crust, or the ocean or lakes supposedly beneath it, there could be a similar microbial community that uses sulphur as their source of energy.

The study has been published in the Astrobiology journal.


Friday, Oct. 2: Jaycee Dugard's kidnapping

The kidnapping and the rescue of Jaycee Dugard, 18 years after the crime, stunned the nation this past summer, leaving many to ask why wasn't the alleged kidnapper caught sooner and how could there have been so many missed opportunities. Now, Dateline investigates and brings viewers up to date on the latest developments on the case. NBC's Keith Morrison reports. See it Friday at 9 p.m. ET, 8 p.m. CT.


Lenski’s new results; Behe’s red herring

Richard Lenski is an evolutionary biologist who studies evolution by analyzing changes in bacterial populations.  Perhaps he is most famous for his long-term experiment where his group identified a population that evolved to use a nutrient (citrate) that E. coli normally can’t use.  This was a very important finding as it provided proof-of-concept that random mutations alone are sufficient to induce new functions.

In a recently published paper in Nature, Lenski takes the above experiment and analyzes the frequency of mutation throughout these populations.  The goal of this paper was not to show which specific mutations led to the ability of the bacteria to use the new nutrient source.  The goal was to look at the level of overall mutation rate during the experiment.  In the authors own words:

The relationship between rates of genomic evolution and organismal adaptation remains uncertain, despite considerable interest.

Thus, the coupling between genomic and adaptive evolution is complex and can be counterintuitive even in a constant environment. In particular, beneficial substitutions were surprisingly uniform over time, whereas neutral substitutions were highly variable.

Of course the Discovery Institute and ID proponents are not going to keep quiet about any work coming from Lenski’s lab as their work provided such an important part of the evolutionary puzzle.  Michael Behe took up the challenge this time and wrote an entry at Evolution News and Views.  Lets address some of Behe’s points.

Behe’s first compliant is that

[Lenski's group] identified a couple score of mutations which they say are likely beneficial ones. That is almost certainly true, but what they don’t emphasize is that many of the beneficial mutations are degradative — that is, they eliminate a gene or its protein’s function.

First, Behe is attacking the paper for something that is really irrelevant to the point of the paper.  It also doesn’t disprove the original result of that spontaneous mutations that led to a novel attribute.  It is a red herring designed to poke holes in Lenski’s work instead of directly arguing against it.  So why all the degradative mutations?  Well, these experiments were done in a lab under strict conditions (single temperature, no other organisms, defined nutrients) to eliminate other variables. Without these other stimuli, is it any wonder that most changes are degradative?

Behe also criticizes the rise in what is called a mutator line in these experiments.  A mutator strain is one in which mutations arise more frequently than in a normal strain.  Again this doesn’t really address the ideas of the new paper or in the proof-of-concept of Lenski’s original data.

Anyway, who cares that these strains became mutator strains. A mutator just increases the frequency by which mutations arise. Maybe it would have taken 3 times as long for the beneficial mutation to arise if the mutator strain hadn’t evolved. It doesn’t change the fact that the cells evolved into a state where they could use a nutrient that they couldn’t before.   Besides, it is a moot point as one of the original mutation had arose before the 20,000 generation, a time before the mutation that led to mutator strain had occurred.

Finally, Behe closes with the expected tactics that we have grown to love from ID proponents.  The first tactic as illustrated above is to wrongfully criticize valid experiments in favor of evolution.  The second tactic is then to say how this data really proves intelligent design:

Lenski’s decades-long work lines up wonderfully with what an ID person would expect — in a huge number of tries, one sees minor changes, mostly degradative, and no new complex systems. So much for the power of random mutation and natural selection.

First, an ID proponent would not expect the E. coli to ever use the new nutrient.  The “power of random mutation and natural selection” led the bacteria to a whole new attribute.  Don’t forget, this experiment lasted only decades, or 1/100,000,000 the time bacteria are believed to inhabit the earth.  Finally, like I stated above, these were very unnatural conditions that would never be experienced during normal life on earth.

Michael Behe compares apples to oranges while waiting for two mutations

Plasmodium malariae

Plasmodium malariae

A recent scientific article published in Genetics criticized Michael Behe and “exposed flaws” in his thinking.  The article in question, Waiting for Two Mutations: With Applications to Regulatory Sequence Evolution and the Limits of Darwinian Evolution, provides a mathematical model of the rate for two different mutations to occur in order.  They show that the time for prespecified mutations is within reason and support this by using two real world examples from humans and fruit flies.  Behe doesn’t believe it.

Behe had previously calculated the mutation rate that makes the protozoan P. falciparum (causes malaria) resistant to the antibiotic chloroquine that arose from two prespecified mutations in one protein.  He argued that this would take 1,000,000,000,000,000 years to achieve a similar pair of mutation in humans based on human population numbers and age until reproduction.   He seems to think that this is evidence to support intelligent design.

There are several problems with Behe’s thinking.  The most obvious is that Behe is comparing completely different organisms.  The mutation rate between various organisms can be very different.  In writing this post, I quickly determined from following the links from Wikipedia that the error rate of other protozoan (not specifically P. falciparum) seems to be around 100 fold lower than humans.  Not exactly the best comparison is it?

Other errors in Behe’s thinking include

  • Behe calculated the requirement for prespecified mutations; Evolution is not prespecified
  • These mutations could have arisen many times without our knowledge.  Unless Behe knows the sequence of every single P. faciparum, he can not really know how often these mutations occurred
  • Behe’s calculations seem to make the common statistical error of treating two consecutive events as one event.  For example, the odds of a couple that already have two girls having another girl is still 1 in 2, not 1 in 8 like you would get if you asked what are the odds in the beginning of having 3 girls

The original authors had many other complaints against Behe’s assessment, but they are fairly technical and beyond the scope of this blog.  If your interested, follow the links below.  Even without these criticisms, it is clear that Behe’s mind is being clouded over by the motivation of having an intelligent designer.

One interesting thing to note is that the authors actually call out Michael Behe by name in the abstract. I actually think this is semi-unprofessional. At the same time however, I think it also shows a lot of gumption. They must have known that not only would Behe respond with sharp criticism.

Further reading:

Behe’s blog

Behe’s response to Rick Durrett and Deena Schmidt

Durrett and Schmidt’s response to Behe’s response

Waiting for Two Mutations

Behe’s 2007 paper on the subject

Flock of Dodos: The Intelligent Design – Evolution Circus

Randy OlsenAfter waiting patiently for it to reach the top of my Netflix cue, I recently watched Randy Olsen’s “Flock of Dodos”.  Although I haven’t seen Expelled yet, I believe “Flock of Dodos” is its antithesis.  Randy Olsen, PhD is a trained marine biologist and former tenured professor, while Ben Stein was a political speech writer and professor of law.  Right from the start, you can see that one side is treating the evolution/intelligent design debate coming from the side of science and the other from the side of politics. Presumably, Stein would say that his film comes from an outsiders perspective so he is able to present an unbiased opinion.

Olsen does a good job giving both sides of the debate their fair share of time.  He even interviews Michael Behe, one of the superstars of Intelligent Design, and lets him speak freely.  Of course the pro-evolution proponents are plentiful.  He even brings together a group of evolutionary biologists to play poker and discuss Intelligent Design.  He also covers much of the Kansas school board debacle and the Dover, PA trial.

The movie has a light and cheerful feel, which was obviously intentional yet appreciated. So many documentaries, even highly acclaimed ones, are outright boring. Olsen achieves this feeling by sprinkling in amusing cartoons, colorful anecdotes, and of course lightly mocking people.  He even introduces us to his mother, Muffy Moose, who appears that she needs a movie or two of her own.  The “dodos” Olsen is referring to are not just Intelligent Design proponents.  He makes a point to say that the scientists who do not combat attacks evolutionary theory are as much dodos as anyone.

One of the things that I really appreciated about the movie was the way that Olson made fun of the idea of Intelligent Design. In particular, he and his interviewees mockhow badly some things were designed. The worst example of intelligent design (or the best example of unintelligent design) was digestive system of rabbits. Apparently, rabbits have their fermentation organ (where the complex plant material is digested) at the very end of their digestive system. In order for the rabbits to fully digest a meal, it has to eat its own poop. Behold: Intelligent! Design!

Olson makes the comment during the movie that when scientists try to share their side of the story, they are talking above the general audience. Not completely their fault as most have been working in their area of expertise most of their lives, and therefore they have a hard time bringing the conversation to a lower level. However, I think the problem is even worse than Olson believes. The target audience of the documentary was you average person, but one of the people who watched the documentary with me was a little lost. After all, she said she stopped learning about biology during “leaf collecting.” This leads me to believe that our educations system may be lacking, but that is a subject of another post.

My general feeling after finishing the movie, is that there is a war of ideas, where the two sides are playing by different rules.  The evolutionists are using facts and evidence, while Intelligent Design proponents are using catch phrases and religious appeal.  Intelligent design proponents are not evil or malicious (for the most part). In fact, most in the movie came across as being honest, caring, and kind-hearted. These attributes could be part of the problem because they are a little too nice, a little too naive, and a lot too trusting.

So for those of you interested in the Evolution / Intelligent Design debate, I recommend that you see this movie.

The evolutionary numbers game

In my last post, I brought up how Michael Behe used the fact that 40,000 generations of E. coli were necessary for Richard Lenski’s experiment to find an E.coli who could utilize citrate. In this post, I am going to run through some numbers to show how 40,000 generations is nothing to evolutionary time.  Of course my numbers are going to be rough estimates, but I think it will get the job done.

For the sake of argument, lets say the earth is 10,000 years old (yes, people do believe the earth is this young). If Behe’s math is correct, then E. coli have 2,000 generations a year or 20,000,000 generations over the time of the young earth. More realistically, the earth is 4.5 billion years old, or nearly 10 trillion generations of E. coli. Of course E. coli hasn’t been around the whole time the earth has, but it does put that 40,000 number into perspective.

Let’s say that a beneficial mutation, such as the ability to use citrate, occurs once every 100,000 generations. Given the 10 trillion number above, that would give 100,000 beneficial mutations. Keeping in mind that E. coli only has ~5000 genes, each gene could have changed 20 times.

The last set of numbers we will be addressing is the nearly unfathomable number of bacteria on the planet.  For reference, our bodies alone are estimated to have 1,000 trillion or 10^15 of bacteria (not all E. coli of course) of bacteria (Yes, I know, it is kind of gross). There are over 6 billion people on earth bringing the total of bacteria inside humans to 6 X 10^24.

Now that is a lot of bacteria, just inside people, but how about all over the planet?  Bacteria are everywhere: inside us, on practically every surface, throughout the ocean, and throughout the earth.  It has been estimated that there are 5 X 10^30 bacteria on earth.

10^12 generations of bacteria and 10^30 bacteria.  Those are mind-boggling numbers!  I know the numbers don’t really mean too much by themselves, but just keep them in mind when an IDer tries to convince you that something like 40,000 generations is a big deal.

Behe Doesn’t Believe in Evolution in a Tube

Michael Behe writes on June 6th a post entitled: Multiple Mutations Needed for E. Coli. This post came from his amazon blog, where he is trying to push his book. Behe is writing of course about Richard Lenski’s (et al.) recent publication in PNAS (Proceedings of the National Academy of Sciences). In the article, the authors describe an experiment that has been going on since 1988. Now that is persistence! Richard Lenski is the principal author and has kept the same 12 cultures of E. coli reproducing for the last 20 years. These cultures are grown in two food sources: glucose, which E. coli readily uses and citrate, which E. coli cannot use. After nearly 32,000 generations, one of the E. coli cultures developed, or evolved, the ability to use citrate.

This experiment provides an example of a living organism evolving a new trait in the tightly controlled setting. This type of result had not really been seen before (largely due to the long times necessary) and was something of a missing piece of evidence for evolution. Evolutionary type changes have been observed outside of the lab (isolated lizards, nylon eating bacteria), but not in a true experimental setup.

The changes in the isolated cultures of E. coli were not limited to the ability to utilize citrate. They also exhibited changes from the original cultures that include:

higher maximum growth rates on glucose, shorter lag phases upon transfer into fresh medium, reduced peak population densities, and larger average cell sizes relative to their ancestor.

10 of the 12 E. coli cultures also “evolved increased DNA supercoiling.” When challenged with other carbon sources, such as maltose or lactose, their growth rates differed. These changes are indeed important to keep in mind as more evidence of evolutionary change, but the clear advantage of the gain-of-function change illustrated by the new ability to utilize citrate is monumental.

Predictably, Behe does not seem to be too impressed by the experiment. He makes the point that E. coli divides rapidly and 20 years equates to 40,000 (even though the paper clearly states 31,500) generations and therefore is not that remarkable. This may seem like a lot of generations, but 20 years is not even a blink of the eye in evolutionary timescales. I will give an in depth analysis of the numbers in a later post. Besides, this experiment provides proof of concept that random mutations can lead to a gain-of-function change, one of evolution denier’s talking points, as Casey Luskin as said: “ID is far more interested in explaining the GAIN of biological function rather than loss of function.”

Lenski wanted to further explore how the E. coli were able to gain the ability to use citrate. Was it a single mutation event or was it a series of mutations? In order to determine which was true, he repeated the experiment with cultures that had gone through various numbers of generations, 12 in all. He found that when he took cultures after 20,000 generations, they more quickly were cit+. This led Lenski to conclude that there were multiple mutational events leading to cit+, one of which occurred before the 20,000 generation. An important finding, and one that shows that there can be silent, but beneficial, mutations. Behe disagrees:

I am not sure how someone so educated and respected could say something so completely vacuous. In evolution, everything is carried over, whether it has an immediate benefit or not. Maybe one of the mutations that occurred allowed the mutant cell to grow slightly faster than the others. Maybe the mutation was silent and did not help or harm anything. Does Behe really believe that every mutation has to have a large phenotypic effect to be in accord with evolutionary theory?

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Energy makes the world go round.  It’s something that is palpable and drives us to move forward in our lives.  Every system needs energy.  Every organization needs energy.  I had an experience last night that made me think about how organizational energy translates to personal energy, and in turn health and healing.

I attended a meeting of the art guild that I belong to, a textile arts guild.  The organization has about 275 members and has been in existence for twenty-four years.  Like many organizations there is an old guard, those who founded the organization or have been members for over twenty years.  These were the original leaders of the group and shaped the path of the organization.

I had been the President of the organization for two years and during that time I was always conscious about not only the energy at the meeting, but how to keep the energy level high and people engaged between meetings.  My monthly President’s message in the newsletter were meant to get members thinking, not only about the organization, but their role in the organization, and where they fit in the great world of art.

Last night I attended the meeting after a five-month hiatus (I’d been working in Tennessee).  The meeting was “fine”.  I don’t believe that “fine” is a compliment.  It’s just a comment on the meeting moving along.  Even the speaker was less than dynamic.  I was hoping to get re-energized after the five-month hiatus.  The only thing I was energized by were the moments when I reconnected with friends I hadn’t seen in a long time.

So how does that translate to your own health and healing?  What do you get excited about?  What keeps you engaged in your life and your healing journey?  How do you generate excitement for yourself to keep learning, continue experimenting, and design a life that will leave you with no regrets at the end of your life?

Energy is palpable.  It’s a force that is in you and around you.  Energy is what the body needs to heal.  Energy allows you to be tenacious in your healing journey.  It’s the momentum we need to tackle the challenges faced with any health challenge.

How do you experience energy in you and around you?  What happens when your energy level is less than optimal?  Are you sensitive to energy levels in others, even in groups and organizations?  How will you check your energy gauge and keep it above empty?

You’re going to think I’m a bit strange because the story I’m going to share is about my dog.  Believe it or not, my dog Tashi has had more medical problems than most of us will have in our own human lives.

It all started about five or six years ago when she acquired Methicillin-resistant Staphylococcus aureus (MRSA).  I don’t know how she acquired this infection, but it has been recurring relentlessly over the years.  Unfortunately MRSA isn’t curable, it becomes a chronic, potentially life-threatening condition.

The incident this past week started last Wednesday when Tashi awoke limping.  Her back foot (location of the MRSA wound) was swollen.  She ate breakfast and took her place in the family room and didn’t move for seven hours.  We decided to take her to the emergency vet that evening because she wasn’t engaging in normal activities and she couldn’t get up off the floor on her own.

The vet we saw, a young vet, was quite personable and very good with Tashi.  He did a thorough exam and was respectful of her pain limits.  The thing that caught my attention was his personal shock at how swollen her foot and leg had become.  He was perplexed hoping that maybe she had an issue with a bone or joint.  Because of the MRSA he had to be very careful about any biopsy or culture because he didn’t want to spread the MRSA if in fact it was present.

The radiograph didn’t show any abnormalities, a huge relief.  He did perform a culture of the wound on her foot, non-invasive.  He also prescribed a very strong antibiotic and pain medication.  We took her home with the hope that  she would begin the healing process.

Unfortunately as Thursday progressed, her leg became more swollen and this was worrisome.  The next step was to take her to her regular vet.  One more appointment and when he saw her foot he was also a bit perplexed and concerned.  She wasn’t putting pressure on her foot and the leg was swollen up to her hip.  He prescribed a second antibiotic and now we wait for the culture results.

The sad part is that animals can’t tell us other than behavior about their physical problems.  I feel fortunate to have medical professionals that are engaged in her well-being and take measures to create increased odds at healing the infection.  I didn’t know that the field of veterinary medicine doesn’t have a specialization in infectious disease.  The specialty seems to be on the horizon, but until that happens either a general practitioner, or in Tashi’s case her dermatologist/allergy doctor have to serve as our medical resource.

How does this translate into the experience of humans?  We don’t always have an answer for symptoms that arise from an illness.  It’s important to feel comfortable going to a specialist if you don’t feel that your illness/symptoms are getting better.  In addition, I felt it important for her regular physician to see her because he knows her history and her body.  He understands her response to past medications and infections.  He knows her temperament and tuned into her response when he exams her.  These are important because her history may have clues to heal the current medical dilemma.

Things are still uncertain and the fact that she’s over twelve years old doesn’t soothe my anxiety.  I can see the desire in her eyes to get better (my personal projection) but I’m hoping we make it through this health crisis.  I hope you maintain that fire in your soul to get better or well.

I have to admit that when it comes to television; I’m hooked on reality shows related to singing and dancing.  I’ve been watching NBC’s The Voice, and they are down to the final four.  These four are competing for a record contract, and of course, fame.  What I like about this show is that they don’t have an age limit, so it’s really about the talent, not the teenybopper vote.

I’ve heard Anderson Cooper confess that he’s a reality television junkie.  I guess when you cover tragedy all over the globe; reality television is a break from reality.  So why do we need to escape from reality?

Those of you who have been diagnosed with a chronic or life-threatening illness know how hard life can be since the diagnosis.  It makes you wonder how much more real can you get than living your life filled with doctors appointments, lab tests, and trips to the pharmacy.  Being in your body is as real as it gets, so why don’t you have your own reality television show?

It’s interesting how illness can be a storyline on a television show, but not the focus of the show.  Obviously there have been illness specific movies or theater productions focusing on illness such as WIT or The Diving Bell and the Butterfly, but no network or cable show focusing on the reality of real life illness.

I’m grateful when actors such as Michael J. Fox are guests on talk shows because he discusses the reality of living with illness.  He gives an unfiltered account of his life with Parkinson’s disease, and how he prepares himself when he has to go to work.  That’s as real as it gets!

Everyone in life has some type of struggle, but illness poses unique challenges.  It impacts not only you but also your family.  It can physically separate you from others, more out of fear and ignorance than from malicious intent.  You’re often misunderstood because throughout the day your life may revolve around other things than going to the grocery store and picking up the kids from soccer.  It’s multifaceted and often feels like a tightrope act.

When you’re watching reality television, please give yourself credit for living a life that is more real and more important than any program on television.  Become the success you are striving for and that will prevent you from being voted off the island!

Lessons from Bella

I have two dogs and both have had their fair share of medical issues.  I’ve talked much more about my black lab Tashi who has suffered with recurrent infections due to MRSA.  I’ve learned a lot about facing illness and creating a new normal from her.  This past weekend my other dog, Bella, visited the vet because of a cyst in her ear.

As it turns out, Bella has a hematoma in her ear.  It was drained and a cortisone injection to reduce the swelling was administered.

During the examination the doctor noticed Bella required dental work with the probability that a tooth would need to be pulled.  If that weren’t enough, she has a cyst in the middle of her head that we decided is she’s going to be under anesthesia should probably be removed.

Bella was sent home with a bandage covering her ear.  Unfortunately, she kept trying to remove it so we had to get one of those big radar dishes for her head.  The poor thing was bumping into walls, tripping over things, and was generally a bit disoriented.

This morning I took Bella to the bet for her procedure.  She was very good in the exam room, probably because she was scared.  She began to shiver.  Her anxiety was evident and trying to console her did little good.  The vet was very good with her and he too tried to console her.  So why am I talking about a 10-1/2 year old dog?  Because dogs don’t understand their pain, the medical procedures they endure, or adjusting to medical devices for their own protection.

On the other hand, as humans we also don’t understand pain, medical procedures, or medical devices that become part of our every day lives.  Too many of us try and make sense of our illnesses, but is that even possible?

When we enter the medical arena we often try and hide our fear and anxiety, but it still always comes through.  Because illness is so disorienting how do we try and alleviate the panic?  It’s important to have people in your life that will help you disperse the anxious energy.  Talking, engaging in creative activities, finding a spiritual director, illness coach, or psychotherapist helps with those anxious moments.

What would happen if you really experienced the anxiety so you could disperse it into the universe?  We expend so much energy trying to hide it or suppress it that we are continually exhausted physically, emotionally, and spiritually.  I had a clinical supervisor who said, “You can’t get out of something if you’re never in it”.  It’s like dancing around the mouth of the volcano…sometimes you have to jump in so you can know what you’re getting out of, experientially.

My dogs are my examples for coping with illness.  They seem fearless, truly a projection.  They provide me with insights into the illness experience that I wouldn’t have made conscious any other way.  It is because of that, that I am eternally grateful and I make sure any way I can be of service to them I will.

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1.  Orthologous Gene Clusters and Taxon Signature Genes for Viruses of Prokaryotes
Journal of Bacteriology  2013;195(5):941-950.
Viruses are the most abundant biological entities on earth and encompass a vast amount of genetic diversity. The recent rapid increase in the number of sequenced viral genomes has created unprecedented opportunities for gaining new insight into the structure and evolution of the virosphere. Here, we present an update of the phage orthologous groups (POGs), a collection of 4,542 clusters of orthologous genes from bacteriophages that now also includes viruses infecting archaea and encompasses more than 1,000 distinct virus genomes. Analysis of this expanded data set shows that the number of POGs keeps growing without saturation and that a substantial majority of the POGs remain specific to viruses, lacking homologues in prokaryotic cells, outside known proviruses. Thus, the great majority of virus genes apparently remains to be discovered. A complementary observation is that numerous viral genomes remain poorly, if at all, covered by POGs. The genome coverage by POGs is expected to increase as more genomes are sequenced. Taxon-specific, single-copy signature genes that are not observed in prokaryotic genomes outside detected proviruses were identified for two-thirds of the 57 taxa (those with genomes available from at least 3 distinct viruses), with half of these present in all members of the respective taxon. These signatures can be used to specifically identify the presence and quantify the abundance of viruses from particular taxa in metagenomic samples and thus gain new insights into the ecology and evolution of viruses in relation to their hosts.
PMCID: PMC3571318  PMID: 23222723
2.  Consistent mutational paths predict eukaryotic thermostability
Proteomes of thermophilic prokaryotes have been instrumental in structural biology and successfully exploited in biotechnology, however many proteins required for eukaryotic cell function are absent from bacteria or archaea. With Chaetomium thermophilum, Thielavia terrestris and Thielavia heterothallica three genome sequences of thermophilic eukaryotes have been published.
Studying the genomes and proteomes of these thermophilic fungi, we found common strategies of thermal adaptation across the different kingdoms of Life, including amino acid biases and a reduced genome size. A phylogenetics-guided comparison of thermophilic proteomes with those of other, mesophilic Sordariomycetes revealed consistent amino acid substitutions associated to thermophily that were also present in an independent lineage of thermophilic fungi. The most consistent pattern is the substitution of lysine by arginine, which we could find in almost all lineages but has not been extensively used in protein stability engineering. By exploiting mutational paths towards the thermophiles, we could predict particular amino acid residues in individual proteins that contribute to thermostability and validated some of them experimentally. By determining the three-dimensional structure of an exemplar protein from C. thermophilum (Arx1), we could also characterise the molecular consequences of some of these mutations.
The comparative analysis of these three genomes not only enhances our understanding of the evolution of thermophily, but also provides new ways to engineer protein stability.
PMCID: PMC3546890  PMID: 23305080
Thermophily; Comparative genomics; Protein engineering; Eukaryotes; Fungi
3.  STRING v9.1: protein-protein interaction networks, with increased coverage and integration
Nucleic Acids Research  2012;41(D1):D808-D815.
Complete knowledge of all direct and indirect interactions between proteins in a given cell would represent an important milestone towards a comprehensive description of cellular mechanisms and functions. Although this goal is still elusive, considerable progress has been made—particularly for certain model organisms and functional systems. Currently, protein interactions and associations are annotated at various levels of detail in online resources, ranging from raw data repositories to highly formalized pathway databases. For many applications, a global view of all the available interaction data is desirable, including lower-quality data and/or computational predictions. The STRING database ( aims to provide such a global perspective for as many organisms as feasible. Known and predicted associations are scored and integrated, resulting in comprehensive protein networks covering >1100 organisms. Here, we describe the update to version 9.1 of STRING, introducing several improvements: (i) we extend the automated mining of scientific texts for interaction information, to now also include full-text articles; (ii) we entirely re-designed the algorithm for transferring interactions from one model organism to the other; and (iii) we provide users with statistical information on any functional enrichment observed in their networks.
PMCID: PMC3531103  PMID: 23203871
4.  PTMcode: a database of known and predicted functional associations between post-translational modifications in proteins
Nucleic Acids Research  2012;41(D1):D306-D311.
Post-translational modifications (PTMs) are involved in the regulation and structural stabilization of eukaryotic proteins. The combination of individual PTM states is a key to modulate cellular functions as became evident in a few well-studied proteins. This combinatorial setting, dubbed the PTM code, has been proposed to be extended to whole proteomes in eukaryotes. Although we are still far from deciphering such a complex language, thousands of protein PTM sites are being mapped by high-throughput technologies, thus providing sufficient data for comparative analysis. PTMcode ( aims to compile known and predicted PTM associations to provide a framework that would enable hypothesis-driven experimental or computational analysis of various scales. In its first release, PTMcode provides PTM functional associations of 13 different PTM types within proteins in 8 eukaryotes. They are based on five evidence channels: a literature survey, residue co-evolution, structural proximity, PTMs at the same residue and location within PTM highly enriched protein regions (hotspots). PTMcode is presented as a protein-based searchable database with an interactive web interface providing the context of the co-regulation of nearly 75 000 residues in >10 000 proteins.
PMCID: PMC3531129  PMID: 23193284
5.  DvD: An R/Cytoscape pipeline for drug repurposing using public repositories of gene expression data
Bioinformatics  2012;29(1):132-134.
Summary: Drug versus Disease (DvD) provides a pipeline, available through R or Cytoscape, for the comparison of drug and disease gene expression profiles from public microarray repositories. Negatively correlated profiles can be used to generate hypotheses of drug-repurposing, whereas positively correlated profiles may be used to infer side effects of drugs. DvD allows users to compare drug and disease signatures with dynamic access to databases Array Express, Gene Expression Omnibus and data from the Connectivity Map.
Availability and implementation: R package (submitted to Bioconductor) under GPL 3 and Cytoscape plug-in freely available for download at
Supplementary information: Supplementary data are available at Bioinformatics online.
PMCID: PMC3530913  PMID: 23129297
6.  MOCAT: A Metagenomics Assembly and Gene Prediction Toolkit
PLoS ONE  2012;7(10):e47656.
MOCAT is a highly configurable, modular pipeline for fast, standardized processing of single or paired-end sequencing data generated by the Illumina platform. The pipeline uses state-of-the-art programs to quality control, map, and assemble reads from metagenomic samples sequenced at a depth of several billion base pairs, and predict protein-coding genes on assembled metagenomes. Mapping against reference databases allows for read extraction or removal, as well as abundance calculations. Relevant statistics for each processing step can be summarized into multi-sheet Excel documents and queryable SQL databases. MOCAT runs on UNIX machines and integrates seamlessly with the SGE and PBS queuing systems, commonly used to process large datasets. The open source code and modular architecture allow users to modify or exchange the programs that are utilized in the various processing steps. Individual processing steps and parameters were benchmarked and tested on artificial, real, and simulated metagenomes resulting in an improvement of selected quality metrics. MOCAT can be freely downloaded at
PMCID: PMC3474746  PMID: 23082188
7.  Deciphering a global network of functionally associated post-translational modifications
This study is the first large-scale comparative analysis of multiple types of post-translational modifications in different eukaryotic species. The resulting network of co-evolving and functionally associated modifications reveals the global landscape of post-translational regulation.
In all, 115 149 non-redundant post-translational modifications (PTMs) of 13 different types were collected from 8 eukaryotes.Comparison of evolution speed reveals that carboxylation is the most conserved while SUMOylation is the fastest evolving PTM type.Co-evolution of PTM pairs that co-occur within proteins reveals a vastly interconnected global network of functionally associated PTM types in eukaryotes.Central to the network of functionally associated PTM types appear phosphorylation, acetylation, ubiquitination and O-linked glycosylation that control both temporal events and processes that govern protein localization.
Various post-translational modifications (PTMs) fine-tune the functions of almost all eukaryotic proteins, and co-regulation of different types of PTMs has been shown within and between a number of proteins. Aiming at a more global view of the interplay between PTM types, we collected modifications for 13 frequent PTM types in 8 eukaryotes, compared their speed of evolution and developed a method for measuring PTM co-evolution within proteins based on the co-occurrence of sites across eukaryotes. As many sites are still to be discovered, this is a considerable underestimate, yet, assuming that most co-evolving PTMs are functionally associated, we found that PTM types are vastly interconnected, forming a global network that comprise in human alone >50 000 residues in about 6000 proteins. We predict substantial PTM type interplay in secreted and membrane-associated proteins and in the context of particular protein domains and short-linear motifs. The global network of co-evolving PTM types implies a complex and intertwined post-translational regulation landscape that is likely to regulate multiple functional states of many if not all eukaryotic proteins.
PMCID: PMC3421446  PMID: 22806145
post-translational modifications; protein regulation; proteomics; PTM code; PTM crosstalk
Yilmaz, Pelin | Kottmann, Renzo | Field, Dawn | Knight, Rob | Cole, James R | Amaral-Zettler, Linda | Gilbert, Jack A | Karsch-Mizrachi, Ilene | Johnston, Anjanette | Cochrane, Guy | Vaughan, Robert | Hunter, Christopher | Park, Joonhong | Morrison, Norman | Rocca-Serra, Philippe | Sterk, Peter | Arumugam, Manimozhiyan | Bailey, Mark | Baumgartner, Laura | Birren, Bruce W | Blaser, Martin J | Bonazzi, Vivien | Booth, Tim | Bork, Peer | Bushman, Frederic D | Buttigieg, Pier Luigi | Chain, Patrick S G | Charlson, Emily | Costello, Elizabeth K | Huot-Creasy, Heather | Dawyndt, Peter | DeSantis, Todd | Fierer, Noah | Fuhrman, Jed A | Gallery, Rachel E | Gevers, Dirk | Gibbs, Richard A | Gil, Inigo San | Gonzalez, Antonio | Gordon, Jeffrey I | Guralnick, Robert | Hankeln, Wolfgang | Highlander, Sarah | Hugenholtz, Philip | Jansson, Janet | Kau, Andrew L | Kelley, Scott T | Kennedy, Jerry | Knights, Dan | Koren, Omry | Kuczynski, Justin | Kyrpides, Nikos | Larsen, Robert | Lauber, Christian L | Legg, Teresa | Ley, Ruth E | Lozupone, Catherine A | Ludwig, Wolfgang | Lyons, Donna | Maguire, Eamonn | Methé, Barbara A | Meyer, Folker | Muegge, Brian | Nakielny, Sara | Nelson, Karen E | Nemergut, Diana | Neufeld, Josh D | Newbold, Lindsay K | Oliver, Anna E | Pace, Norman R | Palanisamy, Giriprakash | Peplies, Jörg | Petrosino, Joseph | Proctor, Lita | Pruesse, Elmar | Quast, Christian | Raes, Jeroen | Ratnasingham, Sujeevan | Ravel, Jacques | Relman, David A | Assunta-Sansone, Susanna | Schloss, Patrick D | Schriml, Lynn | Sinha, Rohini | Smith, Michelle I | Sodergren, Erica | Spor, Aymé | Stombaugh, Jesse | Tiedje, James M | Ward, Doyle V | Weinstock, George M | Wendel, Doug | White, Owen | Whiteley, Andrew | Wilke, Andreas | Wortman, Jennifer R | Yatsunenko, Tanya | Glöckner, Frank Oliver
Nature Biotechnology  2011;29(5):415-420.
Here we present a standard developed by the Genomic Standards Consortium (GSC) for reporting marker gene sequences—the minimum information about a marker gene sequence (MIMARKS). We also introduce a system for describing the environment from which a biological sample originates. The ‘environmental packages’ apply to any genome sequence of known origin and can be used in combination with MIMARKS and other GSC checklists. Finally, to establish a unified standard for describing sequence data and to provide a single point of entry for the scientific community to access and learn about GSC checklists, we present the minimum information about any (x) sequence (MIxS). Adoption of MIxS will enhance our ability to analyze natural genetic diversity documented by massive DNA sequencing efforts from myriad ecosystems in our ever-changing biosphere.
PMCID: PMC3367316  PMID: 21552244
9.  Transcription start site associated RNAs in bacteria
A new class of small RNA (~45 bases long) is identified in gram positive and negative bacteria. These tssRNAs are associated with RNA polymerase pausing some 45 bases downstream of the transcription start site and show global changes in expression during the growth cycle.
A new class of bacterial small RNAs have been identified. They are related to eukaryotic tiRNAs in their localization (transcription start sites, TSS) but not in their biogenesis.tssRNAs are generated at the same positions as long transcripts, as well as at independent positions, but both seem to have promoter-like characteristics (Pribnow box).We provide compelling evidence that tssRNAs are not mRNA degradation products and neither abortive transcripts; rather, they are newly synthesized transcripts and require more factors than the basal transcription machinery (i.e., RNA polymerase subunits)tssRNAs show dynamic behavior dependent on the growth phase.We show that RNA polymerase is halted at tssRNAs positions, both in bona fide genes and in positions where no long transcript is produced. This indicates that tssRNAs could be generated by RNA polymerase pausing to ensure that no spurious long RNA is generated by random appearance of Pribnow sequences in the genome.
Here, we report the genome-wide identification of small RNAs associated with transcription start sites (TSSs), termed tssRNAs, in Mycoplasma pneumoniae. tssRNAs were also found to be present in a different bacterial phyla, Escherichia coli. Similar to the recently identified promoter-associated tiny RNAs (tiRNAs) in eukaryotes, tssRNAs are associated with active promoters. Evidence suggests that these tssRNAs are distinct from previously described abortive transcription RNAs. ssRNAs have an average size of 45 bases and map exactly to the beginning of cognate full-length transcripts and to cryptic TSSs. Expression of bacterial tssRNAs requires factors other than the standard RNA polymerase holoenzyme. We have found that the RNA polymerase is halted at tssRNA positions in vivo, which may indicate that a pausing mechanism exists to prevent transcription in the absence of genes. These results suggest that small RNAs associated with TSSs could be a universal feature of bacterial transcription.
PMCID: PMC3377991  PMID: 22617959
non-coding RNAs; small RNAs; transcription; transcriptomics
11.  Prediction and identification of sequences coding for orphan enzymes using genomic and metagenomic neighbours
Many characterized metabolic enzymes currently lack associated gene and protein sequences. Here, pathway and genomic neighbour data are used to assign genes to these ‘orphan enzymes,' and the predictions are validated with experimental assays and genome-scale metabolic modelling.
A computational method is developed for assigning candidate sequences to orphan enzymes. The method uses metabolic pathway, genomic neighbourhood, genomic co-occurrence, and protein domain information to predict genes that are likely to perform a particular enzymatic function.Benchmarking of the scoring scheme based on the 4 features above revealed that some combinations of parameters yielded greater than 70% accuracy, and that high-confidence predictions could be generated for 131 orphan enzymes.Enzyme assay experiments confirmed the predicted enzymatic activity for two of the high-confidence candidate sequences.Predicted functions can improve the annotation of genomic and metagenomic data, and can reveal putative genes for enzymes with potential biotechnological applications.Incorporating the predicted enzymatic reactions into genome-scale metabolic models changed the flux connectivity and improved their ability to correctly predict gene essentiality, supporting the biological relevance of these predictions.
Despite the current wealth of sequencing data, one-third of all biochemically characterized metabolic enzymes lack a corresponding gene or protein sequence, and as such can be considered orphan enzymes. They represent a major gap between our molecular and biochemical knowledge, and consequently are not amenable to modern systemic analyses. As 555 of these orphan enzymes have metabolic pathway neighbours, we developed a global framework that utilizes the pathway and (meta)genomic neighbour information to assign candidate sequences to orphan enzymes. For 131 orphan enzymes (37% of those for which (meta)genomic neighbours are available), we associate sequences to them using scoring parameters with an estimated accuracy of 70%, implying functional annotation of 16 345 gene sequences in numerous (meta)genomes. As a case in point, two of these candidate sequences were experimentally validated to encode the predicted activity. In addition, we augmented the currently available genome-scale metabolic models with these new sequence–function associations and were able to expand the models by on average 8%, with a considerable change in the flux connectivity patterns and improved essentiality prediction.
PMCID: PMC3377989  PMID: 22569339
genomics; metabolic pathways; metagenomics; neighbourhood information; orphan enzymes
12.  Annotation of the M. tuberculosis Hypothetical Orfeome: Adding Functional Information to More than Half of the Uncharacterized Proteins
PLoS ONE  2012;7(4):e34302.
The genome of Mycobacterium tuberculosis (H37Rv) contains 4,019 protein coding genes, of which more than thousand have been categorized as ‘hypothetical’ implying that for these not even weak functional associations could be identified so far. We here predict reliable functional indications for half of this large hypothetical orfeome: 497 genes can be annotated based on orthology, and another 125 can be linked to interacting proteins via integrated genomic context analysis and literature mining. The assignments include newly identified clusters of interacting proteins, hypothetical genes that are associated to well known pathways and putative disease-relevant targets. All together, we have raised the fraction of the proteome with at least some functional annotation to 88% which should considerably enhance the interpretation of large-scale experiments targeting this medically important organism.
PMCID: PMC3317503  PMID: 22485162
13.  Cross-talk between phosphorylation and lysine acetylation in a genome-reduced bacterium
The effect of kinase, phosphatase and N-acetyltransferase deletions on proteome phosphorylation and acetylation was investigated in Mycoplasma pneumoniae. Bi-directional cross-talk between post-transcriptional modifications suggests an underlying regulatory molecular code in prokaryotes.
Post-translational modifications (PTMs) change the chemical properties of proteins, conferring diversity beyond the amino-acid sequence. Proteins are often modified on multiple sites. A PTM code has been proposed, whereby modifications at specific positions influence further modifications. These regulatory circuits though have rarely been studied on a large-scale; conservation in prokaryotes remains elusive.Here, we studied two important PTMs– phosphorylation and lysine acetylation in the small bacterium Mycoplasma pneumoniae. We combined genetics and quantitative mass spectrometry to measure the effect of systematic kinase, phosphatase and N-acetyltransferase deletions on proteome abundance, phosphorylation and lysine acetylation.The data set represents a comprehensive analysis of both phosphorylation and lysine acetylation in a single prokaryote. It reveals (1) proteins often carry multiple modifications and multiple types of PTMs, reminiscent of the PTM code proposed in eukaryotes, (2) phosphorylation exerts pleiotropic effect on proteins abundances, phosphorylation, but also lysine acetylation, (3) the cross-talk between the two PTMs is bi-directional and (4) PTMs are frequently located at interaction interfaces and in multifunctional proteins, illustrating how PTMs could modulate protein functions affecting the way they interact.The study provides an unbiased and quantitative view on cross-talk between phosphorylation and lysine acetylation. It suggests that these regulatory circuits are a fundamental principle of regulation that might have evolved before the divergence of prokaryotes and eukaryotes.
Protein post-translational modifications (PTMs) represent important regulatory states that when combined have been hypothesized to act as molecular codes and to generate a functional diversity beyond genome and transcriptome. We systematically investigate the interplay of protein phosphorylation with other post-transcriptional regulatory mechanisms in the genome-reduced bacterium Mycoplasma pneumoniae. Systematic perturbations by deletion of its only two protein kinases and its unique protein phosphatase identified not only the protein-specific effect on the phosphorylation network, but also a modulation of proteome abundance and lysine acetylation patterns, mostly in the absence of transcriptional changes. Reciprocally, deletion of the two putative N-acetyltransferases affects protein phosphorylation, confirming cross-talk between the two PTMs. The measured M. pneumoniae phosphoproteome and lysine acetylome revealed that both PTMs are very common, that (as in Eukaryotes) they often co-occur within the same protein and that they are frequently observed at interaction interfaces and in multifunctional proteins. The results imply previously unreported hidden layers of post-transcriptional regulation intertwining phosphorylation with lysine acetylation and other mechanisms that define the functional state of a cell.
PMCID: PMC3293634  PMID: 22373819
kinase; N-acetyltransferase; network; phosphatase; post-translational modification
14.  Assessment of Metagenomic Assembly Using Simulated Next Generation Sequencing Data
PLoS ONE  2012;7(2):e31386.
Due to the complexity of the protocols and a limited knowledge of the nature of microbial communities, simulating metagenomic sequences plays an important role in testing the performance of existing tools and data analysis methods with metagenomic data. We developed metagenomic read simulators with platform-specific (Sanger, pyrosequencing, Illumina) base-error models, and simulated metagenomes of differing community complexities. We first evaluated the effect of rigorous quality control on Illumina data. Although quality filtering removed a large proportion of the data, it greatly improved the accuracy and contig lengths of resulting assemblies. We then compared the quality-trimmed Illumina assemblies to those from Sanger and pyrosequencing. For the simple community (10 genomes) all sequencing technologies assembled a similar amount and accurately represented the expected functional composition. For the more complex community (100 genomes) Illumina produced the best assemblies and more correctly resembled the expected functional composition. For the most complex community (400 genomes) there was very little assembly of reads from any sequencing technology. However, due to the longer read length the Sanger reads still represented the overall functional composition reasonably well. We further examined the effect of scaffolding of contigs using paired-end Illumina reads. It dramatically increased contig lengths of the simple community and yielded minor improvements to the more complex communities. Although the increase in contig length was accompanied by increased chimericity, it resulted in more complete genes and a better characterization of the functional repertoire. The metagenomic simulators developed for this research are freely available.
PMCID: PMC3285633  PMID: 22384016
15.  Younger Genes Are Less Likely to Be Essential than Older Genes, and Duplicates Are Less Likely to Be Essential than Singletons of the Same Age
Molecular Biology and Evolution  2012;29(7):1703-1706.
Recently duplicated genes are believed to often overlap in function and expression. A priori, they are thus less likely to be essential. Although this was indeed observed in yeast, mouse singletons and duplicates were reported to be equally often essential. This contradiction can only partly be explained by experimental biases. We herein show that older genes (i.e., genes with earlier phyletic origin) are more likely to be essential, regardless of their duplication status. At a given phyletic gene age, duplicates are always less likely to be essential compared with singletons. The “paradoxical” high essentiality among mouse gene duplicates is then caused by different age profiles of singletons and duplicates, with the latter tending to be derived from older genes.
PMCID: PMC3375470  PMID: 22319151
gene essentiality; yeast; mouse; phyletic age; linking genotype to phenotype
16.  The Tenth Asia Pacific Bioinformatics Conference (APBC 2012)
BMC Genomics  2012;13(Suppl 1):I1.
PMCID: PMC3304854  PMID: 22369290
17.  Prediction of Drug Combinations by Integrating Molecular and Pharmacological Data
PLoS Computational Biology  2011;7(12):e1002323.
Combinatorial therapy is a promising strategy for combating complex disorders due to improved efficacy and reduced side effects. However, screening new drug combinations exhaustively is impractical considering all possible combinations between drugs. Here, we present a novel computational approach to predict drug combinations by integrating molecular and pharmacological data. Specifically, drugs are represented by a set of their properties, such as their targets or indications. By integrating several of these features, we show that feature patterns enriched in approved drug combinations are not only predictive for new drug combinations but also provide insights into mechanisms underlying combinatorial therapy. Further analysis confirmed that among our top ranked predictions of effective combinations, 69% are supported by literature, while the others represent novel potential drug combinations. We believe that our proposed approach can help to limit the search space of drug combinations and provide a new way to effectively utilize existing drugs for new purposes.
Author Summary
The combination of distinct drugs in combinatorial therapy can help to improve therapeutic efficacy by overcoming the redundancy and robustness of pathogenic processes, or by lowering the risk of side effects. However, identification of effective drug combinations is cumbersome, considering the possible search space with respect to the large number of drugs that could potentially be combined. In this work, we explore various molecular and pharmacological features of drugs, and show that by utilizing combinations of such features it is possible to predict new drug combinations. Benchmarking the approach using approved drug combinations demonstrates that these feature combinations are indeed predictive and can propose promising new drug combinations. In addition, the enriched feature patterns provide insights into the mechanisms underlying drug combinations. For example, they suggest that if two drugs share targets or therapeutic effects, they can be independently combined with a third common drug. The ability to efficiently predict drug combinations should facilitate the development of more efficient drug therapies for a broader range of indications including hard-to-treat complex diseases.
PMCID: PMC3248384  PMID: 22219721
18.  Identifying Single Copy Orthologs in Metazoa
PLoS Computational Biology  2011;7(12):e1002269.
The identification of single copy (1-to-1) orthologs in any group of organisms is important for functional classification and phylogenetic studies. The Metazoa are no exception, but only recently has there been a wide-enough distribution of taxa with sufficiently high quality sequenced genomes to gain confidence in the wide-spread single copy status of a gene.
Here, we present a phylogenetic approach for identifying overlooked single copy orthologs from multigene families and apply it to the Metazoa. Using 18 sequenced metazoan genomes of high quality we identified a robust set of 1,126 orthologous groups that have been retained in single copy since the last common ancestor of Metazoa. We found that the use of the phylogenetic procedure increased the number of single copy orthologs found by over a third more than standard taxon-count approaches. The orthologs represented a wide range of functional categories, expression profiles and levels of divergence.
To demonstrate the value of our set of single copy orthologs, we used them to assess the completeness of 24 currently published metazoan genomes and 62 EST datasets. We found that the annotated genes in published genomes vary in coverage from 79% (Ciona intestinalis) to 99.8% (human) with an average of 92%, suggesting a value for the underlying error rate in genome annotation, and a strategy for identifying single copy orthologs in larger datasets. In contrast, the vast majority of EST datasets with no corresponding genome sequence available are largely under-sampled and probably do not accurately represent the actual genomic complement of the organisms from which they are derived.
Author Summary
The correct identification of single copy (1-to-1) orthologs is crucial for functional classification of genes and for phylogenetic studies of groups of organisms, including the Metazoa. Nevertheless, despite the recent increase in the number of genomes and short sequence read datasets (e.g. ESTs) from the Metazoa, we know little about their completeness and how useful they may be for phylogenetic studies. Here we describe a novel approach for the identification of single copy gene families at any hierarchical level and demonstrate its effectiveness by identifying a set of over one thousand gene families that have been in single copy since the last common ancestor of the Metazoa. By comparing our orthologs to those predicted by other datasets we show that our procedure identifies a significantly larger set of single copy orthologs in the Metazoa. We then use this dataset to assess 24 metazoan genomes and 61 metazoan EST datasets for their completeness. We thus identify the underlying error rate in genome annotation and suggest a mechanism for assessing the quality of genomes and EST datasets in terms of their suitability for phylogenetic studies.
PMCID: PMC3228760  PMID: 22144877
19.  InterPro in 2011: new developments in the family and domain prediction database
Nucleic Acids Research  2011;40(D1):D306-D312.
PMCID: PMC3245097  PMID: 22096229
20.  eggNOG v3.0: orthologous groups covering 1133 organisms at 41 different taxonomic ranges
Nucleic Acids Research  2011;40(D1):D284-D289.
Orthologous relationships form the basis of most comparative genomic and metagenomic studies and are essential for proper phylogenetic and functional analyses. The third version of the eggNOG database ( contains non-supervised orthologous groups constructed from 1133 organisms, doubling the number of genes with orthology assignment compared to eggNOG v2. The new release is the result of a number of improvements and expansions: (i) the underlying homology searches are now based on the SIMAP database; (ii) the orthologous groups have been extended to 41 levels of selected taxonomic ranges enabling much more fine-grained orthology assignments; and (iii) the newly designed web page is considerably faster with more functionality. In total, eggNOG v3 contains 721 801 orthologous groups, encompassing a total of 4 396 591 genes. Additionally, we updated 4873 and 4850 original COGs and KOGs, respectively, to include all 1133 organisms. At the universal level, covering all three domains of life, 101 208 orthologous groups are available, while the others are applicable at 40 more limited taxonomic ranges. Each group is amended by multiple sequence alignments and maximum-likelihood trees and broad functional descriptions are provided for 450 904 orthologous groups (62.5%).
PMCID: PMC3245133  PMID: 22096231
21.  OGEE: an online gene essentiality database
Nucleic Acids Research  2011;40(D1):D901-D906.
OGEE is an Online GEne Essentiality database. Its main purpose is to enhance our understanding of the essentiality of genes. This is achieved by collecting not only experimentally tested essential and non-essential genes, but also associated gene features such as expression profiles, duplication status, conservation across species, evolutionary origins and involvement in embryonic development. We focus on large-scale experiments and complement our data with text-mining results. Genes are organized into data sets according to their sources. Genes with variable essentiality status across data sets are tagged as conditionally essential, highlighting the complex interplay between gene functions and environments. Linked tools allow the user to compare gene essentiality among different gene groups, or compare features of essential genes to non-essential genes, and visualize the results. OGEE is freely available at
PMCID: PMC3245054  PMID: 22075992
22.  STITCH 3: zooming in on protein–chemical interactions
Nucleic Acids Research  2011;40(D1):D876-D880.
PMCID: PMC3245073  PMID: 22075997
23.  SMART 7: recent updates to the protein domain annotation resource
Nucleic Acids Research  2011;40(D1):D302-D305.
PMCID: PMC3245027  PMID: 22053084
24.  A Holistic Approach to Marine Eco-Systems Biology
PLoS Biology  2011;9(10):e1001177.
The structure, robustness, and dynamics of ocean plankton ecosystems remain poorly understood due to sampling, analysis, and computational limitations. The Tara Oceans consortium organizes expeditions to help fill this gap at the global level.
PMCID: PMC3196472  PMID: 22028628
25.  Universally Distributed Single-Copy Genes Indicate a Constant Rate of Horizontal Transfer
PLoS ONE  2011;6(8):e22099.
Single copy genes, universally distributed across the three domains of life and encoding mostly ancient parts of the translation machinery, are thought to be only rarely subjected to horizontal gene transfer (HGT). Indeed it has been proposed to have occurred in only a few genes and implies a rare, probably not advantageous event in which an ortholog displaces the original gene and has to function in a foreign context (orthologous gene displacement, OGD). Here, we have utilised an automatic method to identify HGT based on a conservative statistical approach capable of robustly assigning both donors and acceptors. Applied to 40 universally single copy genes we found that as many as 68 HGTs (implying OGDs) have occurred in these genes with a rate of 1.7 per family since the last universal common ancestor (LUCA). We examined a number of factors that have been claimed to be fundamental to HGT in general and tested their validity in the subset of universally distributed single copy genes. We found that differing functional constraints impact rates of OGD and the more evolutionarily distant the donor and acceptor, the less likely an OGD is to occur. Furthermore, species with larger genomes are more likely to be subjected to OGD. Most importantly, regardless of the trends above, the number of OGDs increases linearly with time, indicating a neutral, constant rate. This suggests that levels of HGT above this rate may be indicative of positively selected transfers that may allow niche adaptation or bestow other benefits to the recipient organism.
PMCID: PMC3151239  PMID: 21850220

Results 1-25 (108)


Ch 23 French Rev

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mwitt  on February 18, 2010

Global Patterns of Civilizations II

Georgetown Visitation

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Ch 23 French Rev

First Estate and divisions
clergy: Upper (also part of second estate,bishops, cardinals, abbots) and lower clergy (poorly-paid, parish, priests); privileged, 1% of pop, not taxed

Cards (new!)

Space Race

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Upper clergy views sought to preserve privileges of the Old Regime (conservative) --> favored limited monarchy, agreed and allied with nobility, felt threatened by bourgeoisie, view the peasants as workers and frustrated by their refusal to fulfill feudal obligations
Lower clergy views liberal-minded like the Third Estate, in favor of limited monarchy, resented but respect nobility, ally with bourgeoisie, could identify with peasants
Second Estate and divisions nobility: upper nobility (of the sword sword, old families) and lower nobility (of the robe, social climbers), highest positions in church, army, and bureaucracy from resurgence after death of Louis XIV; 2% of pop who owned 25% of the land, pay no taxes
Upper Nobility views conservative, sought limited monarchy to preserve rights, support clergy, threatened by bourgeioisie frustrated by complaints of peasants; served the king at Versailles, had the name, power, and wealth
Lower nobility views "liberal", sought limited monarchy but depended on the king for their social status, support clergy, threatened by bourgeoisie taking power but they brought more people to their group, frustrated by the complaints of peasants; had the name but not the power
Third estate and divisions everyone else: bourgeoisie, peasantry, and urban workers (sans-culottes), 25 million
Bourgeoisie views frustrated with monarchy because of limited privileges and sought limited monarchy, tension with clergy because they oppose the rcc, envious and resentful of nobility, wealthy but not privilege: merchants, manufacturers, bankers, doctors, lawyers, intellectuals, owned 20% of land
Peasant views rebellious of monarchy because they were always hit with taxes, very loyal to the clergy, great resentment of nobility, 21 million
urban workers resent monarchy, clergy, and nobility
Louis XVI and Marie Antoniette weak leadership were a cause of the French Rev
Parlements 13 regional law courts, the most powerful of which is the one in Paris, used as an arm for nobilty for blocking king's decrees (no unified law)
Causes of French Revolution social, political, intellectual, economc
Social causes of French Rev rigid social hierarchy --> 3 estates and tremendous grievances against the inequality of privileges
Political causes of French Rev struggle between weak leadership of the monarchy and the Resurgent aristocracy
Intellectual causes of French Rev enlightenment ideas: change is good, progress for humanity and american revolution: inspiration, proof that progress is possible and that common man can win (common man vs. tyranny)
Economic causes of French Rev wealth not distributed, huge gaps between rich and poor, debt, poor harvest --> rising bread prices --> tension
Cause of France's debt support of the American Rev and the Seven Years war
National Assembly June 17, 1789: created a new legislative body with the Third Estate and the lower clergy combined
Attempt to allieviate French debt taxes on the nobility and clergy but the parlement claimed that only the Estates General should pay
Estates General Louis XVI's advisory
Tennis Court Oath NA was locked out of their building so took an oath to stay on the tennis court until thy had given France a constitution. Although called to desist by the king, most of the clergy and nobles joined --> June 27 the king gave in and NA became National Constituent Assembly
Storming of the BastilleWho: Parisian crowd and the royal troops
• Parisian crowd marched to the Bastille looking for weapons of the militia
• Royal troops killed 98 in the crowd
• Crowd stormed the fortress and released several prisoners, killed several soldiers, and the governor
• Did not find weapons
When: July 14, 1789
Where: Paris, France; The Bastille (a great fortress that formerly held
political prisoners)
Why: Showed that the political future would not only be controlled by
the NCA
The Great FearWho: French peasants and the French nobility
• The actions of the peasants against the nobles in the French countryside
• The peasants vent about injustices against them, reclaim rights and properties lost in aristocratic resurgence in the last 25 years, and refuse to pay feudal dues
• Burned chateaux, destroyed documents
When: July-August 1789
Where: French countryside
Result of the Great Fear August 4, 1789 decree: members of First and Second Estate surrendered their special privileges so that France's laws applied equality for all
Declaration of the Rights of ManWho: created by NCA
What: says:
• all men were born free and equal with natural rights to liberty, property (sacred), and personal safety
• gov't exists to protect those rights
• all political leadership is in the nation and its representatives and all citizens are eligible for public office
• all citizens equal before law and have right to due process, innocence until proven guilty
• freedom of religion
• heaviness of taxation based on capacity to pay
When: August 27, 1789
Women's March on VersaillesBread shortages continued
Who: several thousand Parisian women
- women march to Versailles demanding bread
When: October 5, 1789
Where: Paris to Versailles
- One of many times that women play an important role in crowd revolt
- October 6, 1789 (the next day), the king and his family follow the women back to Paris. Followed by the NCA
Louis XVI's reaction to the Declaration of the Right of Man he stalled the ratification of the declaration and the ending of feudalism --> made people think he might resort to force
Civil Constitution of the clergy1790: i. made French RCC a branch of secular state
ii. priests and bishops elected to serve w/ state salaries
iii. demanded all clergy take oath to the Constitution, the many who did were
deemed refractory and were removed from the Church
iv. Constitution and the Declaration condemned by the Pope (Feb 1791) and
divided French into those loyal to the Church and those loyal to the
Revolution (including Louis who favored the Revolution)
Declaration of Pillnitza result of Fleeing of Louis XVI (summer 1791)
a. Was caught and forced back -->assembly now saw the king as a counterrevolutionary
b. August 27, 1791 : Kings of Russia and Prussia promise to protect the French royal family
i. the declaration required Britain's agreement and because they refused, it was
ii. Showed French revolutionaries they were surrounded by aristocratic and monarchial foes
Legislative assembly led by the Girondists voted to declare war on Austria (who was allied w/ Prussia) --> Second Revolution to overthrow monarchy and establish republic (in the National Convention)
Constitution of 1791 Established constitutional monarchy (The Legislative Assembly, one house)
ii. Monarch could only delay legislation
iii. only 50,000 men could be elected or serve
Desires of the bourgeoisie in Stage One free-trade economy and limited monarchy
Declaration of the Rights of Women b. Olympe de Gouges' reaction
i. Olympe, from butcher's daughter  radical
ii. composed THIS DOCUMENT (1793)
A. asked for equal rights for women
Political clubs formed in the early stages of the Revolution Jacobins and Girondists
Jacobins the best organized in France, the radical republican party (displaced Girondists), majority in new Legislative assembly
Girondists group of Jacobins
san-culottesurban workers, antimonarchical, republican group of lower middle class and artisans of Paris (urban working class), . ignored by the policies of the Old Regime and left unprotected by the NCA's
policies of free-market economy  suspicious of gov't, advocated small property owners, and resented social inequality  hostile to aristocracy and original revolutionaries
ii. Wanted price controls for food
Role of the King in Stage One to submit to the will of the refractory, was giving away his power
National Conventionled by the moderate bourgeoisie, during the second revolution,the Paris Commune called for Legislative Assembly to elect a new assembly (the Convention) and write a democratic constitution. Convention meet in 1792 and declared France a republic. the Mountain Jacobins (highly seated in the Convention) worked w/ san-culottes to pass revolutionary reforms and win the war Convention took control of French gov't
Second Revolutionled by the san-culottes and Mountain Jacobins
5. January 21, 1793: Louis XVI was beheaded on the charge of conspiring against the state
a. The killing shocked Europe  France was isolated and at war with everyone, including civil war
Committee of Public Safetycreated by the Convention to safeguard the revolution from enemies from both within and outside Franceb. Became an almost dictatorial power and worked with Paris sans-culottes but they later invaded Convention, drove out the Girondists, and gave the Mountains complete control --> impose price controls
levee en masse a. 1793: Convention decree - draft of all males into the army and harnessed the economy
for war production
Republic of virtue dechristianization of France
i. Notre Dame Temple of Reason
ii. A new, rationalized calendar was created, w/ twelve months named after
seasons and climates (starting from the creation of the Republic)
iii. Churches were closed and Christians were persecuted
iv. the general reaction of the citizens was against
Maximillian Robespierrea.
i. Emerged as a chief figure of the Committee of Public Safety in 1794
ii. Jacobins were his power base and was supported by san-culottes
iii. Understood that dechristianization was a politically bad idea
iv. Robespierre created a law that allowed him to convict w/o evidence  thousands of executions
v. Replaced the worship of reason with the Cult of the Supreme Being  coup  his execution  end of the Reign of Terror
Reign of Terror - the period between the summer of 1793 and the end of July 1794 when the French revolutionary state used 40,000 executive executions and violence to defend the Revolution and suppress internal enemies
a. Victims: mostly peasants an san-culottes
Factors causing Reign of Terror a. Fear created by the internal and external wars
b. Revolutionary aspirations of the Convention and san-culottes
Thermodorian Reaction (3rd phase) July 1794: establishment of new constitutional regime, reaction against radicalism of the French rev, excitement begins to settle
Directory executive branch of the Convention made of 5 people created by the thermodorian constitution of the year III
Why did the French Rev become more radical in stage two? because the king was out of the picture and they did not know how to lead without one
what caused the rise of counterrevolutionaries? the counterrevolutionaries, the san-culottes, wanted price controls to protect themselves and received a chance when they were let into the convention
Demands of the sans-culottes and the radical Jacobins in Stage Two price control
Causes of the end of the Reign of Terror the execution of Robespierre
FR Events in 1789 (8) June: Third Estate --> NA and Oath on the Tennis Court, July: Storming of the Bastille, the Great Fear (through August), August: National Assembly abolished feuday privileges, NA issues Declaration, October: Women march on versailles and force the roysl family to return to paris
FR Events of 1790 (2) Civil Constitution of Clergy and Louis agrees to constitutional monarchy
FR Events of 1791 (2) June: Arrest of the royal family as they attempt to flee, August: Declaration of Pillnitz
FR Events of 1792 (3) April: France declares war on Austria, August: take Louis prisoner, NC declares France a republic and abolished monarchy
FR Events of 1793 (5) January: execution of Louis, March: struggle in NC between Girondists and the Mountain, April-June: creation of Committee of Public Safety, Sept: Price controls
FR Events of 1793-94 (3) Reign of Terror, spring (4): french armies victorious on all fronts, July (4): execution of robespierre --> thermodorian reaction

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