scholarly journals Molecular Evolution in Small Steps under Prevailing Negative Selection: A Nearly Universal Rule of Codon Substitution

2019 ◽  
Vol 11 (10) ◽  
pp. 2702-2712 ◽  
Author(s):  
Qingjian Chen ◽  
Ao Lan ◽  
Xu Shen ◽  
Chung-I Wu
Keyword(s):  
Molecular Evolution ◽  
Positive Selection ◽  
Negative Selection ◽  
Evolutionary Rate ◽  
Small Step ◽  
Step Size ◽  
Entire Genome ◽  
Codon Substitution ◽  
Almost All ◽  
Codon Evolution

Abstract The widely accepted view that evolution proceeds in small steps is based on two premises: 1) negative selection acts strongly against large differences and 2) positive selection favors small-step changes. The two premises are not biologically connected and should be evaluated separately. We now extend a previous approach to studying codon evolution in the entire genome. Codon substitution rate is a function of the physicochemical distance between amino acids (AAs), equated with the step size of evolution. Between nine pairs of closely related species of plants, invertebrates, and vertebrates, the evolutionary rate is strongly and negatively correlated with a set of AA distances (ΔU, scaled to [0, 1]). ΔU, a composite measure of evolutionary rates across diverse taxa, is influenced by almost all of the 48 physicochemical properties used here. The new analyses reveal a crucial trend hidden from previous studies: ΔU is strongly correlated with the evolutionary rate (R2 > 0.8) only when the genes are predominantly under negative selection. Because most genes in most taxa are strongly constrained by negative selection, ΔU has indeed appeared to be a nearly universal measure of codon evolution. In conclusion, molecular evolution at the codon level generally takes small steps due to the prevailing negative selection. Whether positive selection may, or may not, follow the small-step rule is addressed in a companion study.

scholarly journals Molecular evolution in small steps under prevailing negative selection – A nearly-universal rule of codon substitution

2019 ◽  
Author(s):  
Qingjian Chen ◽  
Ao Lan ◽  
Xu Shen ◽  
Chung-I Wu
Keyword(s):  
Positive Selection ◽  
Negative Selection ◽  
Evolutionary Rate ◽  
Chemical Properties ◽  
Small Step ◽  
Step Size ◽  
Entire Genome ◽  
Codon Substitution ◽  
Physico Chemical ◽  
Codon Evolution

AbstractThe widely accepted view that evolution proceeds in small steps is based on two premises: i) negative selection acts strongly against large differences (Kimura 1983); and ii) positive selection favors small-step changes (Fisher 1930). The two premises are not biologically connected and should be evaluated separately. We now extend the approach of Tang et al. (2004) to codon evolution for the entire genome. Codon substitution rate is a function of the physico-chemical distance between amino acids (AAs), equated with the step size of evolution. This step size depends on a large number of physico-chemical properties as 46 of the 48 properties examined affect the rate. Between 9 pairs of closely-related species of plants, invertebrates and vertebrates, the evolutionary rate is indeed strongly andnegativelycorrelated with the AA distance (ΔU, scaled to [0, 1]). While the analyses corroborate the published results that relied on partial genomes, there is an important difference: ΔUis strongly correlated with the evolutionary rate (R2> 0.8) only when the genes are under predominant negative selection. Nevertheless, since most genes in most taxa are strongly constrained by negative selection, ΔUwould appear to be a nearly-universal measure of codon evolution. In conclusion, the driving force of the small-step evolution at the codon level is negative selection. The unanswered question of whether positive selection may, or may not, follow the small-step rule will be addressed in a companion study (Chen, et al. 2019).

scholarly journals Molecular evolution in large steps - Codon substitutions under positive selection

2019 ◽  
Author(s):  
Qingjian Chen ◽  
Ziwen He ◽  
Ao Lan ◽  
Haijun Wen ◽  
Chung-I Wu
Keyword(s):  
Molecular Evolution ◽  
Positive Selection ◽  
Negative Selection ◽  
Chemical Properties ◽  
Molecular Models ◽  
Step Size ◽  
Biochemical Basis ◽  
Mk Test ◽  
Physico Chemical ◽  
Adaptive Signal

AbstractMolecular evolution is believed to proceed in small steps. The step size can be defined by a distance reflecting physico-chemical disparities between amino acid (AA) pairs that can be exchanged by single 1 bp mutations. We show that AA substitution rates are strongly and negatively correlated with this distance but only when positive selection is relatively weak. We use the McDonald and Kreitman (MK) test to separate the influences of positive and negative selection. While negative selection is indeed stronger on AA substitutions generating larger changes in chemical properties of amino acids, positive selection operates by different rules. For 65 of the 75 possible pairs, positive selection is comparable in strength regardless of AA distance. However, the 10 pairs under the strongest positive selection all exhibit large leaps in chemical properties. Five of the 10 pairs are shared between hominoids andDrosophila, thus hinting at a common but modest biochemical basis of adaptation across taxa. The hypothesis that adaptive changes often take large functional steps will need to be extensively tested. If validated, molecular models will need to better integrate positive and negative selection in the search for adaptive signal.

scholarly journals Molecular Evolution in Large Steps—Codon Substitutions under Positive Selection

2019 ◽  
Vol 36 (9) ◽  
pp. 1862-1873 ◽  
Author(s):  
Qingjian Chen ◽  
Ziwen He ◽  
Ao Lan ◽  
Xu Shen ◽  
Haijun Wen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Molecular Evolution ◽  
Positive Selection ◽  
Negative Selection ◽  
Chemical Properties ◽  
Molecular Models ◽  
Step Size ◽  
Biochemical Basis ◽  
Physico Chemical ◽  
Adaptive Signal

AbstractMolecular evolution is believed to proceed in small steps. The step size can be defined by a distance reflecting physico-chemical disparities between amino acid (AA) pairs that can be exchanged by single 1-bp mutations. We show that AA substitution rates are strongly and negatively correlated with this distance but only when positive selection is relatively weak. We use the McDonald and Kreitman test to separate the influences of positive and negative selection. While negative selection is indeed stronger on AA substitutions generating larger changes in chemical properties of AAs, positive selection operates by different rules. For 65 of the 75 possible pairs, positive selection is comparable in strength regardless of AA distance. However, the ten pairs under the strongest positive selection all exhibit large leaps in chemical properties. Five of the ten pairs are shared between Drosophila and Hominoids, thus hinting at a common but modest biochemical basis of adaptation across taxa. The hypothesis that adaptive changes often take large functional steps will need to be extensively tested. If validated, molecular models will need to better integrate positive and negative selection in the search for adaptive signal.

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 Pick Your Poison: Molecular Evolution of Venom Proteins in Asilidae (Insecta: Diptera)

2020 ◽  
Author(s):  
Chris M. Cohen ◽  
T. Jeffrey Cole ◽  
Michael S. Brewer
Keyword(s):  
Salivary Gland ◽  
Molecular Evolution ◽  
Positive Selection ◽  
Negative Selection ◽  
Gene Families ◽  
Whole Body ◽  
Robber Flies ◽  
First Time ◽  
Venom Proteins

AbstractRobber flies are an understudied family of venomous, predatory Diptera. With the recent characterization of venom from three asilid species, it is possible for the first time to study the molecular evolution of venom genes in this unique lineage. To accomplish this, a novel whole-body transcriptome of Eudioctria media was combined with 10 other publicly available asiloid thoracic or salivary gland transcriptomes to identify putative venom gene families and assess evidence of pervasive positive selection. A total of 348 gene families of sufficient size were analyzed, and 33 of these were predicted to contain venom genes. We recovered 151 families containing homologs to previously described venoms, and 40 of these were uniquely gained in Asilidae. Our gene family clustering suggests that many asilidin venom gene families are not natural groupings as originally delimited. Additionally, robber-fly venoms have relatively few sites under positive selection, consistent with the hypothesis that the venom of older lineages are dominated by negative selection acting to maintain toxic function.

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 Two decades of suspect evidence for adaptive molecular evolution - Negative selection confounding positive selection signals

2021 ◽  
Author(s):  
Qipian Chen ◽  
Hao Yang ◽  
Xiao Feng ◽  
Qingjian Chen ◽  
Suhua Shi ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Positive Selection ◽  
Dna Sequences ◽  
Negative Selection ◽  
Genomic Sequence ◽  
Sequence Evolution ◽  
Mk Test ◽  
Random Expectation ◽  
Two Stages ◽  
Rule Out

There is a large literature in the last two decades affirming adaptive DNA sequences evolution between species. The main lines of evidence are from i) the McDonald-Kreitman (MK) test, which compares divergence and polymorphism data, and ii) the PAML test, which analyzes multi-species divergence data. Here, we apply these two tests concurrently on the genomic data of Drosophila and Arabidopsis. To our surprise, the >100 genes identified by the two tests do not overlap beyond random expectation. Because the non-concordance could be due to low powers leading to high false-negatives, we merge every 20 - 30 genes into a "supergene". At the supergene level, the power of detection is large but the calls still do not overlap. We rule out methodological reasons for the non-concordance. In particular, extensive simulations fail to find scenarios whereby positive selection can only be detected by either MK or PAML, but not both. Since molecular evolution is governed by positive and negative selection concurrently, a fundamental assumption for estimating one (say, positive selection) is that the other is constant. However, in a broad survey of primates, birds, Drosophila and Arabidopsis, we found that negative selection rarely stays constant for long in evolution. As a consequence, the variation in negative selection is often mis-construed as signals of positive selection. In conclusion, MK, PAML or any method that examines genomic sequence evolution has to explicitly address the variation in negative selection before estimating positive selection. In a companion study, we propose a possible path forward in two stages – first, by mapping out the changes in negative selection and then using this map to estimate positive selection. For now, the large literature on positive selection between species has to await the re-assessment.

scholarly journals Pick Your Poison: Molecular Evolution of Venom Proteins in Asilidae (Insecta: Diptera)

Toxins ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 738
Author(s):  
Chris M. Cohen ◽  
T. Jeffrey Cole ◽  
Michael S. Brewer
Keyword(s):  
Salivary Gland ◽  
Molecular Evolution ◽  
Positive Selection ◽  
Negative Selection ◽  
Gene Families ◽  
Whole Body ◽  
Robber Flies ◽  
First Time ◽  
Venom Proteins

Robber flies are an understudied family of venomous, predatory Diptera. With the recent characterization of venom from three asilid species, it is possible, for the first time, to study the molecular evolution of venom genes in this unique lineage. To accomplish this, a novel whole-body transcriptome of Eudioctria media was combined with 10 other publicly available asiloid thoracic or salivary gland transcriptomes to identify putative venom gene families and assess evidence of pervasive positive selection. A total of 348 gene families of sufficient size were analyzed, and 33 of these were predicted to contain venom genes. We recovered 151 families containing homologs to previously described venom proteins, and 40 of these were uniquely gained in Asilidae. Our gene family clustering suggests that many asilidin venom gene families are not natural groupings, as delimited by previous authors, but instead form multiple discrete gene families. Additionally, robber fly venoms have relatively few sites under positive selection, consistent with the hypothesis that the venoms of older lineages are dominated by negative selection acting to maintain toxic function.

scholarly journals Molecular Evolution of Duplicated Amylase Gene Regions in Drosophila melanogaster: Evidence of Positive Selection in the Coding Regions and Selective Constraints in the cis-Regulatory Regions

Genetics ◽  
2001 ◽  
Vol 157 (2) ◽  
pp. 667-677
Author(s):  
Hitoshi Araki ◽  
Nobuyuki Inomata ◽  
Tsuneyuki Yamazaki
Keyword(s):  
Drosophila Melanogaster ◽  
Molecular Evolution ◽  
Positive Selection ◽  
Natural Populations ◽  
Sliding Window ◽  
Selective Constraint ◽  
Proximal Region ◽  
Coding Regions ◽  
Asian Populations ◽  
Flanking Region

Abstract In this study, we randomly sampled Drosophila melanogaster from Japanese and Kenyan natural populations. We sequenced duplicated (proximal and distal) Amy gene regions to test whether the patterns of polymorphism were consistent with neutral molecular evolution. Fst between the two geographically distant populations, estimated from Amy gene regions, was 0.084, smaller than reported values for other loci, comparing African and Asian populations. Furthermore, little genetic differentiation was found at a microsatellite locus (DROYANETSB) in these samples (Gst′=−0.018). The results of several tests (Tajima's, Fu and Li's, and Wall's tests) were not significantly different from neutrality. However, a significantly higher level of fixed replacement substitutions was detected by a modified McDonald and Kreitman test for both populations. This indicates that positive selection occurred during or immediately after the speciation of D. melanogaster. Sliding-window analysis showed that the proximal region 1, a part of the proximal 5′ flanking region, was conserved between D. melanogaster and its sibling species, D. simulans. An HKA test was significant when the proximal region 1 was compared with the 5′ flanking region of Alcohol dehydrogenase (Adh), indicating a severe selective constraint on the Amy proximal region 1. These results suggest that natural selection has played an important role in the molecular evolution of Amy gene regions in D. melanogaster.

scholarly journals Codon-Substitution Models for Heterogeneous Selection Pressure at Amino Acid Sites

Genetics ◽  
2000 ◽  
Vol 155 (1) ◽  
pp. 431-449 ◽  
Author(s):  
Ziheng Yang ◽  
Rasmus Nielsen ◽  
Nick Goldman ◽  
Anne-Mette Krabbe Pedersen
Keyword(s):  
Amino Acid ◽  
Positive Selection ◽  
Selective Pressure ◽  
Acid Sites ◽  
Data Sets ◽  
Protein Coding ◽  
Important Indicator ◽  
Diversifying Selection ◽  
Codon Substitution ◽  
Neutral Mutations

AbstractComparison of relative fixation rates of synonymous (silent) and nonsynonymous (amino acid-altering) mutations provides a means for understanding the mechanisms of molecular sequence evolution. The nonsynonymous/synonymous rate ratio (ω = dN/dS) is an important indicator of selective pressure at the protein level, with ω = 1 meaning neutral mutations, ω < 1 purifying selection, and ω > 1 diversifying positive selection. Amino acid sites in a protein are expected to be under different selective pressures and have different underlying ω ratios. We develop models that account for heterogeneous ω ratios among amino acid sites and apply them to phylogenetic analyses of protein-coding DNA sequences. These models are useful for testing for adaptive molecular evolution and identifying amino acid sites under diversifying selection. Ten data sets of genes from nuclear, mitochondrial, and viral genomes are analyzed to estimate the distributions of ω among sites. In all data sets analyzed, the selective pressure indicated by the ω ratio is found to be highly heterogeneous among sites. Previously unsuspected Darwinian selection is detected in several genes in which the average ω ratio across sites is <1, but in which some sites are clearly under diversifying selection with ω > 1. Genes undergoing positive selection include the β-globin gene from vertebrates, mitochondrial protein-coding genes from hominoids, the hemagglutinin (HA) gene from human influenza virus A, and HIV-1 env, vif, and pol genes. Tests for the presence of positively selected sites and their subsequent identification appear quite robust to the specific distributional form assumed for ω and can be achieved using any of several models we implement. However, we encountered difficulties in estimating the precise distribution of ω among sites from real data sets.

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