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The enzymes can be loaded into a nasal spray that wipes out pathogens such as Pneumococcus , Staphylococcus , and group A Strep on contact with mucous membranes. The strategy might prevent bacterial infections from spreading in close quarters like hospitals, nursing homes, and daycare centers. Fischetti says, “Clinical... | 14966545_p21 | 14966545 | Phage Therapy | 2.137116 | biomedical | Other | [
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Fischetti and his colleagues have moved on to using the enzymes systemically to wipe out Bacillus anthracis spores, preventing them from germinating and seething through the bloodstream, producing deadly toxins. An IV drip would be started after exposure to the spores. The method, Fischetti reports, is already successf... | 14966545_p22 | 14966545 | Phage Therapy | 3.47119 | biomedical | Other | [
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Up to now the enzymes must make contact with bacteria to kill, but Fischetti is hoping that a new generation of engineered enzymes will be able to kill pathogens inside cells too. A second disadvantage is that they are effective only against gram-positive bacteria, although that group includes many vicious pathogens. | 14966545_p23 | 14966545 | Phage Therapy | 2.287433 | biomedical | Other | [
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But phage enzymes seem to offer one very big advantage: resistance to them has yet to develop. Fischetti says, “We've tried very hard to identify resistant bacteria, but so far we haven't found resistant organisms in all three of the enzymes we're working with. It appears to be a very rare event, much rarer than resist... | 14966545_p24 | 14966545 | Phage Therapy | 2.493047 | biomedical | Other | [
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There is no shortage of ideas for unearthing new antibiotic candidates. Why are they so slow to enter medical practice? The bottleneck, researchers agree, lies in the development process of turning them into effective therapies. Several researchers blame the big pharmaceutical companies that got so big by leading the w... | 14966545_p25 | 14966545 | Antibiotics in the 21st Century | 1.62736 | biomedical | Other | [
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Half a billion at least, says Francis Tally, a big pharmaceuticals veteran who is now chief scientific officer at Cubist Pharmaceuticals, a biotech company located in Lexington, Massachusetts. According to Tally, Cubist produced daptomycin, approved in September 2003, by licensing it from Eli Lilly, which shelved the n... | 14966545_p26 | 14966545 | Antibiotics in the 21st Century | 1.224172 | other | Other | [
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But, Tally argues, the size of the market is not the only barrier to new antibiotics. Combinatorial chemistry and the genomics revolution have simply not delivered on their early promise. “The pipeline is very dry,” he says. “There's been a real lag at the basic research level.” | 14966545_p27 | 14966545 | Antibiotics in the 21st Century | 1.613155 | biomedical | Other | [
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“Antibiotic discovery is hard,” Shapiro says. “It's a huge long process to get a decent antibiotic.” Walsh agrees. “It's easier to find inhibitors of particular enzymes for particular processes—and a very long road to convert that into something for development.” | 14966545_p28 | 14966545 | Antibiotics in the 21st Century | 1.749457 | biomedical | Other | [
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In the meantime, there is a rising clamor to slow down the rate at which bacteria develop resistance. Doctors are exhorted to cut back on prescribing antibiotics and decline to prescribe for viral diseases, which antibiotics can't combat, even when their patients badger them. | 14966545_p29 | 14966545 | Antibiotics in the 21st Century | 1.584742 | biomedical | Other | [
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But even if antibiotic consumption slowed, we will still need new antibiotics. “I always say it's not a matter of if, it's only a matter of when,” says Walsh. “There will always be a need for new antibiotics because the clock starts ticking on the useful lifetime of any antibiotic once you start to use it. That cannot ... | 14966545_p30 | 14966545 | Antibiotics in the 21st Century | 1.437713 | biomedical | Other | [
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Wolbachia are intracellular gram-negative bacteria that are found in association with a variety of invertebrate species, including insects, mites, spiders, terrestrial crustaceans, and nematodes. Wolbachia are transovarialy transmitted from females to their offspring and are extremely widespread, having been found to i... | 15024419_p0 | 15024419 | Introduction | 4.286119 | biomedical | Study | [
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Wolbachia– host interactions are complex and range from mutualistic to pathogenic, depending on the combination of host and Wolbachia involved. Most striking are the various forms of “reproductive parasitism” that serve to alter host reproduction in order to enhance the transmission of this maternally inherited agent. ... | 15024419_p1 | 15024419 | Introduction | 4.16263 | biomedical | Study | [
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Wolbachia have been hypothesized to play a role in host speciation through the reproductive isolation they generate in infected hosts . They also provide an intriguing array of evolutionary solutions to the genetic conflict that arises from their uniparental inheritance. These solutions represent alternatives to classi... | 15024419_p2 | 15024419 | Introduction | 4.245572 | biomedical | Review | [
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Despite their common occurrence and major effects on host biology, little is currently known about the molecular mechanisms that mediate the interactions between Wolbachia and their invertebrate hosts. This is partly due to the difficulty of working with an obligate intracellular organism that is difficult to culture a... | 15024419_p3 | 15024419 | Introduction | 4.092011 | biomedical | Study | [
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The w Mel genome is determined to be a single circular molecule of 1,267,782 bp with a G+C content of 35.2%. This assembly is very similar to the genetic and physical map of the closely related strain w MelPop . The genome does not exhibit the GC skew pattern typical of some prokaryotic genomes that have two major shif... | 15024419_p4 | 15024419 | Genome Properties | 4.281169 | biomedical | Study | [
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The most striking feature of the w Mel genome is the presence of very large amounts of repetitive DNA and DNA corresponding to mobile genetic elements, which is unique for an intracellular species. In total, 714 repeats of greater than 50 bp in length, which can be divided into 158 distinct families ( Table S1 ), were ... | 15024419_p5 | 15024419 | Repetitive and Mobile DNA | 4.493504 | biomedical | Study | [
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Three prophage elements are present in the genome. One is a small pyocin-like element made up of nine genes . The other two are closely related to and exhibit extensive gene order conservation with the WO phage described from Wolbachia sp. w Kue . Thus, we have named them w Mel WO-A and WO-B, based upon their location ... | 15024419_p6 | 15024419 | Repetitive and Mobile DNA | 4.324405 | biomedical | Study | [
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] | en | 0.999995 |
The irregular pattern of GC skew in w Mel is likely due in part to intragenomic rearrangements associated with the many DNA repeat elements. Comparison with a large contig from a Wolbachia species that infects Brugia malayi is consistent with this . While only translocations are seen in this plot, genetic comparisons r... | 15024419_p7 | 15024419 | Genome Structure: Rearrangements, Duplications, and Deletions | 4.510075 | biomedical | Study | [
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Although the common ancestor of Wolbachia and Rickettsia likely already had a reduced, streamlined genome, w Mel has lost additional genes since that time ( Table S3 ). Many of these recent losses are of genes involved in cell envelope biogenesis in other species, including most of the machinery for producing lipopolys... | 15024419_p8 | 15024419 | Genome Structure: Rearrangements, Duplications, and Deletions | 4.465195 | biomedical | Study | [
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] | en | 0.999998 |
Despite evident genome reduction in w Mel and in contrast to most small-genomed intracellular species, gene duplication appears to have continued, as over 50 gene families have apparently expanded in the w Mel lineage relative to that of all other species ( Table S4 ). Many of the pairs of duplicated genes are encoded ... | 15024419_p9 | 15024419 | Genome Structure: Rearrangements, Duplications, and Deletions | 4.289579 | biomedical | Study | [
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One duplication of particular interest is that of wsp , which is a standard gene for strain identification and phylogenetic reconstruction in Wolbachia . In addition to the previously described wsp , w Mel encodes two wsp paralogs , which we designate as wspB and wspC , respectively. While these paralogs are highly div... | 15024419_p10 | 15024419 | Genome Structure: Rearrangements, Duplications, and Deletions | 4.278307 | biomedical | Study | [
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The fraction of the genome that is repetitive DNA and the fraction that corresponds to mobile genetic elements are among the highest for any prokaryotic genome. This is particularly striking compared to the genomes of other obligate intracellular species such as Buchnera , Rickettsia , Chlamydia , and Wigglesworthia , ... | 15024419_p11 | 15024419 | Inefficiency of Selection in w Mel | 4.272795 | biomedical | Study | [
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We propose that the mobile DNA in w Mel was acquired some time after the separation of the Wolbachia and Rickettsia lineages but before the radiation of the Wolbachia group . The acquisition of these elements after the separation of the Wolbachia and Rickettsia lineages is suggested by the fact that most do not have an... | 15024419_p12 | 15024419 | Inefficiency of Selection in w Mel | 4.557877 | biomedical | Study | [
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] | [
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] | en | 0.999997 |
It is likely that much of the mobile/repetitive DNA was introduced via phage, given that three prophage elements are present; experimental studies have shown active phage in some Wolbachia and Wolbachia superinfections occur in many hosts , which would allow phage to move between strains. Whatever the mechanism of intr... | 15024419_p13 | 15024419 | Inefficiency of Selection in w Mel | 4.539308 | biomedical | Study | [
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Low rates of recombination, such as occur in centromeres and the human Y chromosome, can lead to inefficient selection because of the linkage among genes. This has been suggested to be occurring in Buchnera species because these species do not encode homologs of RecA, which is the key protein in homologous recombinatio... | 15024419_p14 | 15024419 | Inefficiency of Selection in w Mel | 4.267865 | biomedical | Study | [
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] | en | 0.999997 |
Another possible explanation for inefficient selection is high mutation rates. It has been suggested that the higher evolutionary rates in intracellular bacteria are the result of high mutation rates that are in turn due to the loss of genes for DNA repair processes . This is likely not the case in w Mel since its geno... | 15024419_p15 | 15024419 | Inefficiency of Selection in w Mel | 4.537375 | biomedical | Study | [
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We believe that the most likely explanations for the inefficiency of selection in w Mel involve population-size related factors, such as genetic drift and the occurrence of population bottlenecks. Such factors have also been shown to likely explain the high evolutionary rates in other intracellular species . Wolbachia ... | 15024419_p16 | 15024419 | Inefficiency of Selection in w Mel | 4.298988 | biomedical | Study | [
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] | [
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0.000557948078494519,
0.0005877637304365635,
0.00008212251850636676
] | en | 0.999998 |
There is a general consensus in the evolutionary biology literature that the mitochondria evolved from bacteria in the α-subgroup of the Proteobacteria phyla . Analysis of complete mitochondrial and bacterial genomes has very strongly supported this hypothesis . However, the exact position of the mitochondria within th... | 15024419_p17 | 15024419 | Mitochondrial Evolution | 4.192296 | biomedical | Study | [
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In our analysis of complete genomes, including that of w Mel, the first non- Rickettsia member of the Rickettsiales order to have its genome completed, we find support for a grouping of Wolbachia and Rickettsia to the exclusion of the mitochondria, but not for placing the mitochondria within the Rickettsiales order . S... | 15024419_p18 | 15024419 | Mitochondrial Evolution | 4.263779 | biomedical | Study | [
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0.0001665742020122707,
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This analysis of mitochondrial and α-Proteobacterial genes reinforces the view that ancient protein phylogenies are inherently prone to error, most likely because current models of phylogenetic inference do not accurately reflect the true evolutionary processes underlying the differences observed in contemporary amino ... | 15024419_p19 | 15024419 | Mitochondrial Evolution | 4.195308 | biomedical | Study | [
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Many genes that were once encoded in mitochondrial genomes have been transferred into the host nuclear genomes. Searching for such genes has been complicated by the fact that many of the transfer events happened early in eukaryotic evolution and that there are frequently extreme amino acid and nucleotide composition bi... | 15024419_p20 | 15024419 | Host–Symbiont Gene Transfers | 4.286983 | biomedical | Study | [
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While organelle to nuclear gene transfers are generally accepted, there is a great deal of controversy over whether other gene transfers have occurred from bacteria into animals. In particular, claims of transfer from bacteria into the human genome were later shown to be false . Wolbachia are excellent candidates for s... | 15024419_p21 | 15024419 | Host–Symbiont Gene Transfers | 4.266972 | biomedical | Study | [
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w Mel is predicted to have very limited capabilities for membrane transport, for substrate utilization, and for the biosynthesis of metabolic intermediates , similar to what has been seen in other intracellular symbionts and pathogens . Almost all of the identifiable uptake systems for organic nutrients in w Mel are fo... | 15024419_p22 | 15024419 | Metabolism and Transport | 4.616837 | biomedical | Study | [
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0.0007507753907702863,
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Many of the predicted metabolic properties of w Mel, such as the focus on amino acid transport and the presence of limited carbohydrate metabolism, are similar to those found in Rickettsia. A major difference with the Rickettsia spp. is the absence of the ADP–ATP exchanger protein in w Mel. In Rickettsia this protein i... | 15024419_p23 | 15024419 | Metabolism and Transport | 4.452089 | biomedical | Study | [
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0.0005109924823045731,
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The w Mel genome is predicted to encode few proteins for regulatory responses. Three genes encoding two-component system subunits are present: two sensor histidine kinases and one response regulator . Only six strong candidates for transcription regulators were identified: a homolog of arginine repressors , two members... | 15024419_p24 | 15024419 | Regulatory Responses | 4.322395 | biomedical | Study | [
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0.0004460607306100428,
0.00007228161848615855
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The mechanisms by which Wolbachia infect host cells and by which they cause the diverse phenotypic effects on host reproduction and fitness are poorly understood, and the w Mel genome helps identify potential contributing factors. A complete Type IV secretion system, portions of which have been reported in earlier stud... | 15024419_p25 | 15024419 | Host–Symbiont Interactions | 4.510443 | biomedical | Study | [
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In addition to the two major vir clusters, a paralog of virB8 is also present in the w Mel genome. WD0818 is quite divergent from virB8 and, as such, does not appear to have resulted from a recent gene duplication event. RT-PCR experiments have failed to show expression of this CDS in w Mel-infected Drosophila (data no... | 15024419_p26 | 15024419 | Host–Symbiont Interactions | 4.367495 | biomedical | Study | [
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Genes involved in pathogenicity in bacteria have been found to be frequently associated with regions of anomalous nucleotide composition, possibly owing to transfer from other species or insertion into the genome from plasmids or phage. In the four such regions in w Mel (see above; see Table 3 ), some additional candid... | 15024419_p27 | 15024419 | Host–Symbiont Interactions | 4.41354 | biomedical | Study | [
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Of particular interest for host-interaction functions are the large number of genes that encode proteins that contain ankyrin repeats ( Table 4 ). Ankyrin repeats, a tandem motif of around 33 amino acids, are found mainly in eukaryotic proteins, where they are known to mediate protein–protein interactions . While they ... | 15024419_p28 | 15024419 | Host–Symbiont Interactions | 4.461173 | biomedical | Study | [
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Analysis of the w Mel genome reveals that it is unique among sequenced genomes of intracellular organisms in that it is both streamlined and massively infected with mobile genetic elements. The persistence of these elements in the genome for apparently long periods of time suggests that w Mel is inefficient at getting ... | 15024419_p29 | 15024419 | Conclusions | 4.339721 | biomedical | Study | [
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w Mel DNA was obtained from D. melanogaster yw 67c23 flies that naturally carry the w Mel infection. w Mel was purified from young adult flies on pulsed-field gels as described previously . Plugs were digested with the restriction enzyme AscI (GG^CGCGCC), which cuts the bacterial chromosome twice , aiding in the entry ... | 15024419_p30 | 15024419 | Purification/source of DNA | 4.27898 | biomedical | Study | [
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0.00011318217002553865
] | en | 0.999997 |
The complete genome sequence was determined using the whole-genome shotgun method . For the random shotgun-sequencing phase, libraries of average size 1.5–2.0 kb and 4.0–8.0 kb were used. After assembly using the TIGR Assembler , there were 78 contigs greater than 5000 bp, 186 contigs greater than 3000 bp, and 373 cont... | 15024419_p31 | 15024419 | Library construction/sequencing/closure | 4.291992 | biomedical | Study | [
0.9993277788162231,
0.0004085061955265701,
0.0002637199650052935
] | [
0.9993413090705872,
0.0002887809241656214,
0.0002737128525041044,
0.00009609691187506542
] | en | 0.999996 |
Since it has been suggested that Wolbachia and their hosts may undergo lateral gene transfer events , genome assemblies were rerun using all of the shotgun and closure reads without excluding any sequences that appeared to be of host origin. Only five assemblies were found to match both the D. melanogaster genome and t... | 15024419_p32 | 15024419 | Library construction/sequencing/closure | 4.145427 | biomedical | Study | [
0.9994612336158752,
0.00026639565476216376,
0.000272326054982841
] | [
0.9989259839057922,
0.0007507876725867391,
0.00021683880186174065,
0.00010639049287419766
] | en | 0.999998 |
Repeats were identified using RepeatFinder , which makes use of the REPuter algorithm to find maximal-length repeats. Some manual curation and BLASTN and BLASTX searches were used to divide repeat families into different classes. | 15024419_p33 | 15024419 | Repeats | 3.295487 | biomedical | Study | [
0.9981491565704346,
0.0002953750954475254,
0.0015555224381387234
] | [
0.8736299872398376,
0.12434703856706619,
0.0013752506347373128,
0.0006477290880866349
] | en | 0.999996 |
Identification of putative protein-encoding genes and annotation of the genome was done as described previously . An initial set of ORFs likely to encode proteins (CDS) was identified with GLIMMER . Putative proteins encoded by the CDS were examined to identify frameshifts or premature stop codons compared to other spe... | 15024419_p34 | 15024419 | Annotation | 4.196932 | biomedical | Study | [
0.9994621872901917,
0.00031723122810944915,
0.00022049661492928863
] | [
0.99921715259552,
0.0003374837979208678,
0.0003653135499916971,
0.00008006286225281656
] | en | 0.999997 |
All putative w Mel proteins were searched using BLASTP against the predicted proteomes of published complete organismal genomes and a set of complete plastid, mitochondrial, plasmid, and viral genomes. The results of these searches were used (i) to analyze the phylogenetic profile , (ii) to identify putative lineage-sp... | 15024419_p35 | 15024419 | Comparative genomics | 4.204727 | biomedical | Study | [
0.9994034767150879,
0.00035854955785907805,
0.00023794424487277865
] | [
0.9993473887443542,
0.00020882881653960794,
0.0003577193128876388,
0.00008603958849562332
] | en | 0.999996 |
For phylogenetic analysis, the set of all 38 proteins encoded in both the Marchantia polymorpha and Reclinomonas americana mitochondrial genomes were collected. Acanthamoeba castellanii was excluded due to high divergence and extremely long evolutionary branches. Six genes were excluded from further analysis because th... | 15024419_p36 | 15024419 | Phylogenetic analysis of mitochondrial proteins | 4.380245 | biomedical | Study | [
0.9992827773094177,
0.0004075519973412156,
0.0003096739237662405
] | [
0.9991827607154846,
0.00024591886904090643,
0.0004731059889309108,
0.00009820738341659307
] | en | 0.999998 |
For analyses of individual genes, the 63 proteins encoded in the Reclinomonas mitochondrial genome were compared with FASTA to the proteins from 49 sequenced eubacterial genomes, which included the α-Proteobacteria shown in Figure 5 , R. conorii , and Magnetococcus MC1, one of the more divergent α-Proteobacteria. Of th... | 15024419_p37 | 15024419 | Phylogenetic analysis of mitochondrial proteins | 4.111969 | biomedical | Study | [
0.9994385838508606,
0.0002531270729377866,
0.00030824943678453565
] | [
0.999525785446167,
0.00021152755653019994,
0.00020959558605682105,
0.00005313090514391661
] | en | 0.999997 |
To compare wspB sequences from different Wolbachia strains, PCR was done on total DNA extracted from the following sources: w Ri was obtained from infected adult D. simulans , Riverside strain; w AlbB was obtained from the infected Aa23 cell line , and D. immitis Wolbachia was extracted from adult worm tissue. DNA extr... | 15024419_p38 | 15024419 | Analysis of wspB sequences | 4.127318 | biomedical | Study | [
0.9995143413543701,
0.00024871420464478433,
0.0002369689755141735
] | [
0.9995152950286865,
0.00017518983804620802,
0.00025228658341802657,
0.00005732616045861505
] | en | 0.999997 |
To determine whether the vir -like CDSs, as well as adjacent ORFs, were actively expressed within w Mel as two polycistronic operons, RT-PCR was used. Total RNA was isolated from infected D. melanogaster yw 67c23 adults using Trizol reagent (Invitrogen, Carlsbad, California, United States) and cDNA synthesized using Su... | 15024419_p39 | 15024419 | Type IV secretion system | 4.25507 | biomedical | Study | [
0.9993777275085449,
0.0003503205953165889,
0.0002718681644182652
] | [
0.9993599057197571,
0.0003052329702768475,
0.0002547305775806308,
0.0000801053101895377
] | en | 0.999995 |
The complete sequence for w Mel has been given GenBank ( http://www.ncbi.nlm.nih.gov/Genbank/ ) accession ID number AE017196 and is available through the TIGR Comprehensive Microbial Resourceat http://www.tigr.org/tigr-scripts/CMR2/GenomePage3.spl?database=dmg | 15024419_p40 | 15024419 | Accession Numbers | 1.716569 | biomedical | Other | [
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0.002904098480939865,
0.01184039656072855
] | [
0.013989302329719067,
0.9842867851257324,
0.00042743131052702665,
0.0012964135967195034
] | en | 0.999997 |
The GenBank accession numbers for other sequences discussed in this paper are AF020059 ( Wolbachia sp. w AlbB outer surface protein precursor wsp gene), AF020070 ( Wolbachia sp. w Ri outer surface protein precursor wsp gene), AJ252062 ( Wolbachia endosymbiont of D. immitis sp. gene for surface protein), AJ580921 ( Wolb... | 15024419_p41 | 15024419 | Accession Numbers | 2.952609 | biomedical | Other | [
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0.0005536804092116654,
0.0021868101321160793
] | [
0.15327952802181244,
0.8443957567214966,
0.0008500944240950048,
0.00147471041418612
] | en | 0.999996 |
The number and type of genetic changes that control morphological and physiological changes during vertebrate evolution are not yet known. The evolutionary history of threespine sticklebacks (Gasterosteus aculeatus) provides an unusual opportunity to directly study the genetic architecture of adaptive divergence in nat... | 15069472_p0 | 15069472 | Introduction | 4.225135 | biomedical | Study | [
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0.00019526395772118121,
0.0004660318372771144
] | [
0.9977516531944275,
0.0004711990768555552,
0.0017070828471332788,
0.00007005171937635168
] | en | 0.999996 |
Three distinctive patterns of body armor, now known as the “lateral plate morphs,” have been recognized as one of the most distinguishing characteristics in sticklebacks since at least the early 1800s . Most marine sticklebacks have a continuous row of bony plates that covers the lateral side of the body from head to t... | 15069472_p1 | 15069472 | Introduction | 4.300195 | biomedical | Study | [
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] | [
0.9879902005195618,
0.0012110935058444738,
0.010660670697689056,
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] | en | 0.999996 |
This dramatic variation in lateral plate patterning has led to repeated efforts to determine the genetic basis of the major plate morphs. Previous studies have shown that plate morphs are reproducibly inherited in the laboratory and that crosses between different morphs generate relatively simple ratios of the three ma... | 15069472_p2 | 15069472 | Introduction | 4.370673 | biomedical | Study | [
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0.001210263348184526
] | [
0.9991378784179688,
0.0002016116923186928,
0.0005908936727792025,
0.00006956173456273973
] | en | 0.999999 |
To directly analyze the number and location of genetic loci that control plate phenotypes, we crossed a completely plated marine fish with a low-plated benthic fish from Paxton Lake, British Columbia. Three hundred sixty progeny from a single F2 family (Cross 1) were examined in detail for the pattern, number, and size... | 15069472_p3 | 15069472 | Results | 4.144583 | biomedical | Study | [
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] | [
0.9995840191841125,
0.0001830852561397478,
0.00018652438302524388,
0.00004639072358259
] | en | 0.999996 |
When plate morph was scored as a qualitative trait, a highly significant QTL on linkage group (LG) 4 was detected . The genotype of the QTL on LG 4 was highly predictive of the major plate morph that developed in a fish. Almost all fish that carried two alleles from the complete morph grandparent in the LG 4 region (he... | 15069472_p4 | 15069472 | Results | 4.085275 | biomedical | Study | [
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] | [
0.9993732571601868,
0.0004501944640651345,
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0.0000385587482014671
] | en | 0.999997 |
When total plate number was scored, the same major LG 4 chromosome region accounted for more than 75% of the total variance in plate number of F2 fish. Three additional QTL were detected that had significant effects on plate number in Aa animals . Increasing the number of benthic alleles at any of the individual modifi... | 15069472_p5 | 15069472 | Results | 4.200022 | biomedical | Study | [
0.999125063419342,
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] | [
0.9995465874671936,
0.00022276675736065954,
0.00018393750360701233,
0.00004663526124204509
] | en | 0.999998 |
The size of individual lateral plates varies significantly between different stickleback populations . Although this trait has not been systematically analyzed in previous stickleback crosses, studies of meristic characters in other vertebrates suggest that the size and number of repeating skeletal elements can be cont... | 15069472_p6 | 15069472 | Results | 4.196465 | biomedical | Study | [
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] | [
0.9995480179786682,
0.00018666287360247225,
0.00021953292889520526,
0.000045795422920491546
] | en | 0.999996 |
Some of the differences in previously published models of stickleback plate genetics could be due to different genetic mechanisms operating in different populations. To compare the genetic architecture of armor plate patterning in a separate population located over 1300 km from Paxton Lake, we crossed fish from an unus... | 15069472_p7 | 15069472 | Results | 4.25595 | biomedical | Study | [
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0.9995113611221313,
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0.00025412245304323733,
0.00005447235525934957
] | en | 0.999999 |
To further test whether the same major locus on LG 4 controls armor plate reduction in both populations, we carried out genetic complementation crosses between two low female fish from Friant and one low male fish from Paxton Lake. All 84 progeny developed as low morphs, suggesting that the low-plated phenotype in both... | 15069472_p8 | 15069472 | Results | 4.014111 | biomedical | Study | [
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0.9992823004722595,
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] | en | 0.999996 |
This study reports the first genomewide linkage mapping of lateral plate phenotypes in crosses between major stickleback plate morphs. Our results confirm previous suggestions that dramatic changes in lateral plate patterning can be controlled by one locus of major effect . This major locus on LG 4 can cause a greater ... | 15069472_p9 | 15069472 | QTL Architecture | 4.213182 | biomedical | Study | [
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0.00035886786645278335,
0.0011112174252048135
] | [
0.9995174407958984,
0.00021378765814006329,
0.00021919629944022745,
0.00004957137207384221
] | en | 0.999998 |
Plate number within the complete, partial, and low morphs also varies between fish from different locations. Previous studies suggest that sticklebacks with small changes in plate number show differential survival when exposed to predators, suggesting that selection may fine tune the exact number of plates in different... | 15069472_p10 | 15069472 | QTL Architecture | 4.202206 | biomedical | Study | [
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] | [
0.9993698000907898,
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0.0003952874103561044,
0.000051357554184505716
] | en | 0.999995 |
Postglacial freshwater stickleback populations are thought to be derived from completely plated marine ancestors . At all of the plate QTL detected in Cross 1, the net effect of the freshwater alleles from the Paxton benthic grandparent is to cause a progressive reduction in the size or number of armor plates ( Table 1... | 15069472_p11 | 15069472 | QTL Architecture | 4.196543 | biomedical | Study | [
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] | [
0.9994832277297974,
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0.00018591068510431796,
0.00004574972263071686
] | en | 0.999999 |
Our mapping and complementation results suggest that the same major locus on LG 4 causes major changes in plate pattern in both the Paxton benthic and Friant populations. Phenotypic reduction of lateral plates almost certainly evolved separately in these different locations, given the geographic distance between them ,... | 15069472_p12 | 15069472 | Parallel Evolution | 4.203407 | biomedical | Study | [
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] | [
0.9994274377822876,
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0.00005231460454524495
] | en | 0.999998 |
The present study provides the first genetic mapping evidence that some of the chromosome regions controlling smaller quantitative variation in plate number may also be used repeatedly in different populations. The QTL on LG 26 in Cross 1 maps to a similar position as a QTL influencing plate number within low morph fis... | 15069472_p13 | 15069472 | Parallel Evolution | 4.144471 | biomedical | Study | [
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0.9995456337928772,
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0.00005252156552160159
] | en | 0.999998 |
Recent studies suggest that the same genes are also used repeatedly when pigmentation and larval cuticle phenotypes have evolved in parallel in different fly populations or when melanism has evolved independently in birds and mammals . Repeated use of particular genes may thus be a common theme in parallel evolution of... | 15069472_p14 | 15069472 | Parallel Evolution | 3.917622 | biomedical | Study | [
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0.9438629150390625,
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] | en | 0.999996 |
Why might some genes be used preferentially when similar phenotypes evolve in parallel in wild populations? Alleles that cause plate reduction may already be present at low frequency in marine populations. In that case, parallel phenotypic evolution could occur by repeated selection for the same preexisting alleles in ... | 15069472_p15 | 15069472 | Parallel Evolution | 4.238314 | biomedical | Study | [
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0.9549733400344849,
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A major goal for future work will be to identify the actual genes and mutations that cause parallel evolution of adaptive traits in wild sticklebacks. This study identifies specific markers that are closely linked to chromosome regions that control the pattern, number, and size of lateral plates. With the recent develo... | 15069472_p16 | 15069472 | Parallel Evolution | 4.180039 | biomedical | Study | [
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0.999226450920105,
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] | en | 0.999997 |
For Cross 1, a wild-caught, completely plated marine female from Onnechikappu stream on the east coast of Hokkaido Island, Japan, was crossed to a wild-caught, low-plated benthic male from Paxton Lake, British Columbia. Both parents showed morphologies typical of the marine and benthic populations at their respective c... | 15069472_p17 | 15069472 | Fish crosses and husbandry | 4.189758 | biomedical | Study | [
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] | [
0.9995599389076233,
0.0002555873361416161,
0.0001419945911038667,
0.000042376370402053
] | en | 0.999997 |
Genotyping of microsatellite markers was performed and analyzed essentially as described in Peichel et al. . Some PCR products were analyzed on a 48-capillary array on an ABI3730xl with GeneMapper v3.0 software and GeneScan 500 LIZ (Applied Biosystems, Foster City, California, United States) used as an internal size st... | 15069472_p18 | 15069472 | Genotyping | 4.158587 | biomedical | Study | [
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] | [
0.9993851184844971,
0.0003292507608421147,
0.00022211394389159977,
0.00006352023046929389
] | en | 0.999997 |
Fish were stained with alizarin red to detect skeletal structures as described in Peichel et al. . Lateral plates were counted on both sides of each fish. For QTL mapping, the total plate number of both sides was used. Plate width was measured on the first lateral plate located under the first dorsal spine and above th... | 15069472_p19 | 15069472 | Morphological analysis and QTL mapping | 4.217577 | biomedical | Study | [
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] | [
0.9994445443153381,
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0.00005973227962385863
] | en | 0.999996 |
All morphological traits in Cross 1 were analyzed with MapQTL 4.0 using the same parameters as described by Peichel et al. . Microsatellite markers that were closely linked to QTL detected in Cross 1 were genotyped in all Cross 2 animals . LOD scores between LG 4 markers and the major plate locus in Cross 2 were calcul... | 15069472_p20 | 15069472 | Morphological analysis and QTL mapping | 4.071686 | biomedical | Study | [
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0.999488115310669,
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] | en | 0.999996 |
The GenBank accession numbers for the Bmp6 gene is AY547294 and for the 12 additional new microsatellites Stn 210–219, 222–223 are BV102488–BV102499. | 15069472_p21 | 15069472 | Supporting Information | 2.3039 | biomedical | Other | [
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0.13067013025283813,
0.8664153814315796,
0.00101585837546736,
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] | en | 0.999998 |
By charging authors a fee to have their work published in lieu of charging readers to access articles, open-access publishers such as the Public Library of Science (PLoS) and BioMed Central (BMC) have transformed the traditional publishing system. This reliance on a seemingly untested revenue stream has generated skept... | 15094807_p0 | 15094807 | Publication Charges—Nothing New | 1.09165 | other | Other | [
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] | en | 0.999997 |
Publication fees are not a phenomenon born of the open-access movement. Many authors regularly pay several thousands of dollars in page charges, color charges, correction costs, reprint costs, and other fees to their publisher, even when such costs are entirely voluntary. In the EMBO Journal , for example, authors are ... | 15094807_p1 | 15094807 | Publication Charges—Nothing New | 1.06236 | other | Other | [
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Furthermore, in addition to paying other publication charges, authors may be willing to pay extra for their articles to be made open access, as several publishers have recently recognized. A recent survey of authors in the Proceedings of National Academy of Science ( PNAS ) found that although PNAS already makes its co... | 15094807_p2 | 15094807 | Publication Charges—Nothing New | 1.12845 | other | Other | [
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Although we recognize that authors who submit to PLoS Biology may well be a self-selected group of enthusiastic open-access supporters, we have found that nearly 90% of those who submit manuscripts do not request a fee waiver, and the few who do still offer to pay some portion of the fee. | 15094807_p3 | 15094807 | Publication Charges—Nothing New | 1.060125 | other | Other | [
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] | en | 0.999998 |
The concern about authors' ability to pay publication charges will become less pressing as governments, funding organizations, and institutions increasingly support open-access publication on their researchers' behalf. More funding agencies are joining the Howard Hughes Medical Institute, the Wellcome Trust, and others... | 15094807_p4 | 15094807 | Publication Charges—Nothing New | 1.146611 | other | Other | [
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] | en | 0.999996 |
Universities, too, are supporting open access directly by setting aside funds for open-access publication through institutional memberships with BMC and PLoS or through discretionary funds that faculty can tap into to pay publication charges. Such approaches reduce authors' reliance on individual grants to support char... | 15094807_p5 | 15094807 | Publication Charges—Nothing New | 1.12351 | other | Other | [
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] | en | 0.999999 |
Even with the steady increase in sources to pay publication fees, detractors claim that open-access publishing may lead to a situation in which some authors are simply unable to publish their work due to lack of funds. The response to this concern is that the ability of authors to pay publication charges must never be ... | 15094807_p6 | 15094807 | The Disenfranchised | 1.120764 | other | Other | [
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] | en | 0.999996 |
In part, the savings to institutions, hospitals, nongovernmental organizations, and universities provided by open-access publications could help to establish funds for researchers who are less well supported. In the developing world, as free online access to scientific literature is increasingly seen as a political imp... | 15094807_p7 | 15094807 | The Disenfranchised | 1.176269 | other | Other | [
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] | [
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] | en | 0.999998 |
Perhaps the real misconception about the unfair burden that open access places on authors resides in the terminology—the term “author charge” is itself misleading. Publication fees are not borne purely by authors, but are shared by the many organizations whose missions depend on the broadest possible dissemination and ... | 15094807_p8 | 15094807 | The Disenfranchised | 1.295525 | other | Other | [
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While so far only one prion protein is known in mammals, several prion-like proteins capable of forming self-propagating aggregates have been found in various yeast species. The common structural feature of yeast prion proteins is the so-called prion domain, characterized by the high content of glutamines (Q) and aspar... | 15094820_p0 | 15094820 | Prion Domains | 4.917628 | biomedical | Study | [
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A remarkable feature of yeast prion proteins is their ability to produce distinct inherited “variants” of the prion. For example, [PSI + ] prion could exist in several distinct forms that suppress termination of translation to different degrees. These “variants” of yeast prions are analogous to different prion “strains... | 15094820_p1 | 15094820 | Inheriting Variations | 4.781038 | biomedical | Study | [
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Although yeast prions have been studied for almost ten years, very little is known about their biological significance. We do not know the functions of the majority of proteins that can exist as prions. Even if a function of prion proteins, such as with Sup35 or Ure2, is known, we do not understand the biological signi... | 15094820_p2 | 15094820 | What Do Prions Do? | 4.412509 | biomedical | Study | [
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Searching genomes of various species demonstrated that a relatively large fraction of proteins (between 0.1% and 2%) contain Q/N-rich domains or polyQ or polyN sequences. These domains are often found in transcription factors, protein kinases, and components of vesicular transport. The Q/N-rich domains usually are not ... | 15094820_p3 | 15094820 | Q/N Does Not Necessarily a Prion Make | 4.711321 | biomedical | Study | [
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The first indication that mammalian proteins with Q/N-rich domains can form self-propagating prions came from recent work with a regulator of translation cytoplasmic polyadenylation element-binding protein (CPEB) from Aplysia neurons . The neuronal form of this protein has a Q/N-rich domain similar to the prion domains... | 15094820_p4 | 15094820 | Q/N Does Not Necessarily a Prion Make | 4.49985 | biomedical | Study | [
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What makes protein aggregates in yeast propagate? The key cellular element that is critical for this process is molecular chaperone Hsp104 . This factor is specifically required for maintenance of all known prions within generations and probably is not involved in prion formation (i.e., initial protein aggregation). [P... | 15094820_p5 | 15094820 | Mystery of Propagation | 4.57072 | biomedical | Study | [
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The fact that some proteins with Q/N-rich domains form self-propagating aggregates, while others can aggregate but cannot form prions, suggests that there should be some structural elements either within the Q/N-rich sequence or close to it that confer the ability to propagate. In an article in this issue of PLoS Biolo... | 15094820_p6 | 15094820 | Mystery of Propagation | 4.349273 | biomedical | Study | [
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The likely possibility was that the oligopeptide repeats could be interchangeable between different prions, leading to creation of novel chimeric prions. In fact, the authors constructed an F chimera, a fusion protein having the N-rich domain of New1 and the oligopeptide repeat of Sup35. This fusion polypeptide efficie... | 15094820_p7 | 15094820 | Mystery of Propagation | 4.545953 | biomedical | Study | [
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Advances in microarray technology have made the systematic study of expression levels of thousands of transcripts possible. This has been heralded as a major step forward in understanding the function of genomes, since transcript expression levels are expected to correlate with biological functions. Although this is cl... | 15138501_p0 | 15138501 | Introduction | 4.90516 | biomedical | Study | [
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To test whether this may be the case, we have investigated whether a neutral model can describe transcriptome differences observed among primate and mouse species as well as among various brain regions within a species. | 15138501_p1 | 15138501 | Introduction | 3.619008 | biomedical | Study | [
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If the majority of evolutionary changes are caused by historical accidents rather than by natural selection, they will accumulate mainly as a function of time rather than as a function of morphological or behavioral change of organisms. Applied to transcriptome evolution, a neutral model therefore implies that the rate... | 15138501_p2 | 15138501 | Transcriptome Evolution among Species | 4.277115 | biomedical | Study | [
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Since oligonucleotide-based microarrays are sensitive to DNA sequence differences and the orangutan and rhesus macaque genome sequences are not yet known—so that we cannot delete oligonucleotides carrying mismatches between the species—we used arrays containing around 28,000 cDNAs ranging in length from 500 to 1,500 nu... | 15138501_p3 | 15138501 | Transcriptome Evolution among Species | 4.134145 | biomedical | Study | [
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In a recent study of gene expression in the brains of humans, chimpanzees, and orangutans, we found that the rate of expression change on the human lineage has been larger than on the chimpanzee lineage . This is in apparent contradiction to the linearity observed here. However, the analysis of Enard et al. was based o... | 15138501_p4 | 15138501 | Transcriptome Evolution among Species | 4.148812 | biomedical | Study | [
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] | en | 0.999999 |
The clocklike accumulation of expression differences between species observed for primates is in agreement with the recent observation that differences in gene expression are consistent with phylogenetic relationships among Drosophila species , and both these observations are compatible with the predictions of the neut... | 15138501_p5 | 15138501 | Transcriptome Evolution among Species | 4.170428 | biomedical | Study | [
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] | en | 0.999994 |
In addition to the clocklike accumulation of evolutionary changes, the neutral theory states that the same forces determine the rate of evolution both within and between species . Thus, a neutral prediction with respect to transcriptome evolution is that genes that vary more within species should be more likely to chan... | 15138501_p6 | 15138501 | Transcriptome Evolution among Species | 4.174745 | biomedical | Study | [
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We further considered the correlation between the average diversity within humans and chimpanzees and the divergence between the species for the 2,926 genes. This correlation is highly significant ( p < 0.001) as gauged by a permutation test ( see Materials and Methods ). Since all array probes that carried sequence di... | 15138501_p7 | 15138501 | Transcriptome Evolution among Species | 4.134356 | biomedical | Study | [
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To investigate whether gene expression differences accumulate as a function of time also in another group of mammals, we analyzed three mouse species. An advantage in this case is that post mortem artifacts are less likely to influence the results than in the case of autopsy material of humans and great apes. We determ... | 15138501_p8 | 15138501 | Transcriptome Evolution among Species | 4.330808 | biomedical | Study | [
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