scholarly journals Evaluation of an Improved Branch-Site Likelihood Method for Detecting Positive Selection at the Molecular Level

2005 ◽  
Vol 22 (12) ◽  
pp. 2472-2479 ◽  
Author(s):  
J. Zhang
Keyword(s):  
Positive Selection ◽  
Molecular Level ◽  
Likelihood Method ◽  
Branch Site

scholarly journals On the interpretation of results returned by branch-site models

2015 ◽  
Author(s):  
Stephane Guindon
Keyword(s):  
Positive Selection ◽  
Negative Selection ◽  
Molecular Level ◽  
Site Model ◽  
Branch Site ◽  
Codon Evolution ◽  
Interpretation Of Results

In a recent study, Murrell et al. (2015) compared the performance of several branch-site models of codon evolution. Their interpretation of results published by Lu & Guindon (2014) suggests that the stochastic branch-site model implemented in the software fitmodel is anti-conservative altogether, i.e., positive selection is detected more often than expected when analyzing sequences evolving under a mixture of neutrality and negative selection. I argue here that this presentation of the performance of fitmodel is misleading and should not deter evolutionary biologists from using this approach in exploratory analyses of selection patterns at the molecular level.

scholarly journals On the interpretation of results returned by branch-site models

2015 ◽  
Author(s):  
Stephane Guindon
Keyword(s):  
Positive Selection ◽  
Negative Selection ◽  
Molecular Level ◽  
Site Model ◽  
Branch Site ◽  
Codon Evolution ◽  
Interpretation Of Results

In a recent study, Murrell et al. (2015) compared the performance of several branch-site models of codon evolution. Their interpretation of results published by Lu & Guindon (2014) suggests that the stochastic branch-site model implemented in the software fitmodel is anti-conservative altogether, i.e., positive selection is detected more often than expected when analyzing sequences evolving under a mixture of neutrality and negative selection. I argue here that this presentation of the performance of fitmodel is misleading and should not deter evolutionary biologists from using this approach in exploratory analyses of selection patterns at the molecular level.

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

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3145 ◽  
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 ◽  
Signatures Of Selection

BackgroundThe capacity of visually oriented species to perceive and respond to visual signal is integral to their evolutionary success. Giraffes are 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 many of them. The extent to which the giraffe’s unique visual capacity and its difference with okapi is reflected by changes in their vision genes is not understood.MethodsThe recent availability of giraffe and okapi genomes 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 tests of positive selection and clade models of selection divergence through comparing giraffe and okapi vision genes and orthologous sequences from other mammals.ResultsSignatures of selection were 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 inCRYAAandOPN1LW. Significant selection divergence was identified inSAGwhile positive selection was detected inLUMwhen okapi is compared with ruminants and other mammals. Sequence analysis ofOPN1LWshowed that at least one of the sites known to affect spectral sensitivity of the red pigment is uniquely divergent between giraffe and other ruminants.DiscussionBy taking a systemic approach to gene function in vision, the results provide the first molecular clues associated with giraffe and okapi vision adaptations. At least some of the genes that exhibit signature of selection may reflect adaptive response to differences in giraffe and okapi habitat. We hypothesize that requirement for long distance vision associated with predation and communication with conspecifics likely played an important role in the adaptive pressure on giraffe vision genes.

scholarly journals Positive Selection in Gene Regulatory Factors Suggests Adaptive Pleiotropic Changes During Human Evolution

2021 ◽  
Vol 12 ◽  
Author(s):  
Vladimir M. Jovanovic ◽  
Melanie Sarfert ◽  
Carlos S. Reyna-Blanco ◽  
Henrike Indrischek ◽  
Dulce I. Valdivia ◽  
...  
Keyword(s):  
Positive Selection ◽  
Human Evolution ◽  
Target Genes ◽  
Population Data ◽  
Great Ape ◽  
Human Lineage ◽  
Regulatory Factors ◽  
Site Model ◽  
Branch Site ◽  
Gene Regulatory

Gene regulatory factors (GRFs), such as transcription factors, co-factors and histone-modifying enzymes, play many important roles in modifying gene expression in biological processes. They have also been proposed to underlie speciation and adaptation. To investigate potential contributions of GRFs to primate evolution, we analyzed GRF genes in 27 publicly available primate genomes. Genes coding for zinc finger (ZNF) proteins, especially ZNFs with a Krüppel-associated box (KRAB) domain were the most abundant TFs in all genomes. Gene numbers per TF family differed between all species. To detect signs of positive selection in GRF genes we investigated more than 3,000 human GRFs with their more than 70,000 orthologs in 26 non-human primates. We implemented two independent tests for positive selection, the branch-site-model of the PAML suite and aBSREL of the HyPhy suite, focusing on the human and great ape branch. Our workflow included rigorous procedures to reduce the number of false positives: excluding distantly similar orthologs, manual corrections of alignments, and considering only genes and sites detected by both tests for positive selection. Furthermore, we verified the candidate sites for selection by investigating their variation within human and non-human great ape population data. In order to approximately assign a date to positively selected sites in the human lineage, we analyzed archaic human genomes. Our work revealed with high confidence five GRFs that have been positively selected on the human lineage and one GRF that has been positively selected on the great ape lineage. These GRFs are scattered on different chromosomes and have been previously linked to diverse functions. For some of them a role in speciation and/or adaptation can be proposed based on the expression pattern or association with human diseases, but it seems that they all contributed independently to human evolution. Four of the positively selected GRFs are KRAB-ZNF proteins, that induce changes in target genes co-expression and/or through arms race with transposable elements. Since each positively selected GRF contains several sites with evidence for positive selection, we suggest that these GRFs participated pleiotropically to phenotypic adaptations in humans.

scholarly journals A spatially aware likelihood test to detect sweeps from haplotype distributions

2021 ◽  
Author(s):  
Michael DeGiorgio ◽  
Zachary A Szpiech
Keyword(s):  
Positive Selection ◽  
Frequency Spectrum ◽  
Haplotype Frequency ◽  
Positive Control ◽  
Composite Likelihood ◽  
Likelihood Method ◽  
Human Populations ◽  
Adaptive Mutations ◽  
Two Parameters ◽  
User Friendly

The inference of positive selection in genomes is a problem of great interest in evolutionary genomics. By identifying putative regions of the genome that contain adaptive mutations, we are able to learn about the biology of organisms and their evolutionary history. Here we introduce a composite likelihood method that identifies recently completed or ongoing positive selection by searching for extreme distortions in the spatial distribution of the haplotype frequency spectrum relative to the genome-wide expectation taken as neutrality. Furthermore, the method simultaneously infers two parameters of the sweep: the number of sweeping haplotypes and the ``width'' of the sweep, which is related to the strength and timing of selection. We demonstrate that this method outperforms the leading haplotype-based selection statistics. Then, as a positive control, we apply it to two well-studied human populations from the 1000 Genomes Project and examine haplotype frequency spectrum patterns at the LCT and MHC loci. To facilitate use of this method, we have implemented it in user-friendly open source software.

scholarly journals Directional divergence of EP300 duplicates in teleosts and its implications

2020 ◽  
Author(s):  
Xianzong Wang ◽  
Junli Yan
Keyword(s):  
Positive Selection ◽  
Developmental Disorders ◽  
Genome Duplication ◽  
Model Organism ◽  
Consensus Sequences ◽  
Branch Site ◽  
Extant Species ◽  
Regulation Network ◽  
Flanking Regions ◽  
Gene Expression Levels

Abstract Background: EP300 is a conserved protein in vertebrates, which serves as a key mediator of cellular homeostasis. Mutations and dysregulation of EP300 give rise to severe human developmental disorders and malignancy. Danio rerio is a promising model organism to study EP300 related diseases and drugs; however, the effect of EP300 duplicates derived from teleost-specific whole genome duplication should not just be neglected. Results: In this study, we obtained EP300 protein sequences of representative teleosts, mammals and sauropsids, with which we inferred a highly supported maximum likelihood tree. We observed that EP300 duplicates (EP300a and EP300b) were wildly retained in teleosts and universally expressed in a variety of tissues. Consensus sequences of EP300a and EP300b had exactly the same distribution of conserved domains, suggesting that their functions should be still largely overlapped. We analyzed molecular evolution of EP300 duplicates in teleosts, using branch-site models, clade models and site models. The results showed that both duplicates were subject to strong positive selection; however, for an extant species, generally at most one copy was under positive selection. At clade level, there was evident positive correlation between evolutionary rates, number of positively selected sites and gene expression levels. In Ostariophysi, EP300a were under stronger positive selection than EP300b; in Neoteleostei, another species-rich teleost clade, the contrary was the case. We also modeled 3D structures of zf-TAZ domain and its flanking regions of EP300a and EP300b of D. rerio and Oryzias latipes and found that in either species the faster evolving copy had more short helixes. Conclusions: Collectively, the two copies of EP300 have undoubtedly experienced directional divergence in main teleost clades. The divergence of EP300 between teleosts and mammals should be greater than divergence between different teleost clades. Further studies are needed to clarify to what extent the EP300 involved regulation network has diverged between teleosts and mammals, which would also be helpful to explain the huge success of teleosts.

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.

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