60后我在paleopolyploid棉subgenomes持续进化

The importance of whole-genome multiplication (WGM) in plant evolution has long been recognized. In flowering plants, WGM is both ubiquitous and in many lineages cyclical, each round followed by substantial gene loss (fractionation). This process may be biased with respect to duplicated chromosomes, often with overexpression of genes in less fractionated relative to more fractionated regions. This bias is hypothesized to arise through downregulation of gene expression through silencing of local transposable elements (TEs). We assess differences in gene expression between duplicated regions of the paleopolyploid cotton genome and demonstrate that the rate of fractionation is negatively correlated with gene expression. We examine recent hypotheses regarding the source of fractionation bias and show that TE-mediated, positional downregulation is absent in the modern cotton genome, seemingly excluding this phenomenon as the primary driver of biased gene loss. Nevertheless, the paleo subgenomes of diploid cotton are still distinguishable with respect to TE content, targeting of 24-nt-small interfering RNAs and GC content, despite approximately 60 My of evolution. We propose that repeat content per se and differential recombination rates may drive biased fractionation following WGM. These data highlight the likely importance of ancient genomic fractionation biases in shaping modern crop genomes.

• http://mbe.oxfordjournals.org/cgi/content/short/32/4/1063?rss=1

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通过选择性剪接和NMD剪接因子调节是保守的王国之间尚未进化灵活

Ultraconserved elements, unusually long regions of perfect sequence identity, are found in genes encoding numerous RNA-binding proteins including arginine-serine rich (SR) splicing factors. Expression of these genes is regulated via alternative splicing of the ultraconserved regions to yield mRNAs that are degraded by nonsense-mediated mRNA decay (NMD), a process termed unproductive splicing (Lareau et al. 2007; Ni et al. 2007). As all human SR genes are affected by alternative splicing and NMD, one might expect this regulation to have originated in an early SR gene and persisted as duplications expanded the SR family. But in fact, unproductive splicing of most human SR genes arose independently (Lareau et al. 2007). This paradox led us to investigate the origin and proliferation of unproductive splicing in SR genes. We demonstrate that unproductive splicing of the splicing factor SRSF5 (SRp40) is conserved among all animals and even observed in fungi; this is a rare example of alternative splicing conserved between kingdoms, yet its effect is to trigger mRNA degradation. As the gene duplicated, the ancient unproductive splicing was lost in paralogs, and distinct unproductive splicing evolved rapidly and repeatedly to take its place. SR genes have consistently employed unproductive splicing, and while it is exceptionally conserved in some of these genes, turnover in specific events among paralogs shows flexible means to the same regulatory end.

• http://mbe.oxfordjournals.org/cgi/content/short/32/4/1072?rss=1

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汇总并确定疟疾寄生虫的出现的耐药决定因素的罕见变异联想测试序列

We explored the potential of pooled sequencing to swiftly and economically identify selective sweeps due to emerging artemisinin (ART) resistance in a South-East Asian malaria parasite population. ART resistance is defined by slow parasite clearance from the blood of ART-treated patients and mutations in the kelch gene (chr. 13) have been strongly implicated to play a role. We constructed triplicate pools of 70 slow-clearing (resistant) and 70 fast-clearing (sensitive) infections collected from the Thai–Myanmar border and sequenced these to high (~150-fold) read depth. Allele frequency estimates from pools showed almost perfect correlation (Lin’s concordance = 0.98) with allele frequencies at 93 single nucleotide polymorphisms measured directly from individual infections, giving us confidence in the accuracy of this approach. By mapping genome-wide divergence (F_ST) between pools of drug-resistant and drug-sensitive parasites, we identified two large (>150 kb) regions (on chrs. 13 and 14) and 17 smaller candidate genome regions. To identify individual genes within these genome regions, we resequenced an additional 38 parasite genomes (16 slow and 22 fast-clearing) and performed rare variant association tests. These confirmed kelch as a major molecular marker for ART resistance (P = 6.03 x 10^–6). This two-tier approach is powerful because pooled sequencing rapidly narrows down genome regions of interest, while targeted rare variant association testing within these regions can pinpoint the genetic basis of resistance. We show that our approach is robust to recurrent mutation and the generation of soft selective sweeps, which are predicted to be common in pathogen populations with large effective population sizes, and may confound more traditional gene mapping approaches.

• http://mbe.oxfordjournals.org/cgi/content/short/32/4/1080?rss=1

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在灵长类动物的基因数据集检测正选择物种表征的影响

Over evolutionary time, both host- and virus-encoded genes have been continually selected to modify their interactions with one another. This has resulted in the rapid evolution of the specific codons that govern the physical interactions between host and virus proteins. Virologists have discovered that these evolutionary signatures, acquired in nature, can provide a shortcut in the functional dissection of host–virus interactions in the laboratory. However, the use of evolution studies in this way is complicated by the fact that many nonhuman primate species are endangered, and biomaterials are often difficult to acquire. Here, we assess how the species representation in primate gene data sets affects the detection of positive natural selection. Our results demonstrate how targeted primate sequencing projects could greatly enhance research in immunology, virology, and beyond.

• http://mbe.oxfordjournals.org/cgi/content/short/32/4/1091?rss=1

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DN / DS和规模选择系数之间的关系

Numerous computational methods exist to assess the mode and strength of natural selection in protein-coding sequences, yet how distinct methods relate to one another remains largely unknown. Here, we elucidate the relationship between two widely used phylogenetic modeling frameworks: dN/dS models and mutation-selection (MutSel) models. We derive a mathematical relationship between dN/dS and scaled selection coefficients, the focal parameters of MutSel models, and use this relationship to gain deeper insight into the behaviors, limitations, and applicabilities of these two modeling frameworks. We prove that, if all synonymous changes are neutral, standard MutSel models correspond to $$dN/dS\le 1$$. However, if synonymous codons differ in fitness, dN/dS can take on arbitrarily high values even if all selection is purifying. Thus, the MutSel modeling framework cannot necessarily accommodate positive, diversifying selection, while dN/dS cannot distinguish between purifying selection on synonymous codons and positive selection on amino acids. We further propose a new benchmarking strategy of dN/dS inferences against MutSel simulations and demonstrate that the widely used Goldman–Yang-style dN/dS models yield substantially biased dN/dS estimates on realistic sequence data. In contrast, the less frequently used Muse–Gaut-style models display much less bias. Strikingly, the least-biased and most precise dN/dS estimates are never found in the models with the best fit to the data, measured through both AIC and BIC scores. Thus, selecting models based on goodness-of-fit criteria can yield poor parameter estimates if the models considered do not precisely correspond to the underlying mechanism that generated the data. In conclusion, establishing mathematical links among modeling frameworks represents a novel, powerful strategy to pinpoint previously unrecognized model limitations and strengths.

• http://mbe.oxfordjournals.org/cgi/content/short/32/4/1097?rss=1

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codabc：计算框架来coestimate重组，置换，和分子适应率近似计算

The estimation of substitution and recombination rates can provide important insights into the molecular evolution of protein-coding sequences. Here, we present a new computational framework, called "CodABC," to jointly estimate recombination, substitution and synonymous and nonsynonymous rates from coding data. CodABC uses approximate Bayesian computation with and without regression adjustment and implements a variety of codon models, intracodon recombination, and longitudinal sampling. CodABC can provide accurate joint parameter estimates from recombining coding sequences, often outperforming maximum-likelihood methods based on more approximate models. In addition, CodABC allows for the inclusion of several nuisance parameters such as those representing codon frequencies, transition matrices, heterogeneity across sites or invariable sites. CodABC is freely available from http://code.google.com/p/codabc/, includes a GUI, extensive documentation and ready-to-use examples, and can run in parallel on multicore machines.

• http://mbe.oxfordjournals.org/cgi/content/short/32/4/1109?rss=1

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疫苗的进化速率显示强烈影响延迟：水痘-带状疱疹病毒的流行病学意义

Varicella-zoster virus (VZV) causes chickenpox and shingles, and is found in human populations worldwide. The lack of temporal signal in the diversity of VZV makes substitution rate estimates unreliable, which is a barrier to understanding the context of its global spread. Here, we estimate rates of evolution by studying live attenuated vaccines, which evolved in 22 vaccinated patients for known periods of time, sometimes, but not always undergoing latency. We show that the attenuated virus evolves rapidly (~10^–6 substitutions/site/day), but that rates decrease dramatically when the virus undergoes latency. These data are best explained by a model in which viral populations evolve for around 13 days before becoming latent, but then undergo no replication during latency. This implies that rates of viral evolution will depend strongly on transmission patterns. Nevertheless, we show that implausibly long latency periods are required to date the most recent common ancestor of extant VZV to an "out-of-Africa" migration with humans, as has been previously suggested.

• http://mbe.oxfordjournals.org/cgi/content/short/32/4/1020?rss=1

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在果蝇中醛脱氢酶独立睾丸特异重复并行功能的变化

A large proportion of duplicates, originating from ubiquitously expressed genes, acquire testis-biased expression. Identifying the underlying cause of this observation requires determining whether the duplicates have altered functions relative to the parental genes. Typically, statistical methods are used to test for positive selection, signature of which in protein sequence of duplicates implies functional divergence. When assumptions are violated, however, such tests can lead to false inference of positive selection. More convincing evidence for naturally selected functional changes would be the occurrence of structural changes with similar functional consequences in independent duplicates of the same gene. We investigated two testis-specific duplicates of the broadly expressed enzyme gene Aldehyde dehydrogenase (Aldh) that arose in different Drosophila lineages. The duplicates show a typical pattern of accelerated amino acid substitutions relative to their broadly expressed paralogs, with statistical evidence for positive selection in both cases. Importantly, in both duplicates, width of the entrance to the substrate binding site, known a priori to influence substrate specificity, and otherwise conserved throughout the genus Drosophila, has been reduced, resulting in narrowing of the entrance. Protein structure modeling suggests that the reduction of the size of the enzyme’s substrate entry channel, which is likely to shift substrate specificity toward smaller aldehydes, is accounted for by the positively selected parallel substitutions in one duplicate but not the other. Evolution of the testis-specific duplicates was accompanied by reduction in expression of the ancestral Aldh in males, supporting the hypothesis that the duplicates may have helped resolve intralocus sexual conflict over Aldh function.

• http://mbe.oxfordjournals.org/cgi/content/short/32/4/1029?rss=1

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生命之树显示时钟般的形态和多样化

Genomic data are rapidly resolving the tree of living species calibrated to time, the timetree of life, which will provide a framework for research in diverse fields of science. Previous analyses of taxonomically restricted timetrees have found a decline in the rate of diversification in many groups of organisms, often attributed to ecological interactions among species. Here, we have synthesized a global timetree of life from 2,274 studies representing 50,632 species and examined the pattern and rate of diversification as well as the timing of speciation. We found that species diversity has been mostly expanding overall and in many smaller groups of species, and that the rate of diversification in eukaryotes has been mostly constant. We also identified, and avoided, potential biases that may have influenced previous analyses of diversification including low levels of taxon sampling, small clade size, and the inclusion of stem branches in clade analyses. We found consistency in time-to-speciation among plants and animals, ~2 My, as measured by intervals of crown and stem species times. Together, this clock-like change at different levels suggests that speciation and diversification are processes dominated by random events and that adaptive change is largely a separate process.

• http://mbe.oxfordjournals.org/cgi/content/short/32/4/835?rss=1

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遗传因素相关的集群的进化起源C4光合作用被子植物

The evolutionary accessibility of novel adaptations varies among lineages, depending in part on the genetic elements present in each group. However, the factors determining the evolutionary potential of closely related genes remain largely unknown. In plants, CO₂-concentrating mechanisms such as C₄ and crassulacean acid metabolism (CAM) photosynthesis have evolved numerous times in distantly related groups of species, and constitute excellent systems to study constraints and enablers of evolution. It has been previously shown for multiple proteins that grasses preferentially co-opted the same gene lineage for C₄ photosynthesis, when multiple copies were present. In this work, we use comparative transcriptomics to show that this bias also exists within Caryophyllales, a distantly related group with multiple C₄ origins. However, the bias is not the same as in grasses and, when all angiosperms are considered jointly, the number of distinct gene lineages co-opted is not smaller than that expected by chance. These results show that most gene lineages present in the common ancestor of monocots and eudicots produced gene descendants that were recruited into C₄ photosynthesis, but that C₄-suitability changed during the diversification of angiosperms. When selective pressures drove C₄ evolution, some copies were preferentially co-opted, probably because they already possessed C₄-like expression patterns. However, the identity of these C₄-suitable genes varies among clades of angiosperms, and C₄ phenotypes in distant angiosperm groups thus represent genuinely independent realizations, based on different genetic precursors.

• http://mbe.oxfordjournals.org/cgi/content/short/32/4/846?rss=1

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选型交配驱动连锁不平衡精子和卵子识别蛋白位点之间的海胆海胆紫石

Sperm and eggs have interacting proteins on their surfaces that influence their compatibility during fertilization. These proteins are often polymorphic within species, producing variation in gamete affinities. We first demonstrate the fitness consequences of various sperm bindin protein (Bindin) variants in the sea urchin Strongylocentrotus purpuratus, and assortative mating between males and females based on their sperm Bindin genotype. This empirical finding of assortative mating based on sperm Bindin genotype could arise by linkage disequilibrium (LD) between interacting sperm and egg recognition loci. We then examine sequence variation in eight exons of the sea urchin egg receptor for sperm Bindin (EBR1). We find little evidence of LD among the eight exons of EBR1, yet strong evidence for LD between sperm Bindin and EBR1 overall, and varying degrees of LD between sperm Bindin among the eight exons. We reject the alternate hypotheses of LD driven by shared evolutionary histories, population structure, or close physical linkage between these interacting loci on the genome. The most parsimonious explanation for this pattern of LD is that it represents selection driven by assortative mating based on interactions among these sperm and egg loci. These findings indicate the importance of ongoing sexual selection in the maintenance of protein polymorphisms and LD, and more generally highlight how LD can be used as an indication of current mate choice, as opposed to historic selection.

• http://mbe.oxfordjournals.org/cgi/content/short/32/4/859?rss=1

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在禽流感的珠蛋白基因家族和血红蛋白亚型表达的基因进化的变化成交量

The apparent stasis in the evolution of avian chromosomes suggests that birds may have experienced relatively low rates of gene gain and loss in multigene families. To investigate this possibility and to explore the phenotypic consequences of variation in gene copy number, we examined evolutionary changes in the families of genes that encode the α- and β-type subunits of hemoglobin (Hb), the tetrameric α₂β₂ protein responsible for blood-O₂ transport. A comparative genomic analysis of 52 bird species revealed that the size and membership composition of the α- and β-globin gene families have remained remarkably constant during approximately 100 My of avian evolution. Most interspecific variation in gene content is attributable to multiple independent inactivations of the α^D-globin gene, which encodes the α-chain subunit of a functionally distinct Hb isoform (HbD) that is expressed in both embryonic and definitive erythrocytes. Due to consistent differences in O₂-binding properties between HbD and the major adult-expressed Hb isoform, HbA (which incorporates products of the α^A-globin gene), recurrent losses of α^D-globin contribute to among-species variation in blood-O₂ affinity. Analysis of HbA/HbD expression levels in the red blood cells of 122 bird species revealed high variability among lineages and strong phylogenetic signal. In comparison with the homologous gene clusters in mammals, the low retention rate for lineage-specific gene duplicates in the avian globin gene clusters suggests that the developmental regulation of Hb synthesis in birds may be more highly conserved, with orthologous genes having similar stage-specific expression profiles and similar functional properties in disparate taxa.

• http://mbe.oxfordjournals.org/cgi/content/short/32/4/871?rss=1

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{α} 2,3-sialyltransferases的整体观（ST3Gal）分子和功能进化的后口动物谱系特异性损失的意义：

Sialyltransferases are responsible for the synthesis of a diverse range of sialoglycoconjugates predicted to be pivotal to deuterostomes’ evolution. In this work, we reconstructed the evolutionary history of the metazoan α2,3-sialyltransferases family (ST3Gal), a subset of sialyltransferases encompassing six subfamilies (ST3Gal I–ST3Gal VI) functionally characterized in mammals. Exploration of genomic and expressed sequence tag databases and search of conserved sialylmotifs led to the identification of a large data set of st3gal-related gene sequences. Molecular phylogeny and large scale sequence similarity network analysis identified four new vertebrate subfamilies called ST3Gal III-r, ST3Gal VII, ST3Gal VIII, and ST3Gal IX. To address the issue of the origin and evolutionary relationships of the st3gal-related genes, we performed comparative syntenic mapping of st3gal gene loci combined to ancestral genome reconstruction. The ten vertebrate ST3Gal subfamilies originated from genome duplication events at the base of vertebrates and are organized in three distinct and ancient groups of genes predating the early deuterostomes. Inferring st3gal gene family history identified also several lineage-specific gene losses, the significance of which was explored in a functional context. Toward this aim, spatiotemporal distribution of st3gal genes was analyzed in zebrafish and bovine tissues. In addition, molecular evolutionary analyses using specificity determining position and coevolved amino acid predictions led to the identification of amino acid residues with potential implication in functional divergence of vertebrate ST3Gal. We propose a detailed scenario of the evolutionary relationships of st3gal genes coupled to a conceptual framework of the evolution of ST3Gal functions.

• http://mbe.oxfordjournals.org/cgi/content/short/32/4/906?rss=1

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在交配的花药黑穗菌型染色体非重组区的退化

Dimorphic mating-type chromosomes in fungi are excellent models for understanding the genomic consequences of recombination suppression. Their suppressed recombination and reduced effective population size are expected to limit the efficacy of natural selection, leading to genomic degeneration. Our aim was to identify the sequences of the mating-type chromosomes (a₁ and a₂) of the anther-smut fungi and to investigate degeneration in their nonrecombining regions. We used the haploid a₁ Microbotryum lychnidis-dioicae reference genome sequence. The a₁ and a₂ mating-type chromosomes were both isolated electrophoretically and sequenced. Integration with restriction-digest optical maps identified regions of recombination and nonrecombination in the mating-type chromosomes. Genome sequence data were also obtained for 12 other Microbotryum species. We found strong evidence of degeneration across the genus in the nonrecombining regions of the mating-type chromosomes, with significantly higher rates of nonsynonymous substitution (dN/dS) than in nonmating-type chromosomes or in recombining regions of the mating-type chromosomes. The nonrecombining regions of the mating-type chromosomes also showed high transposable element content, weak gene expression, and gene losses. The levels of degeneration did not differ between the a₁ and a₂ mating-type chromosomes, consistent with the lack of homogametic/heterogametic asymmetry between them, and contrasting with X/Y or Z/W sex chromosomes.

• http://mbe.oxfordjournals.org/cgi/content/short/32/4/928?rss=1

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对二倍体和四倍体拟南芥arenosa减数分裂基因的选择

Meiotic chromosome segregation is critical for fertility across eukaryotes, and core meiotic processes are well conserved even between kingdoms. Nevertheless, recent work in animals has shown that at least some meiosis genes are highly diverse or strongly differentiated among populations. What drives this remains largely unknown. We previously showed that autotetraploid Arabidopsis arenosa evolved stable meiosis, likely through reduced crossover rates, and that associated with this there is strong evidence for selection in a subset of meiosis genes known to affect axis formation, synapsis, and crossover frequency. Here, we use genome-wide data to study the molecular evolution of 70 meiosis genes in a much wider sample of A. arenosa. We sample the polyploid lineage, a diploid lineage from the Carpathian Mountains, and a more distantly related diploid lineage from the adjacent, but biogeographically distinct Pannonian Basin. We find that not only did selection act on meiosis genes in the polyploid lineage but also independently on a smaller subset of meiosis genes in Pannonian diploids. Functionally related genes are targeted by selection in these distinct contexts, and in two cases, independent sweeps occurred in the same loci. The tetraploid lineage has sustained selection on more genes, has more amino acid changes in each, and these more often affect conserved or potentially functional sites. We hypothesize that Pannonian diploid and tetraploid A. arenosa experienced selection on structural proteins that mediate sister chromatid cohesion, the formation of meiotic chromosome axes, and synapsis, likely for different underlying reasons.

• http://mbe.oxfordjournals.org/cgi/content/short/32/4/944?rss=1

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深分叉等位基因对环境的转录反应的拟南芥转录因子驱动的全基因组差异AREB1

Gene regulatory variation is an important driver of the evolution of physiological and developmental responses to the environment. The abscisic acid (ABA) signaling pathway has long been studied as a key component of the cellular response to abiotic stresses in plants. We identify two haplotypes in an Arabidopsis thaliana transcription factor, AREB1, which plays a central role in ABA-mediated response to osmotic stress. These two haplotypes show the sequence signature of long-term maintenance of genetic diversity, suggesting a role for a diversifying selection process such as balancing selection. We find that the two haplotypes, distinguished by a large number of single nucleotide polymorphisms and the presence or absence of four small insertion/deletions in AREB1 intron 1 and exon 2, are at roughly equal frequencies in Arabidopsis, and show high linkage disequilibrium and deep sequence divergence. We use a transgenic approach, along with mRNA Sequencing-based assay of genome-wide expression levels, and find considerable functional divergence between alleles representing the two haplotype groups. Specifically, we find that, under benign soil–water conditions, transgenic lines containing different AREB1 alleles differ in the expression of a large number of genes associated with pathogen response. There are relatively modest gene expression differences between the two transgenic lines under restricted soil water content. Our finding of pathogen-related activity expands the known roles of AREB1 in A. thaliana and reveals the molecular basis of gene-by-environment interaction in a putatively adaptive plant regulatory protein.

• http://mbe.oxfordjournals.org/cgi/content/short/32/4/956?rss=1

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人类的长非编码RNA信使RNA折叠比大幅减少

Long noncoding RNAs (lncRNAs) do not code for proteins but function as RNAs. Because the functions of an RNA rely on either its sequence or secondary structure, lncRNAs should be folded at least as strongly as messenger RNAs (mRNAs), which serve as messengers for translation and are generally thought to lack secondary structure-dependent RNA-level functions. Contrary to this prediction, analysis of genome-wide experimental data of human RNA folding reveals that lncRNAs are substantially less folded than mRNAs even after the control of expression level and GC% (percentage of guanines and cytosines), although both lncRNAs and mRNAs are more strongly folded than expected by chance. In contrast to mRNAs, lncRNAs show neither the positive correlation between folding strength and expression level nor the negative correlation between folding strength and evolutionary rate. These and other results support that although RNA folding undoubtedly plays a role in RNA biology it is also important in translation and/or protein biology.

• http://mbe.oxfordjournals.org/cgi/content/short/32/4/970?rss=1

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信令伙伴的适应性进化

Proteins that interact coevolve their structures. When mutation disrupts the interaction, compensation by the partner occurs to restore interaction otherwise counterselection occurs. We show in this study how a destabilizing mutation in one protein is compensated by a stabilizing mutation in its protein partner and their coevolving path. The pathway in this case and likely a general principle of coevolution is that the compensatory change must tolerate both the original and derived structures with equivalence in function and activity. Evolution of the structure of signaling elements in a network is constrained by specific protein pair interactions, by requisite conformational changes, and by catalytic activity. The heterotrimeric G protein-coupled signaling is a paragon of this protein interaction/function complexity and our deep understanding of this pathway in diverse organisms lends itself to evolutionary study. Regulators of G protein Signaling (RGS) proteins accelerate the intrinsic GTP hydrolysis rate of the Gα subunit of the heterotrimeric G protein complex. An important RGS-contact site is a hydroxyl-bearing residue on the switch I region of Gα subunits in animals and most plants, such as Arabidopsis. The exception is the grasses (e.g., rice, maize, sugarcane, millets); these plants have Gα subunits that replaced the critical hydroxyl-bearing threonine with a destabilizing asparagine shown to disrupt interaction between Arabidopsis RGS protein (AtRGS1) and the grass Gα subunit. With one known exception (Setaria italica), grasses do not encode RGS genes. One parsimonious deduction is that the RGS gene was lost in the ancestor to the grasses and then recently acquired horizontally in the lineage S. italica from a nongrass monocot. Like all investigated grasses, S. italica has the Gα subunit with the destabilizing asparagine residue in the protein interface but, unlike other known grass genomes, still encodes an expressed RGS gene, SiRGS1. SiRGS1 accelerates GTP hydrolysis at similar concentration of both Gα subunits containing either the stabilizing (AtGPA1) or destabilizing (RGA1) interface residue. SiRGS1 does not use the hydroxyl-bearing residue on Gα to promote GAP activity and has a larger Gα-interface pocket fitting to the destabilizing Gα. These findings indicate that SiRGS1 adapted to a deleterious mutation on Gα using existing polymorphism in the RGS protein population.

• http://mbe.oxfordjournals.org/cgi/content/short/32/4/998?rss=1

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自适应进化是物种特异性免疫反应的预测

It has been proposed that positive selection may be associated with protein functional change. For example, human and macaque have different outcomes to HIV infection and it has been shown that residues under positive selection in the macaque TRIM5α receptor locate to the region known to influence species-specific response to HIV. In general, however, the relationship between sequence and function has proven difficult to fully elucidate, and it is the role of large-scale studies to help bridge this gap in our understanding by revealing major patterns in the data that correlate genotype with function or phenotype. In this study, we investigate the level of species-specific positive selection in innate immune genes from human and mouse. In total, we analyzed 456 innate immune genes using codon-based models of evolution, comparing human, mouse, and 19 other vertebrate species to identify putative species-specific positive selection. Then we used population genomic data from the recently completed Neanderthal genome project, the 1000 human genomes project, and the 17 laboratory mouse genomes project to determine whether the residues that were putatively positively selected are fixed or variable in these populations. We find evidence of species-specific positive selection on both the human and the mouse branches and we show that the classes of genes under positive selection cluster by function and by interaction. Data from this study provide us with targets to test the relationship between positive selection and protein function and ultimately to test the relationship between positive selection and discordant phenotypes.

• http://mbe.oxfordjournals.org/cgi/content/short/msv051v2?rss=1

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Solubis:优化你的蛋白质

Motivation: Protein aggregation is associated with a number of protein misfolding diseases and is a major concern for therapeutic proteins. Aggregation is caused by the presence of aggregation-prone regions (APRs) in the amino acid sequence of the protein. The lower the aggregation propensity of APRs and the better they are protected by native interactions within the folded structure of the protein, the more aggregation is prevented. Therefore, both the local thermodynamic stability of APRs in the native structure and their intrinsic aggregation propensity are a key parameter that needs to be optimized to prevent protein aggregation.

Results: The Solubis method presented here automates the process of carefully selecting point mutations that minimize the intrinsic aggregation propensity while improving local protein stability.

Availability and implementation: All information about the Solubis plugin is available at http://solubisyasara.switchlab.org/.

Contact: joost.schymkowitz@switch.vib-kuleuven.be or Frederic.Rousseau@switch.vib-kuleuven.be

Supplementary information: Supplementary data are available at Bioinformatics online.

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv162v2?rss=1

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ChIPseeker:R / Bioconductor包芯片峰值注释、比较和可视化

Summary: ChIPseeker is an R package for annotating ChIP-seq data analysis. It supports annotating ChIP peaks and provides functions to visualize ChIP peaks coverage over chromosomes and profiles of peaks binding to TSS regions. Comparison of ChIP peak profiles and annotation are also supported. Moreover, it supports evaluating significant overlap among ChIP-seq datasets. Currently, ChIPseeker contains 15 000 bed file information from GEO database. These datasets can be downloaded and compare with user’s own data to explore significant overlap datasets for inferring co-regulation or transcription factor complex for further investigation.

Availability and implementation: ChIPseeker is released under Artistic-2.0 License. The source code and documents are freely available through Bioconductor (http://www.bioconductor.org/pack ages/release/bioc/html/ChIPseeker.html).

Contact: guangchuangyu@gmail.com or tqyhe@jnu.edu.cn

Supplementary information: Supplementary data are available at Bioinformatics online.

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv145v2?rss=1

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miR2GO:比较小分子核糖核酸的功能分析

Summary: miR2GO is a web-based platform for comparative analyses of human miRNA functions. It includes two programs: miRmut2GO and miRpair2GO. miRmut2GO implements a knowledge-based method to assess the functional effects of genetic and somatic mutations in microRNA seed regions. The functional effects of a mutation are analysed by semantic comparison of enriched gene ontology (GO) annotations of the target gene sets for the wild-type and mutated alleles. miRpair2GO compares the functions of two different miRNAs based on the enriched functional annotations of their target gene sets.

Availability and implementation: The miR2GO web server is available at http://compbio.uthsc.edu/miR2GO.

Contact: ycui2@uthsc.edu

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv140v2?rss=1

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基因水平逻辑转换公司的代谢模型的应用和分析

Motivation: In recent years, genome-scale metabolic models (GEMs) have played important roles in areas like systems biology and bioinformatics. However, because of the complexity of gene– reaction associations, GEMs often have limitations in gene level analysis and related applications. Hence, the existing methods were mainly focused on applications and analysis of reactions and metabolites.

Results: Here, we propose a framework named logic transformation of model (LTM) that is able to simplify the gene–reaction associations and enables integration with other developed methods for gene level applications. We show that the transformed GEMs have increased reaction and metabolite number as well as degree of freedom in flux balance analysis, but the gene–reaction associations and the main features of flux distributions remain constant. In addition, we develop two methods, OptGeneKnock and FastGeneSL by combining LTM with previously developed reaction-based methods. We show that the FastGeneSL outperforms exhaustive search. Finally, we demonstrate the use of the developed methods in two different case studies. We could design fast genetic intervention strategies for targeted overproduction of biochemicals and identify double and triple synthetic lethal gene sets for inhibition of hepatocellular carcinoma tumor growth through the use of OptGeneKnock and FastGeneSL, respectively.

Availability and implementation: Source code implemented in MATLAB, RAVEN toolbox and COBRA toolbox, is public available at https://sourceforge.net/projects/logictransformationofmodel.

Contact: nielsenj@chalmers.se or qhua@ecust.edu.cn

Supplementary information: Supplementary data are available at Bioinformatics Online.

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv134v2?rss=1

[详细]

BMRF-Net:软件工具识别的蛋白质交互装袋子网的马尔可夫随机现场检测方法

Summary: Identification of protein interaction subnetworks is an important step to help us understand complex molecular mechanisms in cancer. In this paper, we develop a BMRF-Net package, implemented in Java and C++, to identify protein interaction subnetworks based on a bagging Markov random field (BMRF) framework. By integrating gene expression data and protein–protein interaction data, this software tool can be used to identify biologically meaningful subnetworks. A user friendly graphic user interface is developed as a Cytoscape plugin for the BMRF-Net software to deal with the input/output interface. The detailed structure of the identified networks can be visualized in Cytoscape conveniently. The BMRF-Net package has been applied to breast cancer data to identify significant subnetworks related to breast cancer recurrence.

Availability and implementation: The BMRF-Net package is available at http://sourceforge.net/projects/bmrfcjava/. The package is tested under Ubuntu 12.04 (64-bit), Java 7, glibc 2.15 and Cytoscape 3.1.0.

Contact: xuan@vt.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv137v2?rss=1

[详细]