scholarly journals Multinucleotide mutations cause false inferences of lineage-specific positive selection

2017 ◽  
Author(s):  
Aarti Venkat ◽  
Matthew W. Hahn ◽  
Joseph W. Thornton
Keyword(s):  
Positive Selection ◽  
Adaptive Evolution ◽  
Alternative Model ◽  
Systematic Bias ◽  
Nucleotide Substitutions ◽  
Branch Site ◽  
Genome Wide ◽  
Sequence Patterns ◽  
Site Test ◽  
Mutational Processes

ABSTRACTPhylogenetic tests of adaptive evolution, which infer positive selection from an excess of nonsynonymous changes, assume that nucleotide substitutions occur singly and independently. But recent research has shown that multiple errors at adjacent sites often occur in single events during DNA replication. These multinucleotide mutations (MNMs) are overwhelmingly likely to be nonsynonymous. We therefore evaluated whether phylogenetic tests of adaptive evolution, such as the widely used branch-site test, might misinterpret sequence patterns produced by MNMs as false support for positive selection. We explored two genome-wide datasets comprising thousands of coding alignments – one from mammals and one from flies – and found that codons with multiple differences (CMDs) account for virtually all the support for lineage-specific positive selection inferred by the branch-site test. Simulations under genome-wide, empirically derived conditions without positive selection show that realistic rates of MNMs cause a strong and systematic bias in the branch-site and related tests; the bias is sufficient to produce false positive inferences approximately as often as the branch-site test infers positive selection from the empirical data. Our analysis indicates that genes may often be inferred to be under positive selection simply because they stochastically accumulated one or a few MNMs. Because these tests do not reliably distinguish sequence patterns produced by authentic positive selection from those caused by neutral fixation of MNMs, many published inferences of adaptive evolution using these techniques may therefore be artifacts of model violation caused by unincorporated neutral mutational processes. We develop an alternative model that incorporates MNMs and may be helpful in reducing this bias.

A Phenotype–Genotype Codon Model for Detecting Adaptive Evolution

2019 ◽  
Vol 69 (4) ◽  
pp. 722-738 ◽  
Author(s):  
Christopher T Jones ◽  
Noor Youssef ◽  
Edward Susko ◽  
Joseph P Bielawski
Keyword(s):  
Positive Selection ◽  
Adaptive Evolution ◽  
Evolutionary History ◽  
Life History Trait ◽  
Molecular Adaptation ◽  
Simulation Studies ◽  
Site Model ◽  
Branch Site ◽  
A Site ◽  
Post Hoc

Abstract A central objective in biology is to link adaptive evolution in a gene to structural and/or functional phenotypic novelties. Yet most analytic methods make inferences mainly from either phenotypic data or genetic data alone. A small number of models have been developed to infer correlations between the rate of molecular evolution and changes in a discrete or continuous life history trait. But such correlations are not necessarily evidence of adaptation. Here, we present a novel approach called the phenotype–genotype branch-site model (PG-BSM) designed to detect evidence of adaptive codon evolution associated with discrete-state phenotype evolution. An episode of adaptation is inferred under standard codon substitution models when there is evidence of positive selection in the form of an elevation in the nonsynonymous-to-synonymous rate ratio $\omega$ to a value $\omega > 1$. As it is becoming increasingly clear that $\omega > 1$ can occur without adaptation, the PG-BSM was formulated to infer an instance of adaptive evolution without appealing to evidence of positive selection. The null model makes use of a covarion-like component to account for general heterotachy (i.e., random changes in the evolutionary rate at a site over time). The alternative model employs samples of the phenotypic evolutionary history to test for phenomenological patterns of heterotachy consistent with specific mechanisms of molecular adaptation. These include 1) a persistent increase/decrease in $\omega$ at a site following a change in phenotype (the pattern) consistent with an increase/decrease in the functional importance of the site (the mechanism); and 2) a transient increase in $\omega$ at a site along a branch over which the phenotype changed (the pattern) consistent with a change in the site’s optimal amino acid (the mechanism). Rejection of the null is followed by post hoc analyses to identify sites with strongest evidence for adaptation in association with changes in the phenotype as well as the most likely evolutionary history of the phenotype. Simulation studies based on a novel method for generating mechanistically realistic signatures of molecular adaptation show that the PG-BSM has good statistical properties. Analyses of real alignments show that site patterns identified post hoc are consistent with the specific mechanisms of adaptation included in the alternate model. Further simulation studies show that the covarion-like component of the PG-BSM plays a crucial role in mitigating recently discovered statistical pathologies associated with confounding by accounting for heterotachy-by-any-cause. [Adaptive evolution; branch-site model; confounding; mutation-selection; phenotype–genotype.]

scholarly journals Detection of pathways affected by positive selection in primate lineages ancestral to humans

2016 ◽  
Author(s):  
J.T. Daub ◽  
S. Moretti ◽  
I. I. Davidov ◽  
L. Excoffier ◽  
M. Robinson-Rechavi
Keyword(s):  
Positive Selection ◽  
Functional Enrichment ◽  
Gene Trees ◽  
Gene Set Enrichment ◽  
Protein Coding ◽  
Gene Set ◽  
Branch Site ◽  
Gene Sets ◽  
Site Test ◽  
Polygenic Selection

AbstractGene set enrichment approaches have been increasingly successful in finding signals of recent polygenic selection in the human genome. In this study, we aim at detecting biological pathways affected by positive selection in more ancient human evolutionary history. Focusing on four branches of the primate tree that lead to modern humans, we tested all available protein coding gene trees of the Primates clade for signals of adaptation in these branches, using the likelihood-based branch site test of positive selection. The results of these locus-specific tests were then used as input for a gene set enrichment test, where whole pathways are globally scored for a signal of positive selection, instead of focusing only on outlier “significant” genes. We identified signals of positive selection in several pathways that are mainly involved in immune response, sensory perception, metabolism, and energy production. These pathway-level results are highly significant, even though there is no functional enrichment when only focusing on top scoring genes. Interestingly, several gene sets are found significant at multiple levels in the phylogeny, but different genes are responsible for the selection signal in the different branches. This suggests that the same function has been optimized in different ways at different times in primate evolution.

scholarly journals A Genome-Wide Identification of Genes Undergoing Recombination and Positive Selection inNeisseria

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Dong Yu ◽  
Yuan Jin ◽  
Zhiqiu Yin ◽  
Hongguang Ren ◽  
Wei Zhou ◽  
...  
Keyword(s):  
Positive Selection ◽  
Adaptive Evolution ◽  
Molecular Mechanisms ◽  
Acid Sites ◽  
Gram Negative Bacteria ◽  
Orthologous Genes ◽  
Genome Wide ◽  
A Genome ◽  
History Of ◽  
Functional Analyses

Currently, there is particular interest in the molecular mechanisms of adaptive evolution in bacteria.Neisseriais a genus of gram negative bacteria, and there has recently been considerable focus on its two human pathogenic speciesN. meningitidisandN. gonorrhoeae. Until now, no genome-wide studies have attempted to scan for the genes related to adaptive evolution. For this reason, we selected 18Neisseriagenomes (14N. meningitidis, 3N. gonorrhoeaeand 1 commensalN. lactamics) to conduct a comparative genome analysis to obtain a comprehensive understanding of the roles of natural selection and homologous recombination throughout the history of adaptive evolution. Among the 1012 core orthologous genes, we identified 635 genes with recombination signals and 10 genes that showed significant evidence of positive selection. Further functional analyses revealed that no functional bias was found in the recombined genes. Positively selected genes are prone to DNA processing and iron uptake, which are essential for the fundamental life cycle. Overall, the results indicate that both recombination and positive selection play crucial roles in the adaptive evolution ofNeisseriagenomes. The positively selected genes and the corresponding amino acid sites provide us with valuable targets for further research into the detailed mechanisms of adaptive evolution inNeisseria.

scholarly journals Evolutionary analysis of vision genes identifies potential drivers of visual differences between giraffe and okapi

2016 ◽  
Author(s):  
Edson Ishengoma ◽  
Morris Agaba ◽  
Douglas R Cavener
Keyword(s):  
Positive Selection ◽  
Visual Signal ◽  
Evolutionary Analysis ◽  
Long Distance ◽  
Phenotypic Differences ◽  
Multiple Strategies ◽  
Branch Site ◽  
Signature Of Selection ◽  
Evolutionary Success ◽  
Site Test

Background. The capacity of species to respond and perceive visual signal is integral to their evolutionary success. Giraffe is closely related to okapi, but the two species have broad range of phenotypic differences including their visual capacities. Vision studies rank giraffe’s visual acuity higher than all other artiodactyls despite sharing similar vision ecological determinants with most of them. To what extent giraffe unique visual capacity and its difference with okapi is reflected by changes in their vision genes is not understood. Methods. The recent availability of giraffe and okapi genome provided opportunity to identify giraffe and okapi vision genes. Multiple strategies were employed to identify thirty-six candidate mammalian vision genes in giraffe and okapi genomes. Quantification of selection pressure was performed by a combination of branch-site test of positive selection and clade models of selection divergence through comparing giraffe and okapi vision genes and their corresponding orthologous sequences from other mammals obtained from public gene banks. Results. Signatures of selection was identified in key genes that could potentially underlie giraffe and okapi visual adaptations. Importantly, some genes that contribute to optical transparency of the eye and those that are critical in light signaling pathway were found to show signatures of adaptive evolution or selection divergence. Comparison between giraffe and other ruminants identifies significant selection divergence in CRYAA and OPN1LW in giraffe. Significant selection divergence was identified in SAG while positive selection was detected in LUM when okapi is compared with ruminants and other mammals. Sequence analysis of OPN1LW showed that at least one of the sites known to affect spectral sensitivity of the red pigment is uniquely divergent between giraffe and other ruminants. Discussion. By taking a systemic approach to gene function in vision, the results provide the first molecular clues associated with giraffe and okapi vision adaptation. At least some of the genes that exhibit signature of selection may reflect adaptive response to differences in giraffe and okapi habitat. Moreover, requirement for long distance vision associated with predation likely played an important role in the adaptive pressure on giraffe vision genes.

scholarly journals Adaptive evolution driving the young duplications in six Rosaceae species

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yan Zhong ◽  
Xiaohui Zhang ◽  
Qinglong Shi ◽  
Zong-Ming Cheng
Keyword(s):  
Positive Selection ◽  
Adaptive Evolution ◽  
Gene Families ◽  
Whole Genome Sequencing Data ◽  
Duplicate Genes ◽  
Plant Genomes ◽  
Rosaceae Species ◽  
Genome Wide ◽  
Evolutionary Features ◽  
Species Specific

Abstract Background In plant genomes, high proportions of duplicate copies reveals that gene duplications play an important role in the evolutionary processes of plant species. A series of gene families under positive selection after recent duplication events in plant genomes indicated the evolution of duplicates driven by adaptive evolution. However, the genome-wide evolutionary features of young duplicate genes among closely related species are rarely reported. Results In this study, we conducted a systematic survey of young duplicate genes at genome-wide levels among six Rosaceae species, whose whole-genome sequencing data were successively released in recent years. A total of 35,936 gene families were detected among the six species, in which 60.25% were generated by young duplications. The 21,650 young duplicate gene families could be divided into two expansion types based on their duplication patterns, species-specific and lineage-specific expansions. Our results showed the species-specific expansions advantaging over the lineage-specific expansions. In the two types of expansions, high-frequency duplicate domains exhibited functional preference in response to environmental stresses. Conclusions The functional preference of the young duplicate genes in both the expansion types showed that they were inclined to respond to abiotic or biotic stimuli. Moreover, young duplicate genes under positive selection in both species-specific and lineage-specific expansions suggested that they were generated to adapt to the environmental factors in Rosaceae species.

scholarly journals Evolutionary analysis of vision genes identifies potential drivers of visual differences between giraffe and okapi

2016 ◽  
Author(s):  
Edson Ishengoma ◽  
Morris Agaba ◽  
Douglas R Cavener
Keyword(s):  
Positive Selection ◽  
Visual Signal ◽  
Evolutionary Analysis ◽  
Long Distance ◽  
Phenotypic Differences ◽  
Multiple Strategies ◽  
Branch Site ◽  
Signature Of Selection ◽  
Evolutionary Success ◽  
Site Test

Background. The capacity of species to respond and perceive visual signal is integral to their evolutionary success. Giraffe is closely related to okapi, but the two species have broad range of phenotypic differences including their visual capacities. Vision studies rank giraffe’s visual acuity higher than all other artiodactyls despite sharing similar vision ecological determinants with most of them. To what extent giraffe unique visual capacity and its difference with okapi is reflected by changes in their vision genes is not understood. Methods. The recent availability of giraffe and okapi genome provided opportunity to identify giraffe and okapi vision genes. Multiple strategies were employed to identify thirty-six candidate mammalian vision genes in giraffe and okapi genomes. Quantification of selection pressure was performed by a combination of branch-site test of positive selection and clade models of selection divergence through comparing giraffe and okapi vision genes and their corresponding orthologous sequences from other mammals obtained from public gene banks. Results. Signatures of selection was identified in key genes that could potentially underlie giraffe and okapi visual adaptations. Importantly, some genes that contribute to optical transparency of the eye and those that are critical in light signaling pathway were found to show signatures of adaptive evolution or selection divergence. Comparison between giraffe and other ruminants identifies significant selection divergence in CRYAA and OPN1LW in giraffe. Significant selection divergence was identified in SAG while positive selection was detected in LUM when okapi is compared with ruminants and other mammals. Sequence analysis of OPN1LW showed that at least one of the sites known to affect spectral sensitivity of the red pigment is uniquely divergent between giraffe and other ruminants. Discussion. By taking a systemic approach to gene function in vision, the results provide the first molecular clues associated with giraffe and okapi vision adaptation. At least some of the genes that exhibit signature of selection may reflect adaptive response to differences in giraffe and okapi habitat. Moreover, requirement for long distance vision associated with predation likely played an important role in the adaptive pressure on giraffe vision genes.

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