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2.
Arindam Dutta Joydeep ChakrabortyTapan K. Dutta 《Biochemical and biophysical research communications》2013
Using different maximum-likelihood models of adaptive evolution, signatures of natural selective pressure, operating across the naphthalene family of dioxygenases, were examined. A lineage- and branch-site specific combined analysis revealed that purifying selection pressure dominated the evolutionary history of the enzyme family. Specifically, episodic positive Darwinian selection pressure, affecting only a few sites in a subset of lineages, was found to be responsible for the evolution of nitroarene dioxygenases (NArDO) from naphthalene dioxygenase (NDO). Site-specific analysis confirmed the absence of diversifying selection pressure at any particular site. Different sets of positively selected residues, obtained from branch-site specific analysis, were detected for the evolution of each NArDO. They were mainly located around the active site, the catalytic pocket and their adjacent regions, when mapped onto the 3D structure of the α-subunit of NDO. The present analysis enriches the current understanding of adaptive evolution and also broadens the scope for rational alteration of substrate specificity of enzyme by directed evolution. 相似文献
3.
Kosakovsky Pond SL Murrell B Fourment M Frost SD Delport W Scheffler K 《Molecular biology and evolution》2011,28(11):3033-3043
Adaptive evolution frequently occurs in episodic bursts, localized to a few sites in a gene, and to a small number of lineages in a phylogenetic tree. A popular class of "branch-site" evolutionary models provides a statistical framework to search for evidence of such episodic selection. For computational tractability, current branch-site models unrealistically assume that all branches in the tree can be partitioned a priori into two rigid classes--"foreground" branches that are allowed to undergo diversifying selective bursts and "background" branches that are negatively selected or neutral. We demonstrate that this assumption leads to unacceptably high rates of false positives or false negatives when the evolutionary process along background branches strongly deviates from modeling assumptions. To address this problem, we extend Felsenstein's pruning algorithm to allow efficient likelihood computations for models in which variation over branches (and not just sites) is described in the random effects likelihood framework. This enables us to model the process at every branch-site combination as a mixture of three Markov substitution models--our model treats the selective class of every branch at a particular site as an unobserved state that is chosen independently of that at any other branch. When benchmarked on a previously published set of simulated sequences, our method consistently matched or outperformed existing branch-site tests in terms of power and error rates. Using three empirical data sets, previously analyzed for episodic selection, we discuss how modeling assumptions can influence inference in practical situations. 相似文献
4.
B Murrell JO Wertheim S Moola T Weighill K Scheffler SL Kosakovsky Pond 《PLoS genetics》2012,8(7):e1002764
The imprint of natural selection on protein coding genes is often difficult to identify because selection is frequently transient or episodic, i.e. it affects only a subset of lineages. Existing computational techniques, which are designed to identify sites subject to pervasive selection, may fail to recognize sites where selection is episodic: a large proportion of positively selected sites. We present a mixed effects model of evolution (MEME) that is capable of identifying instances of both episodic and pervasive positive selection at the level of an individual site. Using empirical and simulated data, we demonstrate the superior performance of MEME over older models under a broad range of scenarios. We find that episodic selection is widespread and conclude that the number of sites experiencing positive selection may have been vastly underestimated. 相似文献
5.
Challenges of detecting directional selection after a bottleneck: lessons from Sorghum bicolor 总被引:2,自引:0,他引:2
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Multilocus surveys of sequence variation can be used to identify targets of directional selection, which are expected to have reduced levels of variation. Following a population bottleneck, the signal of directional selection may be hard to detect because many loci may have low variation by chance and the frequency spectrum of variation may be perturbed in ways that resemble the effects of selection. Cultivated Sorghum bicolor contains a subset of the genetic diversity found in its wild ancestor(s) due to the combined effects of a domestication bottleneck and human selection on traits associated with agriculture. As a framework for distinguishing between the effects of demography and selection, we sequenced 204 loci in a diverse panel of 17 cultivated S. bicolor accessions. Genomewide patterns of diversity depart strongly from equilibrium expectations with regard to the variance of the number of segregating sites, the site frequency spectrum, and haplotype configuration. Furthermore, gene genealogies of most loci with an excess of low frequency variants and/or an excess of segregating sites do not show the characteristic signatures of directional and diversifying selection, respectively. A simple bottleneck model provides an improved but inadequate fit to the data, suggesting the action of other population-level factors, such as population structure and migration. Despite a known history of recent selection, we find little evidence for directional selection, likely due to low statistical power and lack of an appropriate null model. 相似文献
6.
Miller SR 《Molecular ecology》2003,12(5):1237-1246
Determining the molecular basis of enzyme adaptation is central to understanding the evolution of environmental tolerance but is complicated by the fact that not all amino acid differences between ecologically divergent taxa are adaptive. Analysing patterns of nucleotide sequence evolution can potentially guide the investigation of protein adaptation by identifying candidate codon sites on which diversifying selection has been operating. Here, I test whether there is evidence for molecular adaptation of the carbon fixation gene rbcL for a clade of hot spring cyanobacteria in the genus Synechococcus that has diverged in thermotolerance. Amino acid replacements during Synechococcus radiation have resulted in an increase in the number of hydrophobic residues in the RbcLs of more thermotolerant strains. A similar increase in hydrophobicity has been observed for many thermostable proteins. Maximum likelihood models which allow for heterogeneity among codon sites in the ratio of nonsynonymous to synonymous nucleotide substitutions estimated a class of amino acid sites as a target of positive selection. Depending on the model, a single amino acid site that interacts with a flexible element involved in the opening and closing of the active site was estimated with either low or moderate support to be a member of this class. Site-directed mutagenesis approaches are being explored in order to directly test its adaptive significance. 相似文献
7.
Codon-substitution models for heterogeneous selection pressure at amino acid sites 总被引:77,自引:0,他引:77
Comparison 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 (omega = d(N)d(S)) is an important indicator of selective pressure at the protein level, with omega = 1 meaning neutral mutations, omega < 1 purifying selection, and omega > 1 diversifying positive selection. Amino acid sites in a protein are expected to be under different selective pressures and have different underlying omega ratios. We develop models that account for heterogeneous omega 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 omega among sites. In all data sets analyzed, the selective pressure indicated by the omega ratio is found to be highly heterogeneous among sites. Previously unsuspected Darwinian selection is detected in several genes in which the average omega ratio across sites is <1, but in which some sites are clearly under diversifying selection with omega > 1. Genes undergoing positive selection include the beta-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 omega and can be achieved using any of several models we implement. However, we encountered difficulties in estimating the precise distribution of omega among sites from real data sets. 相似文献
8.
Single likelihood ancestor counting (SLAC), fixed effects likelihood (FEL), and several random effects likelihood (REL) methods
were utilized to identify positively and negatively selected sites in sexually induced gene 1 (Sig1) of four different Thalassiosira species. The SLAC analysis did not find any sites affected by positive selection but suggested 13 sites influenced by negative
selection. The SLAC approach may be too conservative because of low sequence divergence. The FEL and REL analyses revealed
over 60 negatively selected sites and two positively selected sites that were unique to each method. The REL method may not
be able to reliably identify individual sites under selection when applied to short sequences with low divergence. Instead,
we proposed a new alignment-wide test for adaptive evolution based on codon models with variation in synonymous and nonsynonymous
substitution rates among sites and found evidence for diversifying evolution without relying on site-by-site testing. The
performance of the FEL and REL approaches was evaluated by subjecting the tests to a type I error rate simulation analysis,
using the specific characteristics of the Sig1 data set. Simulation results indicated that the FEL test had reasonable Type
I errors, while REL might have been too liberal, suggesting that the two positively selected sites identified by FEL (codons
94 and 174) are not likely to be false positives. The evolution of these codon sites, one of which is located in functional
domain II, appears to be associated with divergence among the three major Thalassiosira lineages.
Electronic Supplementary Material Electronic Supplementary material is available for this article at
and accessible for authorised users.
[Reviewing Editor: Dr. Martin Kreitman] 相似文献
9.
Johannesson H Vidal P Guarro J Herr RA Cole GT Taylor JW 《Molecular biology and evolution》2004,21(6):1134-1145
In this study, we investigate the possibility of selection acting on the proline-rich antigen (PRA) gene in natural populations of the two human pathogens, Coccidioides immitis and Coccidioides posadasii, and three of their close relatives, Chrysosporium lucknowense, Chrysosporium queenslandicum, and Uncinocarpus reesii. We addressed the following questions: Is diversifying selection acting on PRA in the pathogenic species as a result of avoidance of the host's immune system, and has adaptation to a pathogenic life style lead to positive directional selection and increased rate of evolution in PRA between the species? For these purposes, we amplified and sequenced from 40 individuals belonging to the five species, the entire coding region of the PRA gene, as well as partial sequences from the coding region of each of the three housekeeping genes glyderaldehyde-3-phosphate dehydrogenase, glutamine synthetase A, and hexokinase A. We used likelihood-based methods to compare models of different types of selective pressure among codons to analyze the mode of evolution of the genes and found that the PRA gene evolves under positive selection, but the investigated parts of the housekeeping genes evolve primarily under purifying selection. We found a very low level of intraspecific variability and no evidence of diversifying selection, suggesting that the increased rate of evolution in the PRA gene is not a result of avoidance of the host's immune system. Neither did likelihood-based analyses suggest that selection was stronger on the branch separating pathogenic and nonpathogenic species. Instead, we suggest that positive selection act on PRA as a consequence of spore cell-wall morphogenesis unique to each species. 相似文献
10.
Estimating diversifying selection and functional constraint in the presence of recombination
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Models of molecular evolution that incorporate the ratio of nonsynonymous to synonymous polymorphism (dN/dS ratio) as a parameter can be used to identify sites that are under diversifying selection or functional constraint in a sample of gene sequences. However, when there has been recombination in the evolutionary history of the sequences, reconstructing a single phylogenetic tree is not appropriate, and inference based on a single tree can give misleading results. In the presence of high levels of recombination, the identification of sites experiencing diversifying selection can suffer from a false-positive rate as high as 90%. We present a model that uses a population genetics approximation to the coalescent with recombination and use reversible-jump MCMC to perform Bayesian inference on both the dN/dS ratio and the recombination rate, allowing each to vary along the sequence. We demonstrate that the method has the power to detect variation in the dN/dS ratio and the recombination rate and does not suffer from a high false-positive rate. We use the method to analyze the porB gene of Neisseria meningitidis and verify the inferences using prior sensitivity analysis and model criticism techniques. 相似文献
11.
We present the statistical analysis of diversifying selective pressures on the hepatitis D antigen gene (HDAg). Thirty-three distinct HDAg sequences from subtypes I, II, and III were tested for positive selection using maximum likelihood methods based on models of codon substitution that allow variable selective pressures across sites. Such methods have been shown to be sufficiently accurate and successful in detecting positive selection in a variety of viral and nonviral protein-coding genes. About 11% of codon sites in HDAg were estimated to be under diversifying selection. Remarkably, most of the residues predicted to evolve under positive selection were located in the immunogenic domain and the N-terminus region with reported antigenic activity. These sites are potential targets of the hosts immune response. Identification of residues mutating to escape immune recognition may help to distinguish the most virulent strains and aid vaccine design. Possible interplay between positive selection and recombination on the gene is discussed but no significant evidence for recombination was found.This article contains online supplementary material.Reviewing Editor: Dr. Nicolas Galtier 相似文献
12.
A diverse range of organisms utilize neurotoxins that target specific ion channels and modulate their activity. Typically, toxins are clustered into several multigene families, providing an organism with the upper hand in the never-ending predator-prey arms race. Several gene families, including those encoding certain neurotoxins, have been subject to diversifying selection forces, resulting in rapid gene evolution. Here we sought a spatial pattern in the distribution of both diversifying and purifying selection forces common to neurotoxin gene families. Utilizing the mechanistic empirical combination model, we analyzed various toxin families from different phyla affecting various receptors and relying on diverse modes of action. Through this approach, we were able to detect clear correlations between the pharmacological surface of a toxin and rapidly evolving domains, rich in positively selected residues. On the other hand, patches of negatively selected residues were restricted to the nontoxic face of the molecule and most likely help in stabilizing the tertiary structure of the toxin. We thus propose a mutual evolutionary strategy of venomous animals in which adaptive molecular evolution is directed toward the toxin active surface. Furthermore, we propose that the binding domains of unstudied toxins could be readily predicted using evolutionary considerations. 相似文献
13.
Maximum-likelihood analysis of molecular adaptation in abalone sperm lysin reveals variable selective pressures among lineages and sites 总被引:16,自引:0,他引:16
Maximum-likelihood models of codon substitution were used to analyze sperm lysin genes of 25 abalone (HALIOTIS:) species to identify lineages and amino acid sites under diversifying selection. The models used the nonsynonymous/synonymous rate ratio (omega = d(N)/d(S)) as an indicator of selective pressure and allowed the ratio to vary among lineages or sites. Likelihood ratio tests suggested significant variation in selective pressure among lineages. The variable selective pressure provided an explanation for the previous observation that the omega ratio is >1 in comparisons of closely related species and <1 in comparisons of distantly related species. Computer simulations demonstrated that saturation of nonsynonymous substitutions and constraint on lysin structure were unlikely to account for the observed pattern. Lineages linking closely related sympatric species appeared to be under diversifying selection, while lineages separating distantly related species from different geographic locations were associated with low evolutionary rates. The selective pressure indicated by the omega ratio was found to vary greatly among amino acid sites in lysin. Sites under potential diversifying selection were identified. Ancestral lysins were inferred to trace the route of evolution at individual sites and to provide lysin sequences for future laboratory studies. 相似文献
14.
Accuracy and power of the likelihood ratio test in detecting adaptive molecular evolution 总被引:4,自引:0,他引:4
The selective pressure at the protein level is usually measured by the nonsynonymous/synonymous rate ratio (omega = dN/dS), with omega < 1, omega = 1, and omega > 1 indicating purifying (or negative) selection, neutral evolution, and diversifying (or positive) selection, respectively. The omega ratio is commonly calculated as an average over sites. As every functional protein has some amino acid sites under selective constraints, averaging rates across sites leads to low power to detect positive selection. Recently developed models of codon substitution allow the omega ratio to vary among sites and appear to be powerful in detecting positive selection in empirical data analysis. In this study, we used computer simulation to investigate the accuracy and power of the likelihood ratio test (LRT) in detecting positive selection at amino acid sites. The test compares two nested models: one that allows for sites under positive selection (with omega > 1), and another that does not, with the chi2 distribution used for significance testing. We found that use of the chi(2) distribution makes the test conservative, especially when the data contain very short and highly similar sequences. Nevertheless, the LRT is powerful. Although the power can be low with only 5 or 6 sequences in the data, it was nearly 100% in data sets of 17 sequences. Sequence length, sequence divergence, and the strength of positive selection also were found to affect the power of the LRT. The exact distribution assumed for the omega ratio over sites was found not to affect the effectiveness of the LRT. 相似文献
15.
Codon-substitution models to detect adaptive evolution that account for heterogeneous selective pressures among site classes. 总被引:8,自引:0,他引:8
The nonsynonymous to synonymous substitution rate ratio (omega = d(N)/d(S)) provides a sensitive measure of selective pressure at the protein level, with omega values <1, =1, and >1 indicating purifying selection, neutral evolution, and diversifying selection, respectively. Maximum likelihood models of codon substitution developed recently account for variable selective pressures among amino acid sites by employing a statistical distribution for the omega ratio among sites. Those models, called random-sites models, are suitable when we do not know a priori which sites are under what kind of selective pressure. Sometimes prior information (such as the tertiary structure of the protein) might be available to partition sites in the protein into different classes, which are expected to be under different selective pressures. It is then sensible to use such information in the model. In this paper, we implement maximum likelihood models for prepartitioned data sets, which account for the heterogeneity among site partitions by using different omega parameters for the partitions. The models, referred to as fixed-sites models, are also useful for combined analysis of multiple genes from the same set of species. We apply the models to data sets of the major histocompatibility complex (MHC) class I alleles from human populations and of the abalone sperm lysin genes. Structural information is used to partition sites in MHC into two classes: those in the antigen recognition site (ARS) and those outside. Positive selection is detected in the ARS by the fixed-sites models. Similarly, sites in lysin are classified into the buried and solvent-exposed classes according to the tertiary structure, and positive selection was detected at the solvent-exposed sites. The random-sites models identified a number of sites under positive selection in each data set, confirming and elaborating the results of the fixed-sites models. The analysis demonstrates the utility of the fixed-sites models, as well as the power of previous random-sites models, which do not use the prior information to partition sites. 相似文献
16.
Bergmann PJ Meyers JJ Irschick DJ 《Evolution; international journal of organic evolution》2009,63(1):215-227
Although studied in many taxa, directional macroevolution remains difficult to detect and quantify. We present an approach for detecting directional evolution in subclades of species when relatively few species are sampled, and apply it to studying the evolution of stockiness in Phrynosomatine lizards. Our approach is more sensitive to detecting the tempo of directional evolution than other available approaches. We use ancestral reconstruction and phylogenetic mapping of morphology to characterize the direction and magnitude of trait evolution. We demonstrate a directional trend toward stockiness in horned lizards, but not their sister groups, finding that stockier species tend to have relatively short and wide bodies, and relatively short heads, tails, and limbs. Ornstein–Uhlenbeck models show that the directional trend in horned lizards is due to a shift in selective regime and stabilizing selection as opposed to directional selection. Bayesian evolutionary correlation analyses indicate that stockier species run more slowly and eat a larger proportion of ants. Furthermore, species with larger horns tend to be slower and more ant-specialized. Directional evolution toward a stocky body shape has evolved in conjunction with changes in a suite of traits, representing a complex example of directional macroevolution. 相似文献
17.
Viruses impose diverse and dynamic challenges on host defenses. Diversifying selection of codons and gene copy number variation are two hallmarks of genetic innovation in antiviral genes engaged in host-virus genetic conflicts. The myxovirus resistance (Mx) genes encode interferon-inducible GTPases that constitute a major arm of the cell-autonomous defense against viral infection. Unlike the broad antiviral activity of MxA, primate MxB was recently shown to specifically inhibit lentiviruses including HIV-1. We carried out detailed evolutionary analyses to investigate whether genetic conflict with lentiviruses has shaped MxB evolution in primates. We found strong evidence for diversifying selection in the MxB N-terminal tail, which contains molecular determinants of MxB anti-lentivirus specificity. However, we found no overlap between previously-mapped residues that dictate lentiviral restriction and those that have evolved under diversifying selection. Instead, our findings are consistent with MxB having a long-standing and important role in the interferon response to viral infection against a broader range of pathogens than is currently appreciated. Despite its critical role in host innate immunity, we also uncovered multiple functional losses of MxB during mammalian evolution, either by pseudogenization or by gene conversion from MxA genes. Thus, although the majority of mammalian genomes encode two Mx genes, this apparent stasis masks the dramatic effects that recombination and diversifying selection have played in shaping the evolutionary history of Mx genes. Discrepancies between our study and previous publications highlight the need to account for recombination in analyses of positive selection, as well as the importance of using sequence datasets with appropriate depth of divergence. Our study also illustrates that evolutionary analyses of antiviral gene families are critical towards understanding molecular principles that govern host-virus interactions and species-specific susceptibility to viral infection. 相似文献
18.
Why do paralogs persist? Molecular evolution of CYCLOIDEA and related floral symmetry genes in Antirrhineae (Veronicaceae) 总被引:2,自引:0,他引:2
CYCLOIDEA (CYC) and DICHOTOMA (DICH) are paralogous genes that determine adaxial (dorsal) flower identity in the bilaterally symmetric flowers of Antirrhinum majus (snapdragon). We show here that the duplication leading to the existence of both CYC and DICH in Antirrhinum occurred before the radiation of the Antirrhineae (the tribe to which snapdragon belongs). We find no additional gene duplications within Antirrhineae. Using explicit codon-based models of evolution in a likelihood framework, we show that patterns of molecular evolution after the duplication that gave rise to CYC and DICH are consistent with purifying selection acting at both loci, despite their known functional redundancy in snapdragon. However, for specific gene regions, purifying selection is significantly relaxed across DICH lineages, relative to CYC lineages. In addition, we find evidence for relaxed purifying selection along the lineage leading to snapdragon in one of two putative functional domains of DICH. A model of selection accounting for the persistence of paralogous genes in the absence of diversifying selection is presented. This model takes into account differences in the degree of purifying selection acting at the two loci and is consistent with subfunctionalization models of paralogous gene evolution. 相似文献
19.
Malaria continues to be the most lethal protozoan disease of humans. Drug development programs exhibit a high attrition rate and parasite resistance to chemotherapeutic drugs exacerbates the problem. Strategies that limit the development of resistance and minimize host side-effects are therefore of major importance. In this study, a novel approach, termed evolutionary patterning (EP), was used to identify suitable drug target sites that would minimize the emergence of parasite resistance. EP uses the ratio of non-synonymous to synonymous substitutions (omega) to assess the patterns of evolutionary change at individual codons in a gene and to identify codons under the most intense purifying selection (omega < or = 0.1). The extreme evolutionary pressure to maintain these residues implies that resistance mutations are highly unlikely to develop, which makes them attractive chemotherapeutic targets. Method validation included a demonstration that none of the residues providing pyrimethamine resistance in the Plasmodium falciparum dihydrofolate reductase enzyme were under extreme purifying selection. To illustrate the EP approach, the putative P. falciparum glycerol kinase (PfGK) was used as an example. The gene was cloned and the recombinant protein was active in vitro, verifying the database annotation. Parasite and human GK gene sequences were analyzed separately as part of protozoan and metazoan clades, respectively, and key differences in the evolutionary patterns of the two molecules were identified. Potential drug target sites containing residues under extreme evolutionary constraints were selected. Structural modeling was used to evaluate the functional importance and drug accessibility of these sites, which narrowed down the number of candidates. The strategy of evolutionary patterning and refinement with structural modeling addresses the problem of targeting sites to minimize the development of drug resistance. This represents a significant advance for drug discovery programs in malaria and other infectious diseases. 相似文献
20.
Speciation is thought to often result from indirect selection for reproductive isolation. This will occur when reproductive traits that cause reproductive isolation evolve (i) as a by‐product of natural selection on traits with which they are genetically correlated or (ii) as an indirect result of diversifying sexual selection. Here, we use experimental evolution to study the degree of divergent evolution of reproductive traits by manipulating the intensity of natural and sexual selection in replicated selection lines of seed beetles. Following 40 generations of selection, we assayed the degree of divergent evolution of reproductive traits between replicate selection lines experiencing the same selection regime. The evolution of reproductive traits was significantly divergent across selection lines within treatments. The evolution of reproductive traits was both slower and, more importantly, significantly less divergent among lines experiencing stronger directional natural selection. This suggests that reproductive traits did not evolve as an indirect by‐product of adaptation. We discuss several ways in which natural selection may hamper divergent evolution among allopatric populations. 相似文献