Patterns Of Positive Selection Research Articles

Evolutionary Impacts of Pattern Recognition Receptor Genes on Carnivora Complex Habitat Stress Adaptation.

Many mammals develop specific immune responses owing to the changes in their ecological niche and diet that are essential for animal survival. However, pattern recognition receptors (PRRs) serve as the first line of defense in innate immunity and generate immune responses in the host. However, the evolutionary impacts on PRR genes in Carnivora are not well studied. Herein, we explored the evolution of 946 PRR gene sequences in 43 Carnivora species to elucidate the molecular mechanisms of carnivore adaptation to complex habitats. We found that the PRRs were relatively conserved, and different gene families showed different evolutionary patterns. PRRs were highly purified based on their overall roles in Carnivora species but interspersed with positive-selection patterns during evolution. Different niche types may have jointly driven the evolution of PRR genes. In particular, the selection pressure of toll-like receptor (TLR) 10 was relaxed in seven species with pseudogenes, which may have emerged during recent evolutionary events. We speculated that a "functional compensation" mechanism may exist for genes with overlapping functions in the TLR gene family. Additionally, TLR2, TLR4, NLRC5, and DECTIN1 were subject to positive selection in semi-aquatic species, and the adaptive evolution of these genes may have been related to the adaptation to semi-aquatic environments. In summary, our findings offer valuable insights into the molecular and functional evolution of PRR genes, which are important for immune adaptations in Carnivora.

Genome-wide identification and comparative evolutionary analysis of sorbitol metabolism pathway genes in four Rosaceae species and three model plants

In contrast to most land plant species, sorbitol, instead of sucrose, is the major photosynthetic product in many Rosaceae species. It has been well illustrated that three key functional genes encoding sorbitol-6-phosphate dehydrogenase (S6PDH), sorbitol dehydrogenase (SDH), and sorbitol transporter (SOT), are mainly responsible for the synthesis, degradation and transportation of sorbitol. In this study, the genome-wide identification of S6PDH, SDH and SOT genes was conducted in four Rosaceae species, peach, mei, apple and pear, and showed the sorbitol bio-pathway to be dominant (named sorbitol present group, SPG); another three related species, including tomato, poplar and Arabidopsis, showed a non-sorbitol bio-pathway (named sorbitol absent group, SAG). To understand the evolutionary differences of the three important gene families between SAG and SPG, their corresponding gene duplication, evolutionary rate, codon bias and positive selection patterns have been analyzed and compared. The sorbitol pathway genes in SPG were found to be expanded through dispersed and tandem gene duplications. Branch-specific model analyses revealed SDH and S6PDH clade A were under stronger purifying selection in SPG. A higher frequency of optimal codons was found in S6PDH and SDH than that of SOT in SPG, confirming the purifying selection effect on them. In addition, branch-site model analyses revealed SOT genes were under positive selection in SPG. Expression analyses showed diverse expression patterns of sorbitol-related genes. Overall, these findings provide new insights in the evolutionary characteristics for the three key sorbitol metabolism-related gene families in Rosaceae and other non-sorbitol dominant pathway species.

Distinct evolutionary trajectories of V1R clades across mouse species

BackgroundMany animals rely heavily on olfaction to navigate their environment. Among rodents, olfaction is crucial for a wide range of social behaviors. The vomeronasal olfactory system in particular plays an important role in mediating social communication, including the detection of pheromones and recognition signals. In this study we examine patterns of vomeronasal type-1 receptor (V1R) evolution in the house mouse and related species within the genus Mus. We report the extent of gene repertoire turnover and conservation among species and clades, as well as the prevalence of positive selection on gene sequences across the V1R tree. By exploring the evolution of these receptors, we provide insight into the functional roles of receptor subtypes as well as the dynamics of gene family evolution.ResultsWe generated transcriptomes from the vomeronasal organs of 5 Mus species, and produced high quality V1R repertoires for each species. We find that V1R clades in the house mouse and relatives exhibit distinct evolutionary trajectories. We identify putative species-specific gene expansions, including a large clade D expansion in the house mouse. While gene gains are abundant, we detect very few gene losses. We describe a novel V1R clade and highlight candidate receptors for future study. We find evidence for distinct evolutionary processes across different clades, from largescale turnover to highly conserved repertoires. Patterns of positive selection are similarly variable, as some clades exhibit abundant positive selection while others display high gene sequence conservation. Based on clade-level evolutionary patterns, we identify receptor families that are strong candidates for detecting social signals and predator cues. Our results reveal clades with receptors detecting female reproductive status are among the most conserved across species, suggesting an important role in V1R chemosensation.ConclusionAnalysis of clade-level evolution is critical for understanding species’ chemosensory adaptations. This study provides clear evidence that V1R clades are characterized by distinct evolutionary trajectories. As receptor evolution is shaped by ligand identity, these results provide a framework for examining the functional roles of receptors.

Spread of variants with gene N hot spot mutations in russian SARS-CoV-2 isolates

SARS-CoV-2 is a RNA coronavirus of the β-CoVs family responsible for the pandemic of the severe acute respiratory syndrome (COVID-19). It is hypothesized that the viral genome of the contemporary predominant founder clones is likely to be evolving in geographic-dependent manner. Thus, strains of different origin may be characterized by different mutation patterns. The study was aimed to perform the mutational and phylogenetic analysis of the Russian SARS-CoV-2 genomes at different time periods and in various regions, as well as to characterize the mutational profiles of isolates using the bioinformatics approaches. The mutation accumulation was compared in 86 SARS-CoV-2 whole-genome sequences from Russia and 220 from Europe and North America in order to reveal the characteristic gene variations, the possible positive selection patterns. Along with the known mutation variants in the structural proteins genes, typical for isolates of European origin, several additional mutations including the synonymous mutation in gene M (C26750T) characteristic for Russian isolates were revealed. Double mutation R203K and G204R in the nucleocapside gene which previously emerged in Europe began spreading and rapidly (within a month) became the dominant form in Russia. The results obtained indicate that the viral genome of most Russian isolates evolves with accumulation of new mutations associated with increased viral transmission. Data on the SARS-CoV-2 genome specific mutation patterns might be used for the detection of the virus, as well as for tracking and controlling of its spread.

Positive selection analysis highlights key positions in plant PP2A regulatory subunits

ABSTRACTA versatile hub for cellular control, the eukaryotic protein phosphatase 2A (PP2A) enzyme family is thought to achieve specificity through combinatorial complexity. Phylogenetic analysis has revealed that expansion of PP2A gene families resulted from whole genome duplications followed by non-random gene loss, and selection analysis suggests that retention of B56/PPP2R5 gene family members after genome duplication events was driven by functional diversification. Here we identify the sites at which positive selection is detected in the plant B56 gene family, and discuss the significance of selection at these positions in the context of PP2A holoenzyme structure. The pattern of positive selection observed in the B11 subclade is distinctive, and suggests selective pressure on interactions with substrates and the enzymatic core.

College quality and the positive selection hypothesis: The ‘second filter’ on family background in high-paid jobs

This paper investigates the heterogeneous returns to college quality across the wage distribution, using Norwegian administrative data. An ongoing debate in the literature is whether students who are most likely to attend a high-quality college benefit the most from college quality (the positive selection hypothesis) or whether students who are least likely to attend a high-quality college benefit the most (the negative selection hypothesis). The findings in this paper support the predictions in the positive selection hypothesis, especially at the top of the wage distribution. But the findings suggest that this pattern of positive selection is not caused by students self-selecting into colleges based on expected gain. Instead, the findings suggest that a second filter on family background exists. Students from privileged background are not only more likely to attend a high-quality college (the first filter), but are also more likely to convert their high-quality college education into success at the labor market (the second filter).

Correction: Patterns of Positive Selection of the Myogenic Regulatory Factor Gene Family in Vertebrates

Correction: Patterns of Positive Selection of the Myogenic Regulatory Factor Gene Family in Vertebrates

Patterns of positive selection in seven ant genomes.

The evolution of ants is marked by remarkable adaptations that allowed the development of very complex social systems. To identify how ant-specific adaptations are associated with patterns of molecular evolution, we searched for signs of positive selection on amino-acid changes in proteins. We identified 24 functional categories of genes which were enriched for positively selected genes in the ant lineage. We also reanalyzed genome-wide data sets in bees and flies with the same methodology to check whether positive selection was specific to ants or also present in other insects. Notably, genes implicated in immunity were enriched for positively selected genes in the three lineages, ruling out the hypothesis that the evolution of hygienic behaviors in social insects caused a major relaxation of selective pressure on immune genes. Our scan also indicated that genes implicated in neurogenesis and olfaction started to undergo increased positive selection before the evolution of sociality in Hymenoptera. Finally, the comparison between these three lineages allowed us to pinpoint molecular evolution patterns that were specific to the ant lineage. In particular, there was ant-specific recurrent positive selection on genes with mitochondrial functions, suggesting that mitochondrial activity was improved during the evolution of this lineage. This might have been an important step toward the evolution of extreme lifespan that is a hallmark of ants.

Geographic variation in allele frequency of the gamete recognition protein M7 lysin throughout a mosaic blue mussel hybrid zone

Divergence at gamete recognition loci is hypothesized to result in speciation in broadcast spawning invertebrates. Many gamete recognition loci evolve quickly and show patterns of positive selection, yet the advantage of divergence is rarely known. M7 lysin is a sperm protein in the Mytilus edulis species complex that shows evidence of adaptive evolution. This locus is polymorphic with two distinct clades within Mytilus galloprovincialis, one of which, the D clade, shows the strongest signal of positive selection. We tested whether the geographic patterns in allele frequency were consistent with the hypothesis that positive selection on D clade alleles (G D ) was due to reinforcement. Populations of M. edulis showed little evidence of introgression of G D alleles, but there was no consistent evidence of reproductive character displacement. The lack of consistent patterns expected of reinforcement suggests that another mechanism is likely responsible for the adaptive divergence of M7 lysin.

Identification of positive selection in disease response genes within members of the Poaceae

Millions of years of coevolution between plants and pathogens can leave footprints on their genomes and genes involved on this interaction are expected to show patterns of positive selection in which novel, beneficial alleles are rapidly fixed within the population. Using information about upregulated genes in maize during Colletotrichum graminicola infection and resources available in the Phytozome database, we looked for evidence of positive selection in the Poaceae lineage, acting on protein coding sequences related with plant defense. We found six genes with evidence of positive selection and another eight with sites showing episodic selection. Some of them have already been described as evolving under positive selection, but others are reported here for the first time including genes encoding isocitrate lyase, dehydrogenases, a multidrug transporter, a protein containing a putative leucine-rich repeat and other proteins with unknown functions. Mapping positively selected residues onto the predicted 3-D structure of proteins showed that most of them are located on the surface, where proteins are in contact with other molecules. We present here a set of Poaceae genes that are likely to be involved in plant defense mechanisms and have evidence of positive selection. These genes are excellent candidates for future functional validation.

Increased viral quasispecies evolution in HBeAg seroconverter patients treated with oral nucleoside therapy

Increased viral diversity and evolution appear to be a pre-HBeAg-seroconversion feature in spontaneous and interferon-treated seroconverters. The aim of this study was to examine the viral evolution pattern in nucleoside analogue related HBeAg-seroconversion. This was a case control study consisting of ten lamivudine-treated HBeAg-seroconverters and ten lamivudine-treated non-seroconverters as matching controls. All patients in this study were followed as long as 6 years after starting lamivudine, and cases had three serum time points before HBeAg-seroconversion while controls had three matching serum time points. Nested PCR, cloning and sequencing of HBV precore/core gene were performed. Sequences were aligned with Clustal X 2.0. Phylogenetic trees were constructed and viral diversity, evolutionary rates and patterns of positive selection were evaluated. After starting lamivudine treatment, HBV viral diversity increased in both seroconverters and non-seroconverters, but seroconverters showed a significantly higher level of viral diversity that persisted over time by 2.1-fold (p = 0.009). The increased viral diversity correlated with reduced HBV DNA levels (p <0.001). Lamivudine-treated seroconverters had significant reduced HBV DNA concurrent with increased viral diversity after starting treatment (p = 0.001, compared to non-seroconverters, and resembled those of interferon-seroconverters published previously). There was evidence of positive selection in seroconverters with significantly increased amino acid changes compared to non-seroconverters (p <0.001), occurring in recognized T-cell and B-cell epitopes. Lamivudine-treated HBeAg-seroconverters showed a higher viral diversity than non-seroconverters, and the pattern resembled that of interferon-treated seroconverters. The findings strengthen the evidence that increased viral diversity is strongly associated with HBeAg-seroconversion.

Pervasive and Ongoing Positive Selection in the Vomeronasal-1 Receptor (V1R) Repertoire of Mouse Lemurs

Chemosensory genes are frequently the target of positive selection and are often present in large gene families, but little is known about heterogeneity of selection in these cases and its relation to function. Here, we use the vomeronasal-1 receptor (V1R) repertoire of mouse lemurs (Microcebus spp.) as a model system to study patterns of selection of chemosensory genes at several different levels. Mouse lemurs are small nocturnal strepsirrhine primates and have a large (~200 loci) repertoire of V1R loci that are likely important for intraspecific pheromonal communication and interspecific interactions, for example, recognition of predator cues. We investigated signals and patterns of positive selection among the 105 identified full length V1R loci in the gray mouse lemur and within 7 V1R loci amplified across multiple mouse lemur species. Phylogenetic reconstructions of published sequences revealed at least nine monophyletic clusters of V1Rs in gray mouse lemurs that have diversified since the split between lemurs and lorisoid primates. A large majority of clusters evolved under significant positive selection. Similar results were found in V1Rs of closely related greater galagos. Comparison with function of related V1R clusters in mice suggested a potential relationship between receptor function and strength of selection. Interestingly, most codons identified as being under positive selection are located in the extracellular domains of the receptors and hence likely indicate the position of residues involved in ligand binding. Positive selection was also detected within five V1R loci (=71% of analyzed loci) sequenced from 6 to 10 mouse lemur species, indicating ongoing selection within the genus, which may be related to sexual selection and, potentially, speciation processes. Variation in strength of positive selection on V1Rs showed no simple relationship to cluster size. The diversity of V1R loci in mouse lemurs reflects their adaptive evolution and is most likely related to the fundamental relevance of olfactory communication and predator recognition in these primates. Overall, adaptive evolution is the predominant mode of evolution of V1R loci at all levels, and the substantial heterogeneity in the strength of selection may be related to receptor function.

The function and evolution of the restriction factor viperin in primates was not driven by lentiviruses

BackgroundViperin, also known as RSAD2, is an interferon-inducible protein that potently restricts a broad range of different viruses such as influenza, hepatitis C virus, human cytomegalovirus and West Nile virus. Viperin is thought to affect virus budding by modification of the lipid environment within the cell. Since HIV-1 and other retroviruses depend on lipid domains of the host cell for budding and infectivity, we investigated the possibility that Viperin also restricts human immunodeficiency virus and other retroviruses.ResultsLike other host restriction factors that have a broad antiviral range, we find that viperin has also been evolving under positive selection in primates. The pattern of positive selection is indicative of Viperin's escape from multiple viral antagonists over the course of primate evolution. Furthermore, we find that Viperin is interferon-induced in HIV primary target cells. We show that exogenous expression of Viperin restricts the LAI strain of HIV-1 at the stage of virus release from the cell. Nonetheless, the effect of Viperin restriction is highly strain-specific and does not affect most HIV-1 strains or other retroviruses tested. Moreover, knockdown of endogenous Viperin in a lymphocytic cell line did not significantly affect the spreading infection of HIV-1.ConclusionDespite positive selection having acted on Viperin throughout primate evolution, our findings indicate that Viperin is not a major restriction factor against HIV-1 and other retroviruses. Therefore, other viral lineages are likely responsible for the evolutionary signatures of positive selection in viperin among primates.

Accelerated Evolution of the Prdm9 Speciation Gene across Diverse Metazoan Taxa

The onset of prezygotic and postzygotic barriers to gene flow between populations is a hallmark of speciation. One of the earliest postzygotic isolating barriers to arise between incipient species is the sterility of the heterogametic sex in interspecies' hybrids. Four genes that underlie hybrid sterility have been identified in animals: Odysseus, JYalpha, and Overdrive in Drosophila and Prdm9 (Meisetz) in mice. Mouse Prdm9 encodes a protein with a KRAB motif, a histone methyltransferase domain and several zinc fingers. The difference of a single zinc finger distinguishes Prdm9 alleles that cause hybrid sterility from those that do not. We find that concerted evolution and positive selection have rapidly altered the number and sequence of Prdm9 zinc fingers across 13 rodent genomes. The patterns of positive selection in Prdm9 zinc fingers imply that rapid evolution has acted on the interface between the Prdm9 protein and the DNA sequences to which it binds. Similar patterns are apparent for Prdm9 zinc fingers for diverse metazoans, including primates. Indeed, allelic variation at the DNA–binding positions of human PRDM9 zinc fingers show significant association with decreased risk of infertility. Prdm9 thus plays a role in determining male sterility both between species (mouse) and within species (human). The recurrent episodes of positive selection acting on Prdm9 suggest that the DNA sequences to which it binds must also be evolving rapidly. Our findings do not identify the nature of the underlying DNA sequences, but argue against the proposed role of Prdm9 as an essential transcription factor in mouse meiosis. We propose a hypothetical model in which incompatibilities between Prdm9-binding specificity and satellite DNAs provide the molecular basis for Prdm9-mediated hybrid sterility. We suggest that Prdm9 should be investigated as a candidate gene in other instances of hybrid sterility in metazoans.

An excess of rare genetic variation in ABCE1 among Yorubans and African-American individuals with HIV-1

Signatures of natural selection occur throughout the human genome and can be detected at the sequence level. We have re-sequenced ABCE1, a host candidate gene essential for HIV-1 capsid assembly, in European- (n=23) and African-descent (Yoruban; n=24) reference populations for genetic variation discovery. We identified an excess of rare genetic variation in Yoruban samples, and the resulting Tajima's D was low (-2.27). The trend of excess rare variation persisted in flanking candidate genes ANAPC10 and OTUD4, suggesting that this pattern of positive selection can be detected across the 184.5 kb examined on chromosome 4. Owing to ABCE1's role in HIV-1 replication, we re-sequenced the candidate gene in three small cohorts of HIV-1-infected or resistant individuals. We were able to confirm the excess of rare genetic variation among HIV-1-positive African-American individuals (n=53; Tajima's D=-2.34). These results highlight the potential importance of ABCE1's role in infectious diseases such as HIV-1.

Accurate Prediction of the Functional Significance of Single Nucleotide Polymorphisms and Mutations in the ABCA1 Gene

The human genome contains an estimated 100,000 to 300,000 DNA variants that alter an amino acid in an encoded protein. However, our ability to predict which of these variants are functionally significant is limited. We used a bioinformatics approach to define the functional significance of genetic variation in the ABCA1 gene, a cholesterol transporter crucial for the metabolism of high density lipoprotein cholesterol. To predict the functional consequence of each coding single nucleotide polymorphism and mutation in this gene, we calculated a substitution position-specific evolutionary conservation score for each variant, which considers site-specific variation among evolutionarily related proteins. To test the bioinformatics predictions experimentally, we evaluated the biochemical consequence of these sequence variants by examining the ability of cell lines stably transfected with the ABCA1 alleles to elicit cholesterol efflux. Our bioinformatics approach correctly predicted the functional impact of greater than 94% of the naturally occurring variants we assessed. The bioinformatics predictions were significantly correlated with the degree of functional impairment of ABCA1 mutations (r 2 = 0.62, p = 0.0008). These results have allowed us to define the impact of genetic variation on ABCA1 function and to suggest that the in silico evolutionary approach we used may be a useful tool in general for predicting the effects of DNA variation on gene function. In addition, our data suggest that considering patterns of positive selection, along with patterns of negative selection such as evolutionary conservation, may improve our ability to predict the functional effects of amino acid variation.

Patterns of positive selection in the complete NBS-LRR gene family of Arabidopsis thaliana.

Plant disease resistance genes have been shown to be subject to positive selection, particularly in the leucine rich repeat (LRR) region that may determine resistance specificity. We performed a genome-wide analysis of positive selection in members of the nucleotide binding site (NBS)-LRR gene family of Arabidopsis thaliana. Analyses were possible for 103 of 163 NBS-LRR nucleotide sequences in the genome, and the analyses uncovered substantial evidence of positive selection. Sites under positive selection were detected and identified for 10 sequence groups representing 53 NBS-LRR sequences. Functionally characterized Arabidopsis resistance genes were in these 10 groups, but several groups with extensive evidence of positive selection contained no previously characterized resistance genes. Amino acid residues under positive selection were identified, and these residues were mapped onto protein secondary structure. Positively selected positions were disproportionately located in the LRR domain (P < 0.001), particularly a nine-amino acid beta-strand submotif that is likely to be solvent exposed. However, a substantial proportion (30%) of positively selected sites were located outside LRRs, suggesting that regions other than the LRR may function in determining resistance specificity. Because of the unusual sequence variability in the LRRs of this class of proteins, secondary-structure analysis identifies LRRs that are not identified by similarity analyses alone. LRRs also contain substantial indel variation, suggesting elasticity in LRR length could also influence resistance specificity.

Normal thymic selection, superantigen-induced deletion and Fas-mediated apoptosis of T cells in IL-2 receptor beta chain-deficient mice.

Mice lacking the IL-2 receptor beta chain (IL-2R beta) exhibit an autoimmune reaction characterized by generalized T cell activation, production of autoantibodies, myeloproliferation and severe anemia. T cells of IL-2R beta-/- mice were examined to elucidate the mechanism responsible for their abnormal activation and to determine how such abnormal activation might affect other cell lineages. Elevated levels of IgG, IgE and autoantibodies in IL-2R beta-/- mice were found to be associated with activated CD4+ T cells which secreted elevated levels of IL-4. Thymocytes in IL-2R beta-/- mice showed normal negative and positive selection patterns when analyzed in transgenic mice bearing a TCR specific for HY antigen, suggesting that neither IL-2 nor IL-15 is essential for thymic selection. Peripheral T cells in IL-2R beta-deficient mice underwent normal programmed cell death in response to staphylococcal enterotoxin B superantigen, in contrast to cells from mice deficient for either IL-2 or IL-2R alpha. Activated T cells in IL-2R beta-deficient mice expressed normal levels of Fas antigen and underwent normal apoptosis in response to induction with anti-Fas mAb. Thus, the accumulation of activated T cells in IL-2R beta-/- mice does not appear to be derived from abnormalities in either thymic selection or Fas-mediated apoptosis.