Genome Biology and Evolution - RSS feed of current content

Welcome to Genome Biology and Evolution

Gojobori, T., Martin, W. — Tue, 05 May 2009 13:24:26 PDT

Independent Mammalian Genome Contractions Following the KT Boundary

Rho, M., Zhou, M., Gao, X., Kim, S., Tang, H., Lynch, M. — Fri, 22 May 2009 06:05:29 PDT

Although it is generally accepted that major changes in the earth's history are significant drivers of phylogenetic diversification and extinction, such episodes may also have long-lasting effects on genomic architecture. Here we show that widespread reductions in genome size have occurred in multiple lineages of mammals subsequent to the Cretaceous–Tertiary (KT) boundary, whereas there is no evidence for such changes in other vertebrate, invertebrate, or land plant lineages. Although the mechanisms remain unclear, such shifts in mammalian genome evolution may be a consequence of an increase in the efficiency of selection against excess DNA resulting from post-KT population size expansions. Independent historical changes in genome architecture in diverse lineages raise a significant challenge to the idea that genome size is finely tuned to achieve adaptive phenotypic modifications and suggest that attempts to use phylogenetic analysis to infer ancestral genome sizes may be problematical.

Evidence That Replication-Associated Mutation Alone Does Not Explain Between-Chromosome Differences In Substitution Rates

Pink, C. J., Swaminathan, S. K., Dunham, I., Rogers, J., Ward, A., Hurst, L. D. — Fri, 22 May 2009 06:05:29 PDT

Since Haldane first noticed an excess of paternally derived mutations, it has been considered that most mutations derive from errors during germ line replication. Miyata et al. (1987) proposed that differences in the rate of neutral evolution on X, Y, and autosome can be employed to measure the extent of this male bias. This commonly applied method assumes replication to be the sole source of between-chromosome variation in substitution rates. We propose a simple test of this assumption: If true, estimates of the male bias should be independent of which two chromosomal classes are compared. Prior evidence from rodents suggested that this might not be true, but conclusions were limited by a lack of rat Y-linked sequence. We therefore sequenced two rat Y-linked bacterial artificial chromosomes and determined evolutionary rate by comparison with mouse. For estimation of rates we consider both introns and synonymous rates. Surprisingly, for both data sets the prediction of congruent estimates of is strongly rejected. Indeed, some comparisons suggest a female bias with autosomes evolving faster than Y-linked sequence. We conclude that the method of Miyata et al. (1987) has the potential to provide incorrect estimates. Correcting the method requires understanding of the other causes of substitution that might differ between chromosomal classes. One possible cause is recombination-associated substitution bias for which we find some evidence. We note that if, as some suggest, this association is dominantly owing to male recombination, the high estimates of seen in birds is to be expected as Z chromosomes recombine in males.

Abundant Indispensable Redundancies in Cellular Metabolic Networks

Wang, Z., Zhang, J. — Fri, 22 May 2009 06:05:29 PDT

Cellular life is a highly redundant complex system; yet, the evolutionary maintenance of the redundancy remains unexplained. Using a systems biology approach, we infer that 37–47% of metabolic reactions in Escherichia coli and yeast can be individually removed without blocking the production of any biomass component under any nutritional condition. However, the majority of these redundant reactions are preserved because they have differential maximal efficiencies at different conditions or their loss causes an immediate fitness reduction that can only be regained via mutation, drift, and selection in evolution. The remaining redundancies are attributable to pleiotropic effects or recent horizontal gene transfers. We find that E. coli and yeast exhibit opposite relationships between the functional importance and redundancy level of a reaction, which is inconsistent with the conjecture that redundancies are preserved as an adaptation to back up important parts in the system. Interestingly, the opposite relationships can both be recapitulated by a simple model in which the natural environments of the organisms change frequently. Thus, adaptive backup is neither necessary nor sufficient to explain the high redundancy of cellular metabolic networks. Taken together, our results strongly suggest that redundant reactions are not kept as backups and that the genetic robustness of metabolic networks is an evolutionary by-product.

On the Origin and Evolution of Vertebrate Olfactory Receptor Genes: Comparative Genome Analysis Among 23 Chordate Species

Niimura, Y. — Fri, 22 May 2009 06:05:29 PDT

Olfaction is a primitive sense in organisms. Both vertebrates and insects have receptors for detecting odor molecules in the environment, but the evolutionary origins of these genes are different. Among studied vertebrates, mammals have ~1,000 olfactory receptor (OR) genes, whereas teleost fishes have much smaller (~100) numbers of OR genes. To investigate the origin and evolution of vertebrate OR genes, I attempted to determine near-complete OR gene repertoires by searching whole-genome sequences of 14 nonmammalian chordates, including cephalochordates (amphioxus), urochordates (ascidian and larvacean), and vertebrates (sea lamprey, elephant shark, five teleost fishes, frog, lizard, and chicken), followed by a large-scale phylogenetic analysis in conjunction with mammalian OR genes identified from nine species. This analysis showed that the amphioxus has >30 vertebrate-type OR genes though it lacks distinctive olfactory organs, whereas all OR genes appear to have been lost in the urochordate lineage. Some groups of genes (, , and ) that are phylogenetically nested within vertebrate OR genes showed few gene gains and losses, which is in sharp contrast to the evolutionary pattern of OR genes, suggesting that they are actually non-OR genes. Moreover, the analysis demonstrated a great difference in OR gene repertoires between aquatic and terrestrial vertebrates, reflecting the necessity for the detection of water-soluble and airborne odorants, respectively. However, a minor group (β) of genes that are atypically present in both aquatic and terrestrial vertebrates was also found. These findings should provide a critical foundation for further physiological, behavioral, and evolutionary studies of olfaction in various organisms.

Coevolution of DNA Uptake Sequences and Bacterial Proteomes

Findlay, W. A., Redfield, R. J. — Fri, 22 May 2009 06:05:29 PDT

Dramatic examples of repeated sequences occur in the genomes of some naturally competent bacteria, which contain hundreds or thousands of copies of short motifs called DNA uptake signal sequences. Here, we analyze the evolutionary interactions between coding-region uptake sequences and the proteomes of Haemophilus influenzae, Actinobacillus pleuropneumoniae, and Neisseria meningitidis. In all three genomes, uptake sequence accumulation in coding sequences has approximately doubled the frequencies of those tripeptides specified by each species’ uptake sequence. The presence of uptake sequences in particular reading frames correlated most strongly with the use of preferred codons at degenerately coded positions, but the density of uptake sequences correlated only poorly with protein functional category. Genes lacking homologs in related genomes also lacked uptake sequences, strengthening the evidence that uptake sequences do not drive lateral gene transfer between distant relatives but instead accumulate after genes have been transferred. Comparison of the uptake sequence-encoded peptides of H. influenzae and N. meningitidis proteins with their homologs from related bacteria without uptake sequences indicated that uptake sequences were also preferentially located in poorly conserved genes and at poorly conserved amino acids. With few exceptions, amino acids at positions encoded by uptake sequences were as well conserved as other amino acids, suggesting that extant uptake sequences impose little or no constraint on coding for protein function. However, this state is likely to be achieved at a substantial cost because of the selective deaths required to eliminate maladaptive mutations that improve uptake sequences.

Footprints of Inversions at Present and Past Pseudoautosomal Boundaries in Human Sex Chromosomes

Fri, 22 May 2009 06:05:29 PDT

The human sex chromosomes have stopped recombining gradually, which has left five evolutionary strata on the X chromosome. Y inversions are thought to have suppressed X–Y recombination but clear evidence is missing. Here, we looked for such evidence by focusing on a region—the X-added region (XAR)—that includes the pseudoautosomal region and the most recent strata 3 to 5. We estimated and analyzed the whole set of parsimonious scenarios of Y inversions given the gene order in XAR and its Y homolog. Comparing these to scenarios for simulated sequences suggests that the strata 4 and 5 were formed by Y inversions. By comparing the X and Y DNA sequences, we found clear evidence of two Y inversions associated with duplications that coincide with the boundaries of strata 4 and 5. Divergence between duplicates is in agreement with the timing of strata 4 and 5 formation. These duplicates show a complex pattern of gene conversion that resembles the pattern previously found for AMELXY, a stratum 3 locus. This suggests that this locus—despite AMELY being unbroken—was possibly involved in a Y inversion that formed stratum 3. However, no clear evidence supporting the formation of stratum 3 by a Y inversion was found, probably because this stratum is too old for such an inversion to be detectable. Our results strongly support the view that the most recent human strata have arisen by Y inversions and suggest that inversions have played a major role in the differentiation of our sex chromosomes.

Locus-Specific Decoupling of Base Composition Evolution at Synonymous Sites and Introns along the Drosophila melanogaster and Drosophila sechellia Lineages

Bauer DuMont, V. L., Singh, N. D., Wright, M. H., Aquadro, C. F. — Wed, 17 Jun 2009 20:37:02 PDT

Selection is thought to be partially responsible for patterns of molecular evolution at synonymous sites within numerous Drosophila species. Recently, "per-site" and likelihood methods have been developed to detect loci for which positive selection is a major component of synonymous site evolution. An underlying assumption of these methods, however, is a homogeneous mutation process. To address this potential shortcoming, we perform a complementary analysis making gene-by-gene comparisons of paired synonymous site and intron substitution rates toward and away from the nucleotides G and C because preferred codons are G or C ending in Drosophila. This comparison may reduce both the false-positive rate (due to broadscale heterogeneity in mutation) and false-negative rate (due to lack of power comparing small numbers of sites) of the per-site and likelihood methods. We detect loci with patterns of evolution suggestive of synonymous site selection pressures predominately favoring unpreferred and preferred codons along the Drosophila melanogaster and Drosophila sechellia lineages, respectively. Intron selection pressures do not appear sufficient to explain all these results as the magnitude of the difference in synonymous and intron evolution is dependent on recombination environment and chromosomal location in a direction supporting the hypothesis of selectively driven synonymous fixations. This comparison identifies 101 loci with an apparent switch in codon preference between D. melanogaster and D. sechellia, a pattern previously only observed at the Notch locus.

Recent amplification and impact of MITEs on the genome of grapevine (Vitis vinifera L.)

Benjak, A., Boue, S., Forneck, A., Casacuberta, J. M. — Mon, 22 Jun 2009 23:28:41 PDT

Miniature inverted-repeat transposable elements (MITEs) are a particular type of defective class II transposons present in genomes as highly homogeneous populations of small elements. Their high copy number and close association to genes make their potential impact on gene evolution particularly relevant. Here, we present a detailed analysis of the MITE families directly related to grapevine "cut-and-paste" transposons. Our results show that grapevine MITEs have transduplicated and amplified genomic sequences, including gene sequences and fragments of other mobile elements. Our results also show that although some of the MITE families were already present in the ancestor of the European and American Vitis wild species, they have been amplified and have been actively transposing accompanying grapevine domestication and breeding. We show that MITEs are abundant in grapevine and some of them are frequently inserted within the untranslated regions of grapevine genes. MITE insertions are highly polymorphic among grapevine cultivars, which frequently generate transcript variability. The data presented here show that MITEs have greatly contributed to the grapevine genetic diversity which has been used for grapevine domestication and breeding.

Measuring Transcription Factor-Binding Site Turnover: A Maximum Likelihood Approach Using Phylogenies

Mon, 22 Jun 2009 23:28:41 PDT

A major mode of gene expression evolution is based on changes in cis-regulatory elements (CREs) whose function critically depends on the presence of transcription factor–binding sites (TFBS). Because CREs experience extensive TFBS turnover even with conserved function, alignment-based studies of CRE sequence evolution are limited to very closely related species. Here, we propose an alternative approach based on a stochastic model of TFBS turnover. We implemented a maximum likelihood model that permits variable turnover rates in different parts of the species tree. This model can be used to detect changes in turnover rate as a proxy for differences in the selective pressures acting on TFBS in different clades. We applied this method to five TFBS in the fungi methionine biosynthesis pathway and three TFBS in the HoxA clusters of vertebrates. We find that the estimated turnover rate is generally high, with half-life ranging between ~5 and 150 My and a mode around tens of millions of years. This rate is consistent with the finding that even functionally conserved enhancers can show very low sequence similarity. We also detect statistically significant differences in the equilibrium densities of estrogen- and progesterone-response elements in the HoxA clusters between mammal and nonmammal vertebrates. Even more extreme clade-specific differences were found in the fungal data. We conclude that stochastic models of TFBS turnover enable the detection of shifts in the selective pressures acting on CREs in different organisms.

The analysis tool, called CRETO (Cis-Regulatory Element Turn-Over) can be downloaded from http://www.bioinf.uni-leipzig.de/Software/creto/.

Analysis of Rare Genomic Changes Does Not Support the Unikont-Bikont Phylogeny and Suggests Cyanobacterial Symbiosis as the Point of Primary Radiation of Eukaryotes

Rogozin, I. B., Basu, M. K., Csuros, M., Koonin, E. V. — Mon, 22 Jun 2009 23:28:41 PDT

The deep phylogeny of eukaryotes is an important but extremely difficult problem of evolutionary biology. Five eukaryotic supergroups are relatively well established but the relationship between these supergroups remains elusive, and their divergence seems to best fit a "Big Bang" model. Attempts were made to root the tree of eukaryotes by using potential derived shared characters such as unique fusions of conserved genes. One popular model of eukaryotic evolution that emerged from this type of analysis is the unikont–bikont phylogeny: The unikont branch consists of Metazoa, Choanozoa, Fungi, and Amoebozoa, whereas bikonts include the rest of eukaryotes, namely, Plantae (green plants, Chlorophyta, and Rhodophyta), Chromalveolata, excavates, and Rhizaria. We reexamine the relationships between the eukaryotic supergroups using a genome-wide analysis of rare genomic changes (RGCs) associated with multiple, conserved amino acids (RGC_CAMs and RGC_CAs), to resolve trifurcations of major eukaryotic lineages. The results do not support the basal position of Chromalveolata with respect to Plantae and unikonts or the monophyly of the bikont group and appear to be best compatible with the monophyly of unikonts and Chromalveolata. Chromalveolata show a distinct, additional signal of affinity with Plantae, conceivably, owing to genes transferred from the secondary, red algal symbiont. Excavates are derived forms, with extremely long branches that complicate phylogenetic inference; nevertheless, the RGC analysis suggests that they are significantly more likely to cluster with the unikont–Chromalveolata assemblage than with the Plantae. Thus, the first split in eukaryotic evolution might lie between photosynthetic and nonphotosynthetic forms and so could have been triggered by the endosymbiosis between an ancestral unicellular eukaryote and a cyanobacterium that gave rise to the chloroplast.

Estimates of Positive Darwinian Selection Are Inflated by Errors in Sequencing, Annotation, and Alignment

Schneider, A., Souvorov, A., Sabath, N., Landan, G., Gonnet, G. H., Graur, D. — Mon, 22 Jun 2009 23:28:41 PDT

Published estimates of the proportion of positively selected genes (PSGs) in human vary over three orders of magnitude. In mammals, estimates of the proportion of PSGs cover an even wider range of values. We used 2,980 orthologous protein-coding genes from human, chimpanzee, macaque, dog, cow, rat, and mouse as well as an established phylogenetic topology to infer the fraction of PSGs in all seven terminal branches. The inferred fraction of PSGs ranged from 0.9% in human through 17.5% in macaque to 23.3% in dog. We found three factors that influence the fraction of genes that exhibit telltale signs of positive selection: the quality of the sequence, the degree of misannotation, and ambiguities in the multiple sequence alignment. The inferred fraction of PSGs in sequences that are deficient in all three criteria of coverage, annotation, and alignment is 7.2 times higher than that in genes with high trace sequencing coverage, "known" annotation status, and perfect alignment scores. We conclude that some estimates on the prevalence of positive Darwinian selection in the literature may be inflated and should be treated with caution.

Calibration of Mutation Rates Reveals Diverse Subfamily Structure of Galliform CR1 Repeats

Liu, G. E., Jiang, L., Tian, F., Zhu, B., Song, J. — Mon, 22 Jun 2009 23:28:41 PDT

Chicken Repeat 1 (CR1) repeats are the most abundant family of repeats in the chicken genome, with more than 200,000 copies accounting for ~80% of the chicken interspersed repeats. CR1 repeats are believed to have arisen from the retrotransposition of a small number of master elements, which gave rise to the 22 CR1 subfamilies as previously reported in Repbase. We performed a global assessment of the divergence distributions, phylogenies, and consensus sequences of CR1 repeats in the chicken genome. We identified and validated 57 chicken CR1 subfamilies and further analyzed the correlation between these subfamilies and their regional GC contents. We also discovered one novel lineage-specific CR1 subfamilies in turkeys when compared with chickens. We built an evolutionary tree of these subfamilies and concluded that CR1 repeats may play an important role in reshaping the structure of bird genomes.

Similarly Strong Purifying Selection Acts on Human Disease Genes of All Evolutionary Ages

Cai, J. J., Borenstein, E., Chen, R., Petrov, D. A. — Mon, 22 Jun 2009 23:28:41 PDT

A number of studies have showed that recently created genes differ from the genes created in deep evolutionary past in many aspects. Here, we determined the age of emergence and propensity for gene loss (PGL) of all human protein–coding genes and compared disease genes with non-disease genes in terms of their evolutionary rate, strength of purifying selection, mRNA expression, and genetic redundancy. The older and the less prone to loss, non-disease genes have been evolving 1.5- to 3-fold slower between humans and chimps than young non-disease genes, whereas Mendelian disease genes have been evolving very slowly regardless of their ages and PGL. Complex disease genes showed an intermediate pattern. Disease genes also have higher mRNA expression heterogeneity across multiple tissues than non-disease genes regardless of age and PGL. Young and middle-aged disease genes have fewer similar paralogs as non-disease genes of the same age. We reasoned that genes were more likely to be involved in human disease if they were under a strong functional constraint, expressed heterogeneously across tissues, and lacked genetic redundancy. Young human genes that have been evolving under strong constraint between humans and chimps might also be enriched for genes that encode important primate or even human-specific functions.

Deletional Bias across the Three Domains of Life

Kuo, C.-H., Ochman, H. — Tue, 14 Jul 2009 00:00:00 PDT

Elevated levels of genetic drift are hypothesized to be a dominant factor that influences genome size evolution across all life-forms. However, increased levels of drift appear to be correlated with genome expansion in eukaryotes but with genome contraction in bacteria, suggesting that these two groups of organisms experience vastly different mutational inputs and selective constraints. To determine the contribution of small insertion and deletion events to the differences in genome organization between eukaryotes and prokaryotes, we systematically surveyed 17 taxonomic groups across the three domains of life. Based on over 5,000 indel events in noncoding regions, we found that deletional events outnumbered insertions in all groups examined. The extent of deletional bias, when measured by the total length of insertions to deletions, revealed a marked disparity between eukaryotes and prokaryotes, whereas the ratio was close to one in the three eukaryotic groups examined, deletions outweighed insertions by at least a factor of 10 in most prokaryotes. Moreover, the strength of deletional bias is associated with the proportion of coding regions in prokaryotic genomes. Considering that genetic drift is a stochastic process and does not discriminate the exact nature of mutations, the degree of bias toward deletions provides an explanation to the differential responses of eukaryotes and prokaryotes to elevated levels of drift. Furthermore, deletional bias, rather than natural selection, is the primary mechanism by which the compact gene packing within most prokaryotic genomes is maintained.

Efficient Sampling of Parsimonious Inversion Histories with Application to Genome Rearrangement in Yersinia

Miklos, I., Darling, A. E. — Tue, 14 Jul 2009 00:00:00 PDT

Inversions are among the most common mutations acting on the order and orientation of genes in a genome, and polynomial-time algorithms exist to obtain a minimal length series of inversions that transform one genome arrangement to another. However, the minimum length series of inversions (the optimal sorting path) is often not unique as many such optimal sorting paths exist. If we assume that all optimal sorting paths are equally likely, then statistical inference on genome arrangement history must account for all such sorting paths and not just a single estimate. No deterministic polynomial algorithm is known to count the number of optimal sorting paths nor sample from the uniform distribution of optimal sorting paths.

Here, we propose a stochastic method that uniformly samples the set of all optimal sorting paths. Our method uses a novel formulation of parallel Markov chain Monte Carlo. In practice, our method can quickly estimate the total number of optimal sorting paths. We introduce a variant of our approach in which short inversions are modeled to be more likely, and we show how the method can be used to estimate the distribution of inversion lengths and breakpoint usage in pathogenic Yersinia pestis.

The proposed method has been implemented in a program called "MC4Inversion." We draw comparison of MC4Inversion to the sampler implemented in BADGER and a previously described importance sampling (IS) technique. We find that on high-divergence data sets, MC4Inversion finds more optimal sorting paths per second than BADGER and the IS technique and simultaneously avoids bias inherent in the IS technique.

High Throughput Genome-Wide Survey of Small RNAs from the Parasitic Protists Giardia intestinalis and Trichomonas vaginalis

Chen, X., Collins, L. J., Biggs, P. J., Penny, D. — Fri, 24 Jul 2009 09:44:27 PDT

RNA interference (RNAi) is a set of mechanisms which regulate gene expression in eukaryotes. Key elements of RNAi are small sense and antisense RNAs from 19 to 26 nt generated from double-stranded RNAs. MicroRNAs (miRNAs) are a major type of RNAi-associated small RNAs and are found in most eukaryotes studied to date. To investigate whether small RNAs associated with RNAi appear to be present in all eukaryotic lineages, and therefore present in the ancestral eukaryote, we studied two deep-branching protozoan parasites, Giardia intestinalis and Trichomonas vaginalis. Little is known about endogenous small RNAs involved in RNAi of these organisms. Using Illumina Solexa sequencing and genome-wide analysis of small RNAs from these distantly related deep-branching eukaryotes, we identified 10 strong miRNA candidates from Giardia and 11 from Trichomonas. We also found evidence of Giardia short-interfering RNAs potentially involved in the expression of variant-specific surface proteins. In addition, eight new small nucleolar RNAs from Trichomonas are identified. Our results indicate that miRNAs are likely to be general in ancestral eukaryotes and therefore are likely to be a universal feature of eukaryotes.

A Complex Suite of Forces Drives Gene Traffic from Drosophila X Chromosomes

Meisel, R. P., Han, M. V., Hahn, M. W. — Fri, 31 Jul 2009 13:03:19 PDT

Theoretical studies predict X chromosomes and autosomes should be under different selection pressures, and there should therefore be differences in sex-specific and sexually antagonistic gene content between the X and the autosomes. Previous analyses have identified an excess of genes duplicated by retrotransposition from the X chromosome in Drosophila melanogaster. A number of hypotheses may explain this pattern, including mutational bias, escape from X-inactivation during spermatogenesis, and the movement of male-favored (sexually antagonistic) genes from a chromosome that is predominantly carried by females. To distinguish among these processes and to examine the generality of these patterns, we identified duplicated genes in nine sequenced Drosophila genomes. We find that, as in D. melanogaster, there is an excess of genes duplicated from the X chromosome across the genus Drosophila. This excess duplication is due almost completely to genes duplicated by retrotransposition, with little to no excess from the X among genes duplicated via DNA intermediates. The only exception to this pattern appears within the burst of duplication that followed the creation of the Drosophila pseudoobscura neo-X chromosome. Additionally, we examined genes relocated among chromosomal arms (i.e., genes duplicated to new locations coupled with the loss of the copy in the ancestral locus) and found an excess of genes relocated off the ancestral X and neo-X chromosomes. Interestingly, many of the same genes were duplicated or relocated from the independently derived neo-X chromosomes of D. pseudoobscura and Drosophila willistoni, suggesting that natural selection favors the traffic of genes from X chromosomes. Overall, we find that the forces driving gene duplication from X chromosomes are dependent on the lineage in question, the molecular mechanism of duplication considered, the preservation of the ancestral copy, and the age of the X chromosome.

Long-Range Bidirectional Strand Asymmetries Originate at CpG Islands in the Human Genome

Polak, P., Arndt, P. F. — Thu, 06 Aug 2009 08:30:01 PDT

In the human genome, CpG islands (CGIs), which are GC- and CpG-rich sequences, are associated with transcription starting sites (TSSs); in addition, there is evidence that CGIs harbor origins of bidirectional replication (OBRs) and are preferred sites for heteroduplex formation during recombination. Transcription, replication, and recombination processes are known to induce specific mutational patterns in various genomes, and therefore, these patterns are expected to be found around CGIs. We use triple alignments of human, chimp, and macaque to compute the rates of nucleotide substitutions in up to 1 Mbps long intergenic regions on both sides of CGIs. Our analysis revealed that around a CGI there is an asymmetry between complementary substitution rates that is similar to the one that found around the OBR in bacteria. We hypothesize that these asymmetries are induced by differences in the replication of the leading and lagging strand and that a significant number of CGIs overlap OBRs. Within CGIs, we observed a mutational signature of GC-biased gene conversion that is associated with recombination. We suggest that recombination has played a major role in the creation of CGIs.

Protein Subcellular Relocalization in the Evolution of Yeast Singleton and Duplicate Genes

Qian, W., Zhang, J. — Thu, 06 Aug 2009 08:30:02 PDT

Gene duplication is the primary source of new genes, but the mechanisms underlying the functional divergence and retention of duplicate genes are not well understood. Because eukaryotic proteins are localized to subcellular structures and localization can be altered by a single amino acid replacement, it was recently proposed that protein subcellular relocalization (PSR) plays an important role in the functional divergence and retention of duplicate genes. Although numerous examples of distinct subcellular localizations of paralogous proteins have been reported, it is unknown whether PSR occurs more frequently after gene duplication than without duplication. By analyzing experimentally determined and computationally predicted genome-wide protein subcellular localization data of the budding yeast Saccharomyces cerevisiae and two other fungi (Schizosaccharomyces pombe and Kluyveromyces waltii), we show that even singleton genes have an appreciable rate of relocalization in evolution and that duplicate genes do not relocalize more frequently than singletons. These results suggest that subcellular relocalization is unlikely to have been a major mechanism for duplicate gene retention and functional divergence at the genomic scale.

Exploring Repetitive DNA Landscapes Using REPCLASS, a Tool That Automates the Classification of Transposable Elements in Eukaryotic Genomes

Feschotte, C., Keswani, U., Ranganathan, N., Guibotsy, M. L., Levine, D. — Wed, 12 Aug 2009 08:26:26 PDT

Eukaryotic genomes contain large amount of repetitive DNA, most of which is derived from transposable elements (TEs). Progress has been made to develop computational tools for ab initio identification of repeat families, but there is an urgent need to develop tools to automate the annotation of TEs in genome sequences. Here we introduce REPCLASS, a tool that automates the classification of TE sequences. Using control repeat libraries, we show that the program can classify accurately virtually any known TE types. Combining REPCLASS to ab initio repeat finding in the genomes of Caenorhabditis elegans and Drosophila melanogaster allowed us to recover the contrasting TE landscape characteristic of these species. Unexpectedly, REPCLASS also uncovered several novel TE families in both genomes, augmenting the TE repertoire of these model species. When applied to the genomes of distant Caenorhabditis and Drosophila species, the approach revealed a remarkable conservation of TE composition profile within each genus, despite substantial interspecific covariations in genome size and in the number of TEs and TE families. Lastly, we applied REPCLASS to analyze 10 fungal genomes from a wide taxonomic range, most of which have not been analyzed for TE content previously. The results showed that TE diversity varies widely across the fungi "kingdom" and appears to positively correlate with genome size, in particular for DNA transposons. Together, these data validate REPCLASS as a powerful tool to explore the repetitive DNA landscapes of eukaryotes and to shed light onto the evolutionary forces shaping TE diversity and genome architecture.

Evolutionary Insights on C4 Photosynthetic Subtypes in Grasses from Genomics and Phylogenetics

Christin, P.-A., Samaritani, E., Petitpierre, B., Salamin, N., Besnard, G. — Thu, 13 Aug 2009 14:35:53 PDT

In plants, an oligogene family encodes NADP-malic enzymes (NADP-me), which are responsible for various functions and exhibit different kinetics and expression patterns. In particular, a chloroplast isoform of NADP-me plays a key role in one of the three biochemical subtypes of C₄ photosynthesis, an adaptation to warm environments that evolved several times independently during angiosperm diversification. By combining genomic and phylogenetic approaches, this study aimed at identifying the molecular mechanisms linked to the recurrent evolutions of C₄-specific NADP-me in grasses (Poaceae). Genes encoding NADP-me (nadpme) were retrieved from genomes of model grasses and isolated from a large sample of C₃ and C₄ grasses. Genomic and phylogenetic analyses showed that 1) the grass nadpme gene family is composed of four main lineages, one of which is expressed in plastids (nadpme-IV), 2) C₄-specific NADP-me evolved at least five times independently from nadpme-IV, and 3) some codons driven by positive selection underwent parallel changes during the multiple C₄ origins. The C₄ NADP-me being expressed in chloroplasts probably constrained its recurrent evolutions from the only plastid nadpme lineage and this common starting point limited the number of evolutionary paths toward a C₄ optimized enzyme, resulting in genetic convergence. In light of the history of nadpme genes, an evolutionary scenario of the C₄ phenotype using NADP-me is discussed.

Large-Scale Phylogenomic Analyses Reveal That Two Enigmatic Protist Lineages, Telonemia and Centroheliozoa, Are Related to Photosynthetic Chromalveolates

Thu, 13 Aug 2009 14:35:53 PDT

Understanding the early evolution and diversification of eukaryotes relies on a fully resolved phylogenetic tree. In recent years, most eukaryotic diversity has been assigned to six putative supergroups, but the evolutionary origin of a few major "orphan" lineages remains elusive. Two ecologically important orphan groups are the heterotrophic Telonemia and Centroheliozoa. Telonemids have been proposed to be related to the photosynthetic cryptomonads or stramenopiles and centrohelids to haptophytes, but molecular phylogenies have failed to provide strong support for any phylogenetic hypothesis. Here, we investigate the origins of Telonema subtilis (a telonemid) and Raphidiophrys contractilis (a centrohelid) by large-scale 454 pyrosequencing of cDNA libraries and including new genomic data from two cryptomonads (Guillardia theta and Plagioselmis nannoplanctica) and a haptophyte (Imantonia rotunda). We demonstrate that 454 sequencing of cDNA libraries is a powerful and fast method of sampling a high proportion of protist genes, which can yield ample information for phylogenomic studies. Our phylogenetic analyses of 127 genes from 72 species indicate that telonemids and centrohelids are members of an emerging major group of eukaryotes also comprising cryptomonads and haptophytes. Furthermore, this group is possibly closely related to the SAR clade comprising stramenopiles (heterokonts), alveolates, and Rhizaria. Our results link two additional heterotrophic lineages to the predominantly photosynthetic chromalveolate supergroup, providing a new framework for interpreting the evolution of eukaryotic cell structures and the diversification of plastids.

Genome Sequence and Comparative Genome Analysis of Lactobacillus casei: Insights into Their Niche-Associated Evolution

Cai, H., Thompson, R., Budinich, M. F., Broadbent, J. R., Steele, J. L. — Mon, 17 Aug 2009 12:17:48 PDT

Lactobacillus casei is remarkably adaptable to diverse habitats and widely used in the food industry. To reveal the genomic features that contribute to its broad ecological adaptability and examine the evolution of the species, the genome sequence of L. casei ATCC 334 is analyzed and compared with other sequenced lactobacilli. This analysis reveals that ATCC 334 contains a high number of coding sequences involved in carbohydrate utilization and transcriptional regulation, reflecting its requirement for dealing with diverse environmental conditions. A comparison of the genome sequences of ATCC 334 to L. casei BL23 reveals 12 and 19 genomic islands, respectively. For a broader assessment of the genetic variability within L. casei, gene content of 21 L. casei strains isolated from various habitats (cheeses, n = 7; plant materials, n = 8; and human sources, n = 6) was examined by comparative genome hybridization with an ATCC 334-based microarray. This analysis resulted in identification of 25 hypervariable regions. One of these regions contains an overrepresentation of genes involved in carbohydrate utilization and transcriptional regulation and was thus proposed as a lifestyle adaptation island. Differences in L. casei genome inventory reveal both gene gain and gene decay. Gene gain, via acquisition of genomic islands, likely confers a fitness benefit in specific habitats. Gene decay, that is, loss of unnecessary ancestral traits, is observed in the cheese isolates and likely results in enhanced fitness in the dairy niche. This study gives the first picture of the stable versus variable regions in L. casei and provides valuable insights into evolution, lifestyle adaptation, and metabolic diversity of L. casei.

Evolution of Olfactory Receptor Genes in Primates Dominated by Birth-and-Death Process

Dong, D., He, G., Zhang, S., Zhang, Z. — Thu, 20 Aug 2009 11:06:41 PDT

Olfactory receptor (OR) is a large family of G protein–coupled receptors that can detect odorant in order to generate the sense of smell. They constitute one of the largest multiple gene families in animals including primates. To better understand the variation in odor perception and evolution of OR genes among primates, we computationally identified OR gene repertoires in orangutans, marmosets, and mouse lemurs and investigated the birth-and-death process of OR genes in the primate lineage. The results showed that 1) all the primate species studied have no more than 400 intact OR genes, fewer than rodents and canine; 2) Despite the similar number of OR genes in the genome, the makeup of the OR gene repertoires between different primate species is quite different as they had undergone dramatic birth-and-death evolution with extensive gene losses in the lineages leading to current species; 3) Apes and Old World monkey (OWM) have similar fraction of pseudogenes, whereas New World monkey (NWM) have fewer pseudogenes. To measure the selective pressure that had affected the OR gene repertoires in primates, we compared the ratio of nonsynonymous with synonymous substitution rates by using 70 one-to-one orthologous quintets among five primate species. We found that OR genes showed relaxed selective constraints in apes (humans, chimpanzees, and orangutans) than in OWMs (macaques) and NWMs (marmosets). We concluded that OR gene repertoires in primates have evolved in such a way to adapt to their respective living environments. Differential selective constraints might play important role in the primate OR gene evolution in each primate species.

Origin and Diversification of Land Plant CC-Type Glutaredoxins

Ziemann, M., Bhave, M., Zachgo, S. — Fri, 21 Aug 2009 11:29:35 PDT

Glutaredoxins (GRXs) are ubiquitous glutathione-dependent oxidoreductase enzymes implicated in redox homeostasis, particularly oxidative stress response. Three major classes of GRX genes exist, the CPYC, CGFS classes are present in all pro- and eukaryote species, whereas the CC-type class GRXs are specific to land plants. In the basal land plant Physcomitrella patens, only two CC-type GRXs are present, compared with 21 in Arabidopsis. In contrast, sizes of the CPYC and CGFS classes remained rather similar throughout plant evolution, raising the interesting question as to when the CC-type GRXs first originated and how and why they expanded during land plant evolution. Recent evidence suggests that CC-type GRXs may have been recruited during evolution into diverse plant-specific functions of flower development (ROXY1, ROXY2) and pathogenesis response (ROXY19/GRX480). In the present study, GRX genes from the genomes of a range of green algae and evolutionarily diverse land plant species were identified; Ostreococcus, Micromonas, Volvox, Selaginella, Vitis, Sorghum, and Brachypodium. Previously identified sequences from Chlamydomonas, Physcomitrella, Oryza, Arabidopsis, and Populus were integrated to generate a more comprehensive understanding of the forces behind the evolution of various GRX classes. The analysis indicates that the CC-type GRXs probably arose by diversification from the CPYC class, at a time coinciding with colonization of land by plants. This strong differential expansion of the CC-type class occurred exclusively in the angiosperms, mainly through paleopolyploidy duplication events shortly after the monocot–eudicot split, and more recently through multiple tandem duplications that occurred independently in five investigated angiosperm lineages. The presented data suggest that following duplications, subfunctionalization, and subsequent neofunctionalization likely facilitated the sequestration of land plant-specific CC-type GRXs into novel functions such as development and pathogenesis response.

Evolution of the Mitochondrial Genomes of Gall Midges (Diptera: Cecidomyiidae): Rearrangement and Severe Truncation of tRNA Genes

Beckenbach, A. T., Joy, J. B. — Fri, 21 Aug 2009 11:29:35 PDT

We determined the complete mitochondrial genome sequences of two species of gall midges (Diptera: Cecidomyiidae), as well as partial sequence from a third cecidomyiid and a species from a related family, the Sciaridae. The sciarid sequence has a number of rearrangements of tRNA genes, relative to other dipterans, but is otherwise unremarkable. In contrast, the cecidomyiid genomes possess a number of very unusual features. First, the two complete sequences are very small compared with other dipteran mitochondrial genomes. The genome of Mayetiola destructor is only 14,759 bp while that of Rhopalomyia pomum is only 14,503 bp, comparable with genome sizes observed in some arachnids. Second, all three cecidomyiid species have very high A + T content—more than 83% for the coding region. Third, all three cecidomyiid species possess a number of rearrangements of tRNA genes, including variations within the family. Fourth, the most extraordinary feature of cecidomyiids examined in this study is an extreme truncation of all tRNA genes, including the loss of TC arms and apparent absence of the 3' part of the aminoacyl stems.

The truncated tRNA genes of cecidomyiids are very similar to those previously reported for spiders and appear to represent a second, independent origin of these structural features. It is likely that they are made functional through RNA editing, perhaps using the 5' end of the aminoacyl stem as a template for the construction of the required 3' end.

Nucleotide Substitution Bias within the Genus Drosophila Affects the Pattern of Proteome Evolution

Albu, M., Min, X. J., Golding, G. B., Hickey, D. — Fri, 21 Aug 2009 11:29:35 PDT

The availability of complete genome sequences for 12 Drosophila species provides an unprecedented resource for large-scale studies of genome evolution. In this study, we looked for correlated shifts in the patterns of genome and proteome evolution within the genus Drosophila. Specifically, we asked if the nucleotide composition of the Drosophila willistoni genome—which is significantly less GC rich than the other 11 sequenced Drosophila genomes—is reflected in an altered pattern of amino acid substitutions in the encoded proteins. Our results show that this is indeed the case: There are large and highly significant asymmetries in the patterns of amino acid substitution between D. willistoni and Drosophila melanogaster, and they are in the direction predicted by the nucleotide biases. The implication of this result, combined with previous studies on long-term proteome evolution, is that substitutional biases at the DNA level can be a major factor in determining both the long-term and the short-term directions of proteome evolution.

High-Resolution Mapping of Evolutionary Trajectories in a Phage

Dickins, B., Nekrutenko, A. — Wed, 02 Sep 2009 12:13:56 PDT

Experimental evolution in rapidly reproducing viruses offers a robust means to infer substitution trajectories during evolution. But with conventional approaches, this inference is limited by how many individual genotypes can be sampled from the population at a time. Low-frequency changes are difficult to detect, potentially rendering early stages of adaptation unobservable. Here we circumvent this using short-read sequencing technology in a fine-grained analysis of polymorphism dynamics in the sentinel organism: a single-stranded DNA phage X174. Nucleotide differences were educed from noise with binomial filtering methods that harnessed quality scores and separate data from brief phage amplifications. Remarkably, a significant degree of variation was observed in all samples including those grown in brief 2-h cultures. Sites previously reported as subject to high-frequency polymorphisms over a course of weeks exhibited monotonic increases in polymorphism frequency within hours in this study. Additionally, even with limitations imposed by the short length of sequencing reads, we were able to observe statistically significant linkage among polymorphic sites in evolved lineages. Additional parallels between replicate lineages were apparent in the sharing of polymorphic sites and in correlated polymorphism frequencies. Missense mutations were more likely to occur than silent mutations. This study offers the first glimpse into "real-time" substitution dynamics and offers a robust conceptual framework for future viral resequencing studies.

Nonlinear Dynamics of Nonsynonymous (dN) and Synonymous (dS) Substitution Rates Affects Inference of Selection

Wolf, J. B. W., Kunstner, A., Nam, K., Jakobsson, M., Ellegren, H. — Fri, 04 Sep 2009 13:20:05 PDT

Selection modulates gene sequence evolution in different ways by constraining potential changes of amino acid sequences (purifying selection) or by favoring new and adaptive genetic variants (positive selection). The number of nonsynonymous differences in a pair of protein-coding sequences can be used to quantify the mode and strength of selection. To control for regional variation in substitution rates, the proportionate number of nonsynonymous differences (d_N) is divided by the proportionate number of synonymous differences (d_S). The resulting ratio (d_N/d_S) is a widely used indicator for functional divergence to identify particular genes that underwent positive selection. With the ever-growing amount of genome data, summary statistics like mean d_N/d_S allow gathering information on the mode of evolution for entire species. Both applications hinge on the assumption that d_S and mean d_S (~branch length) are neutral and adequately control for variation in substitution rates across genes and across organisms, respectively. We here explore the validity of this assumption using empirical data based on whole-genome protein sequence alignments between human and 15 other vertebrate species and several simulation approaches. We find that d_N/d_S does not appropriately reflect the action of selection as it is strongly influenced by its denominator (d_S). Particularly for closely related taxa, such as human and chimpanzee, d_N/d_S can be misleading and is not an unadulterated indicator of selection. Instead, we suggest that inconsistencies in the behavior of d_N/d_S are to be expected and highlight the idea that this behavior may be inherent to taking the ratio of two randomly distributed variables that are nonlinearly correlated. New null hypotheses will be needed to adequately handle these nonlinear dynamics.

On Reconciling Single and Recurrent Hitchhiking Models

Jensen, J. D. — Fri, 18 Sep 2009 07:41:13 PDT

A major focus of modern population genetics involves using polymorphism data in order to identify regions impacted by recent positive selection (so-called genomic scans). Recently, methodology has been proposed not to identify individual loci, but rather to quantify genomic recurrent hitchhiking (RHH) parameters using this same type of polymorphism data. I here examine to what extent genomic scans for adaptively important loci may be informed by recently estimated RHH parameters (and vice versa). I find that published results are largely incompatible with one another, with approximately an order of magnitude more sweeps being empirically identified than would be predicted under RHH estimates. Results demonstrate that making this connection between SHH and RHH models is crucial for a more complete and accurate characterization of adaptive evolution.

Intertwined Evolutionary Histories of Marine Synechococcus and Prochlorococcus marinus

Zhaxybayeva, O., Doolittle, W. F., Papke, R. T., Gogarten, J. P. — Wed, 23 Sep 2009 06:21:33 PDT

Prochlorococcus is a genus of marine cyanobacteria characterized by small cell and genome size, an evolutionary trend toward low GC content, the possession of chlorophyll b, and the absence of phycobilisomes. Whereas many shared derived characters define Prochlorococcus as a clade, many genome-based analyses recover them as paraphyletic, with some low-light adapted Prochlorococcus spp. grouping with marine Synechococcus. Here, we use 18 Prochlorococcus and marine Synechococcus genomes to analyze gene flow within and between these taxa. We introduce embedded quartet scatter plots as a tool to screen for genes whose phylogeny agrees or conflicts with the plurality phylogenetic signal, with accepted taxonomy and naming, with GC content, and with the ecological adaptation to high and low light intensities. We find that most gene families support high-light adapted Prochlorococcus spp. as a monophyletic clade and low-light adapted Prochlorococcus sp. as a paraphyletic group. But we also detect 16 gene families that were transferred between high-light adapted and low-light adapted Prochlorococcus sp. and 495 gene families, including 19 ribosomal proteins, that do not cluster designated Prochlorococcus and Synechococcus strains in the expected manner. To explain the observed data, we propose that frequent gene transfer between marine Synechococcus spp. and low-light adapted Prochlorococcus spp. has created a "highway of gene sharing" (Beiko RG, Harlow TJ, Ragan MA. 2005. Highways of gene sharing in prokaryotes. Proc Natl Acad Sci USA. 102:14332–14337) that tends to erode genus boundaries without erasing the Prochlorococcus-specific ecological adaptations.

Protein Rates of Evolution Are Predicted by Double-Strand Break Events, Independent of Crossing-over Rates

Weber, C. C., Hurst, L. D. — Wed, 23 Sep 2009 06:21:34 PDT

Theory predicts that, owing to reduced Hill–Robertson interference, genomic regions with high crossing-over rates should experience more efficient selection. In Saccharomyces cerevisiae a negative correlation between the local recombination rate, assayed as meiotic double-strand breaks (DSBs), and the local rate of protein evolution has been considered consistent with such a model. Although DSBs are a prerequisite for crossing-over, they need not result in crossing-over. With recent high-resolution crossover data, we now return to this issue comparing two species of yeast. Strikingly, even allowing for crossover rates, both the rate of premeiotic DSBs and of noncrossover recombination events predict a gene's rate of evolution. This both questions the validity of prior analyses and strongly suggests that any correlation between crossover rates and rates of protein evolution could be owing to slow-evolving genes being prone to DSBs or a direct effect of DSBs on sequence evolution. To ask if classical theory of recombination has any relevance, we determine whether crossover rates predict rates of protein evolution, controlling for noncrossover DSB events, gene ontology (GO) class, gene expression, protein abundance, nucleotide content, and dispensability. We find that genes with high crossing-over rates have low rates of protein evolution after such control, although any correlation is weaker than that previously reported considering meiotic DSBs as a proxy. The data are consistent both with recombination enhancing the efficiency of purifying selection and, independently, with DSBs being associated with low rates of evolution.

Fragile Genomic Sites Are Associated with Origins of Replication

Di Rienzi, S. C., Collingwood, D., Raghuraman, M. K., Brewer, B. J. — Mon, 05 Oct 2009 07:23:10 PDT

Genome rearrangements are mediators of evolution and disease. Such rearrangements are frequently bounded by transfer RNAs (tRNAs), transposable elements, and other repeated elements, suggesting a functional role for these elements in creating or repairing breakpoints. Though not well explored, there is evidence that origins of replication also colocalize with breakpoints. To investigate a potential correlation between breakpoints and origins, we analyzed evolutionary breakpoints defined between Saccharomyces cerevisiae and Kluyveromyces waltii and S. cerevisiae and a hypothetical ancestor of both yeasts, as well as breakpoints reported in the experimental literature. We find that origins correlate strongly with both evolutionary breakpoints and those described in the literature. Specifically, we find that origins firing earlier in S phase are more strongly correlated with breakpoints than are later-firing origins. Despite origins being located in genomic regions also bearing tRNAs and Ty elements, the correlation we observe between origins and breakpoints appears to be independent of these genomic features. This study lays the groundwork for understanding the mechanisms by which origins of replication may impact genome architecture and disease.

Phylogenomics of Sterol Synthesis: Insights into the Origin, Evolution, and Diversity of a Key Eukaryotic Feature

Desmond, E., Gribaldo, S. — Tue, 20 Oct 2009 08:30:20 PDT

The availability of complete genomes from a wide sampling of eukaryotic diversity has allowed the application of phylogenomics approaches to study the origin and evolution of unique eukaryotic cellular structures, but these are still poorly applied to study unique eukaryotic metabolic pathways. Sterols are a good example because they are an essential feature of eukaryotic membranes. The sterol pathway has been well dissected in vertebrates, fungi, and land plants. However, although different types of sterols have been identified in other eukaryotic lineages, their pathways have not been fully characterized. We have carried out an extensive analysis of the taxonomic distribution and phylogeny of the enzymes of the sterol pathway in a large sampling of eukaryotic lineages. This allowed us to tentatively indicate features of the sterol pathway in organisms where this has not been characterized and to point out a number of steps for which yet-to-discover enzymes may be at work. We also inferred that the last eukaryotic common ancestor already harbored a large panel of enzymes for sterol synthesis and that subsequent evolution over the eukaryotic tree occurred by tinkering, mainly by gene losses. We highlight a high capacity of sterol synthesis in the myxobacterium Plesiocystis pacifica, and we support the hypothesis that the few bacteria that harbor homologs of the sterol pathway have likely acquired these via horizontal gene transfer from eukaryotes. Finally, we propose a potential candidate for the elusive enzyme performing C-3 ketoreduction (ERG27 equivalent) in land plants and probably in other eukaryotic phyla.

A Universal Nonmonotonic Relationship between Gene Compactness and Expression Levels in Multicellular Eukaryotes

Carmel, L., Koonin, E. V. — Tue, 20 Oct 2009 08:30:20 PDT

Analysis of gene architecture and expression levels of four organisms, Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, and Arabidopsis thaliana, reveals a surprising, nonmonotonic, universal relationship between expression level and gene compactness. With increasing expression level, the genes tend at first to become longer but, from a certain level of expression, they become more and more compact, resulting in an approximate bell-shaped dependence. There are two leading hypotheses to explain the compactness of highly expressed genes. The selection hypothesis predicts that gene compactness is predominantly driven by the level of expression, whereas the genomic design hypothesis predicts that expression breadth across tissues is the driving force. We observed the connection between gene expression breadth in humans and gene compactness to be significantly weaker than the connection between expression level and compactness, a result that is compatible with the selection hypothesis but not the genome design hypothesis. The initial gene elongation with increasing expression level could be explained, at least in part, by accumulation of regulatory elements enhancing expression, in particular, in introns. This explanation is compatible with the observed positive correlation between intron density and expression level of a gene. Conversely, the trend toward increasing compactness for highly expressed genes could be caused by selection for minimization of energy and time expenditure during transcription and splicing and for increased fidelity of transcription, splicing, and/or translation that is likely to be particularly critical for highly expressed genes. Regardless of the exact nature of the forces that shape the gene architecture, we present evidence that, at least, in animals, coding and noncoding parts of genes show similar architectonic trends.

Paleopolyploidy in the Brassicales: Analyses of the Cleome Transcriptome Elucidate the History of Genome Duplications in Arabidopsis and Other Brassicales

Barker, M. S., Vogel, H., Schranz, M. E. — Tue, 03 Nov 2009 09:45:55 PST

The analysis of the Arabidopsis genome revealed evidence of three ancient polyploidy events in the evolution of the Brassicaceae, but the exact phylogenetic placement of these events is still not resolved. The most recent event is called the At- (alpha) or 3R, the intermediate event is referred to as the At-β (beta) or 2R, and the oldest is the At- (gamma) or 1R. It has recently been established that At- is shared with other Rosids, including papaya (Carica), poplar (Populus), and grape (Vitis), whereas data to date suggest that At- is Brassicaceae specific. To address more precisely when the At- and At-β events occurred and which plant lineages share these paleopolyploidizations, we sequenced and analyzed over 4,700 normalized expressed sequence tag sequences from the Cleomaceae, the sister family to the Brassicaceae. Analysis of these Cleome data with homologous sequences from other Rosid genomes (Arabidopsis, Carica, Gossypium, Populus, and Vitis) yielded three major findings: 1) confirmation of a Cleome-specific paleopolyploidization (Cs-) that is independent of the Brassicaceae At- paleopolyploidization; 2) Cleome and Arabidopsis share the At-β duplication, which is lacking from papaya within the Brassicales; and 3) rates of molecular evolution are faster for the herbaceous annual taxa Arabidopsis and Cleome than the other predominantly woody perennial Rosid lineages. These findings contribute to our understanding of the dynamics of genome duplication and evolution within one of the most comprehensively surveyed clades of plants, the Rosids, and clarify the complex history of the At-, At-β, and At- duplications of Arabidopsis.

The Evolution of Reduced Microbial Killing

Vriezen, J. A. C., Valliere, M., Riley, M. A. — Tue, 17 Nov 2009 09:35:38 PST

Bacteria engage in a never-ending arms race in which they compete for limited resources and niche space. The outcome of this intense interaction is the evolution of a powerful arsenal of biological weapons. Perhaps the most studied of these are colicins, plasmid-based toxins produced by and active against Escherichia coli. The present study was designed to explore the molecular responses of a colicin-producing strain during serial transfer evolution. What evolutionary changes occur when colicins are produced with no target present? Can killing ability be maintained in the absence of a target? To address these, and other, questions, colicinogenic strains and a noncolicinogenic ancestor were evolved for 253 generations. Samples were taken throughout the experiment and tested for killing ability. By the 38th transfer, a decreased killing ability and an increase in fitness were observed in the colicin-producing strains. Surprisingly, DNA sequence determination of the colicin plasmids revealed no changes in plasmid sequences. However, a set of chromosomally encoded loci experienced changes in gene expression that were positively associated with the reduction in killing. The most significant expression changes were observed in DNA repair genes (which were downregulated in the evolved strains), Mg ion uptake genes (which were upregulated), and late prophage genes (which were upregulated). These results indicate a fine-tuned response to the evolutionary pressures of colicin production, with far more genes involved than had been anticipated.

Evolutionary Persistence of Functional Compensation by Duplicate Genes in Arabidopsis

Hanada, K., Kuromori, T., Myouga, F., Toyoda, T., Li, W.-H., Shinozaki, K. — Wed, 18 Nov 2009 05:40:23 PST

Knocking out a gene from a genome often causes no phenotypic effect. This phenomenon has been explained in part by the existence of duplicate genes. However, it was found that in mouse knockout data duplicate genes are as essential as singleton genes. Here, we study whether it is also true for the knockout data in Arabidopsis. From the knockout data in Arabidopsis thaliana obtained in our study and in the literature, we find that duplicate genes show a significantly lower proportion of knockout effects than singleton genes. Because the persistence of duplicate genes in evolution tends to be dependent on their phenotypic effect, we compared the ages of duplicate genes whose knockout mutants showed less severe phenotypic effects with those with more severe effects. Interestingly, the latter group of genes tends to be more anciently duplicated than the former group of genes. Moreover, using multiple-gene knockout data, we find that functional compensation by duplicate genes for a more severe phenotypic effect tends to be preserved by natural selection for a longer time than that for a less severe effect. Taken together, we conclude that duplicate genes contribute to genetic robustness mainly by preserving compensation for severe phenotypic effects in A. thaliana.

Scanning for the Signatures of Positive Selection for Human-Specific Insertions and Deletions

Chen, C.-H., Chuang, T.-J., Liao, B.-Y., Chen, F.-C. — Mon, 23 Nov 2009 11:23:32 PST

Human-specific small insertions and deletions (HS indels, with lengths <100 bp) are reported to be ubiquitous in the human genome. However, whether these indels contribute to human-specific traits remains unclear. Here we employ a modified McDonald–Kreitman (MK) test and a combinatorial population genetics approach to infer, respectively, the occurrence of positive selection and recent selective sweep events associated with HS indels. We first extract 625,890 HS indels from the human–chimpanzee–macaque–mouse multiple alignments and classify them into nonpolymorphic (41%) and polymorphic (59%) indels with reference to the human indel polymorphism data. The modified MK test is then applied to 100-kb partially overlapped sliding windows across the human genome to scan for the signs of positive selection. After excluding the possibility of biased gene conversion and controlling for false discovery rate, we show that HS indels are potentially positively selected in about 10 Mb of the human genome. Furthermore, the indel-associated positively selected regions overlap with genes more often than expected. However, our result suggests that the potential targets of positive selection are located in noncoding regions. Meanwhile, we also demonstrate that the genomic regions surrounding HS indels are more frequently involved in recent selective sweep than the other regions. In addition, HS indels are associated with distinct recent selective sweep events in different human subpopulations. Our results suggest that HS indels may have been associated with human adaptive changes at both the species level and the subpopulation level.

Evolutionarily Stable Association of Intronic snoRNAs and microRNAs with Their Host Genes

Hoeppner, M. P., White, S., Jeffares, D. C., Poole, A. M. — Mon, 23 Nov 2009 11:23:32 PST

Small nucleolar RNAs (snoRNAs) and microRNAs (miRNAs) are integral to a range of processes, including ribosome biogenesis and gene regulation. Some are intron encoded, and this organization may facilitate coordinated coexpression of host gene and RNA. However, snoRNAs and miRNAs are known to be mobile, so intron-RNA associations may not be evolutionarily stable. We have used genome alignments across 11 mammals plus chicken to examine positional orthology of snoRNAs and miRNAs and report that 21% of annotated snoRNAs and 11% of miRNAs are positionally conserved across mammals. Among RNAs traceable to the bird–mammal common ancestor, 98% of snoRNAs and 76% of miRNAs are intronic. Comparison of the most evolutionarily stable mammalian intronic snoRNAs with those positionally conserved among primates reveals that the former are more overrepresented among host genes involved in translation or ribosome biogenesis and are more broadly and highly expressed. This stability is likely attributable to a requirement for overlap between host gene and intronic snoRNA expression profiles, consistent with an ancestral role in ribosome biogenesis. In contrast, whereas miRNA positional conservation is comparable to that observed for snoRNAs, intronic miRNAs show no obvious association with host genes of a particular functional category, and no statistically significant differences in host gene expression are found between those traceable to mammalian or primate ancestors. Our results indicate evolutionarily stable associations of numerous intronic snoRNAs and miRNAs and their host genes, with probable continued diversification of snoRNA function from an ancestral role in ribosome biogenesis.