Adaptive evolution of G-protein coupled receptor genes

The phylogeny and patterns of nucleotide substitutions in the visual pigment genes, adrenergic receptor genes, muscarinic receptor genes, and in the human mas oncogene were studied by comparing their DNA sequences. The evolutionary tree obtained shows that the visual pigment genes and mas oncogene form one cluster and that the receptor genes form another. In the evolution of rhodopsin genes, synonymous substitutions outnumber nonsynonymous substitutions. This is consistent with the neutral theory of molecular evolution. However, the early evolutionary stages of alpha- and beta-adrenergic and muscarinic receptors are notable for significantly more nonsynonymous substitutions than synonymous substitutions, suggesting the acquisition of novel functional adaptations. Variable rates of nonsynonymous changes in different domains of these proteins reveal DNA segments that might have been important in their functional adaptations.      

SRY基因在人猿超科和旧大陆猴中具有不同的进化规律

通过ＰＣＲ扩增、测序,得到了白臀叶猴和红面猴的ＳＲＹ基因全序列。结合现有的灵长类其他物种序列进行分析,验证了ＨＭＧ盒的保守性。通过构建系统发育树,比较旧大陆猴和人猿超科两个类群内和类群间ＨＭＧ盒侧翼序列Ｋａ／Ｋｓ的比率。有趣的是,人猿超科两物种比较呈现较高的Ｋａ／Ｋｓ比值,但在旧大陆猴中及旧大陆猴与狨猴间的Ｋａ／Ｋｓ比值显著低于人猿超科的,呈现很不同的格局。同时,对于ＨＭＧ盒序列,Ｋａ／Ｋｓ比值在     

Evolutionary differences between alternative and constitutive protein-coding regions of alternatively spliced genes of Drosophila

A total of 790 Drosophila melanogaster genes that are alternatively spliced in a coding region and have orthologs in Drosophila pseudoobscura were studied. It proved that nucleotide substitutions are accumulated in alternative coding regions more rapidly than in constitutive coding regions. Moreover, the evolutionary patterns of alternative regions differing in insertion-deletion mechanisms (use of alternative promoters, splicing sites, or polyadenylation sites) differ significantly. The synonymous substitution rate in coding regions of genes varies more strongly than the nonsynonymous substitution rate. The patterns of substitutions in different classes of alternative regions of Drosophila melanogaster and mammals differ considerably.     

Molecular evolution of hemagglutinin genes of H1N1 swine and human influenza A viruses

Summary The hemagglutinin (HA) genes of influenza type A (H1N1) viruses isolated from swine were cloned into plasmid vectors and their nucleotide sequences were determined. A phylogenetic tree for the HA genes of swine and human influenza viruses was constructed by the neighbor-joining method. It showed that the divergence between swine and human HA genes might have occurred around 1905. The estimated rates of synonymous (silent) substitutions for swine and human influenza viruses were almost the same. For both viruses, the rate of synonymous substitution was much higher than that of nonsynonymous (amino acid altering) substitution. It is the case even for only the antigenic sites of the HA. This feature is consistent with the neutral theory of molecular evolution. The rate of nonsynonymous substitution for human influenza viruses was three times the rate for swine influenza viruses. In particular, nonsynonymous substitutions at antigenic sites occurred less frequently in swine than in humans. The difference in the rate of nonsynonymous substitution between swine and human influenza viruses can be explained by the different degrees of functional constraint operating on the amino acid sequence of the HA in both hosts.     

Relative rates of evolution in the coding and control regions of African mtDNAs

Reduced median networks of African haplogroup L mitochondrial DNA (mtDNA) sequences were analyzed to determine the pattern of substitutions in both the noncoding control and coding regions. In particular, we attempted to determine the causes of the previously reported (Howell et al. 2004) violation of the molecular clock during the evolution of these sequences. In the coding region, there was a significantly higher rate of substitution at synonymous sites than at nonsynonymous sites as well as in the tRNA and rRNA genes. This is further evidence for the operation of purifying selection during human mtDNA evolution. For most sites in the control region, the relative rate of substitution was similar to the rate of neutral evolution (assumed to be most closely approximated by the substitution rate at 4-fold degenerate sites). However, there are a number of mutational hot spots in the control region, approximately 3% of the total sites, that have a rate of substitution greater than the neutral rate, at some sites by more than an order of magnitude. It is possible either that these sites are evolving under conditions of positive selection or that the substitution rate at some sites in the control region is strongly dependent upon sequence context. Finally, we obtained preliminary evidence for "nonideal" evolution in the control region, including haplogroup-specific substitution patterns and a decoupling between relative rates of substitution in the control and coding regions.     

Pattern of Nucleotide Substitutions in Growth Hormone-Prolactin Gene Family: A Paradigm for Evolution by Gene Duplication

The growth hormone-prolactin gene family in mammals is an interesting example of evolution by gene duplication. Divergence among members of duplicated gene families and among species was examined by using reported gene sequences of growth hormone, prolactin and their receptors. Sequence divergence among species was found to show a general tendency in which a generation-time effect is pronounced for synonymous substitutions but not so for nonsynonymous substitutions. Divergence among duplicated genes is characterized by the relatively high rate of nonsynonymous substitutions, i.e., the rate is close to that of synonymous ones. In view of the stage- and tissue-specific expression of duplicated genes, some of the amino acid substitutions among duplicated genes is likely to be caused by positive Darwinian selection.     

Different patterns of evolution in alternative and constitutive coding regions of Drosophila alternatively spliced genes

Seven hundred and ninety Drosophila melanogaster genes, alternatively spliced in coding regions were considered together with their Drosophila pseudoobscura orthologs. It was found that nucleotide substitutions in alternative coding regions accumulate more intensively than in constitutive regions. Moreover, the evolutionary pattern of alternative regions depends on their inclusion mechanisms (use of alternative promoters, splicing sites or polyadenylation sites) significantly. The rate of synonymous substitutions varies is more dramatically than that of nonsynonymous substitutions. Nucleotide substitution patterns in different classes of alternative regions of mammalian and Drosophila genes have little in common.     

Synonymous and nonsynonymous substitutions in mammalian genes and the nearly neutral theory

The nearly neutral theory of molecular evolution predicts larger generation-time effects for synonymous than for nonsynonymous substitutions. This prediction is tested using the sequences of 49 single-copy genes by calculating the average and variance of synonymous and nonsynonymous substitutions in mammalian star phylogenies (rodentia, artiodactyla, and primates). The average pattern of the 49 genes supports the prediction of the nearly neutral theory, with some notable exceptions.The nearly neutral theory also predicts that the variance of the evolutionary rate is larger than the value predicted by the completely neutral theory. This prediction is tested by examining the dispersion index (ratio of the variance to the mean), which is positively correlated with the average substitution number. After weighting by the lineage effects, this correlation almost disappears for nonsynonymous substitutions, but not quite so for synonymous substitutions. After weighting, the dispersion indices of both synonymous and nonsynonymous substitutions still exceed values expected under the simple Poisson process. The results indicate that both the systematic bias in evolutionary rate among the lineages and the episodic type of rate variation are contributing to the large variance. The former is more significant to synonymous substitutions than to nonsynonymous substitutions. Isochore evolution may be similar to synonymous substitutions. The rate and pattern found here are consistent with the nearly neutral theory, such that the relative contributions of drift and selection differ between the two types of substitutions. The results are also consistent with Gillespie's episodic selection theory.     

Molecular Evolution of Prolactin in Primates

Pituitary prolactin, like growth hormone (GH) and several other protein hormones, shows an episodic pattern of molecular evolution in which sustained bursts of rapid change contrast with long periods of slow evolution. A period of rapid change occurred in the evolution of prolactin in primates, leading to marked sequence differences between human prolactin and that of nonprimate mammals. We have defined this burst more precisely by sequencing the coding regions of prolactin genes for a prosimian, the slow loris (Nycticebus pygmaeus), and a New World monkey, the marmoset (Callithrix jacchus). Slow loris prolactin is very similar in sequence to pig prolactin, so the episode of rapid change occurred during primate evolution, after the separation of lines leading to prosimians and higher primates. Marmoset prolactin is similar in sequence to human prolactin, so the accelerated evolution occurred before divergence of New World monkeys and Old World monkeys/apes. The burst of change was confined largely to coding sequence (nonsynonymous sites) for mature prolactin and is not marked in other components of the gene sequence. This and the observations that (1) there was no apparent loss of function during the episode of rapid evolution, (2) the rate of evolution slowed toward the basal rate after this burst, and (3) the distribution of substitutions in the prolactin molecule is very uneven support the idea that this episode of rapid change was due to positive adaptive selection. In the slow loris and marmoset there is no evidence for duplication of the prolactin gene, and evidence from another New World monkey (Cebus albifrons) and from the chimpanzee and human genome sequences, suggests that this is the general position in primates, contrasting with the situation for GH genes. The chimpanzee prolactin sequence differs from that of human at two residues and comparison of human and chimpanzee prolactin gene sequences suggests that noncoding regions associated with regulating expression may be evolving differently from other noncoding regions.     

Variable evolutionary rates in the molecular evolution of mammalian growth hormones

In mammals pituitary growth hormone (GH) shows a slow basal rate of evolution (0.22 ± 0.03 × 10^–9 substitutions/amino acid site/year) which appears to have increased by at least 25–50-fold on two occasions, during the evolution of primates (to at least 10.8 ± 1.3 X 10^–9 substitutions/amino acid site/year) and artiodactyl ruminants (to at least 5.6 ± 1.3 X 10^–9 substitutions/amino acid site/year). That these rate increases are real, and not due to inadvertent comparison of nonorthologous genes, was established by showing that features of the GH gene sequences that are not expressed as mature hormone do not show corresponding changes in evolutionary rate. Thus, analysis of nonsynonymous substitutions in the coding sequence for the mature protein confirmed the rate increases seen in the primate and ruminant GHs, but analysis of nonsynonymous substitutions in the signal peptide sequence, synonymous substitutions in the coding sequence for signal peptide or mature protein, and 5 and 3 untranslated sequences showed no statistically significant changes in evolutionary rate. Evidence that the increases in evolutionary rate are probably due to positive selection is provided by the observation that in the cases of both ruminant and primate GHs the periods of rapid evolution were followed by a return to a slow rate similar to the basal rate seen in other mammalian GHs. Differences between the biological properties of GHs have been identified which may relate to these periods of rapid adaptive molecular evolution. On the basis of sequence data currently available (but excluding rodent GHs which show an intermediate rate, the basis of which is not clear) for most (90%) of evolutionary time mammalian GHs have been in the slow phase of evolution, with possibly most of the few amino acid substitutions that have occurred being neutral in nature. But most (80%) of the amino acid substitutions that have been introduced into GH during the course of mammalian evolution have been accepted during the rapid phases and were adaptive in nature.     

Molecular evolution of cadherin-related neuronal receptor/protocadherin(alpha) (CNR/Pcdh(alpha)) gene cluster in Mus musculus subspecies

The mouse cadherin-related neuronal receptor/protocadherin (CNR/Pcdh) gene clusters are located on chromosome 18. We sequenced single-nucleotide polymorphisms (SNPs) of the CNR/Pcdh(alpha)-coding region among 12 wild-derived and four laboratory strains; these included the four major subspecies groups of Mus musculus: domesticus, musculus, castaneus, and bactrianus. We detected 883 coding SNPs (cSNPs) in the CNR/Pcdh(alpha) variable exons and three in the constant exons. Among all the cSNPs, 586 synonymous (silent) and 297 nonsynonymous (amino acid exchanged) substitutions were found; therefore, the K(a)/K(s) ratio (nonsynonymous substitutions per synonymous substitution) was 0.51. The synonymous cSNPs were relatively concentrated in the first and fifth extracellular cadherin domain-encoding regions (ECs) of CNR/Pcdh(alpha). These regions have high nucleotide homology among the CNR/Pcdh(alpha) paralogs, suggesting that gene conversion events in synonymous and homologous regions of the CNR/Pcdh(alpha) cluster are related to the generation of cSNPs. A phylogenetic analysis revealed gene conversion events in the EC1 and EC5 regions. Assuming that the common sequences between rat and mouse are ancestral, the GC content of the third codon position has increased in the EC1 and EC5 regions, although biased substitutions from GC to AT were detected in all the codon positions. In addition, nonsynonymous substitutions were extremely high (11 of 13, K(a)/K(s) ratio 5.5) in the laboratory mouse strains. The artificial environment of laboratory mice may allow positive selection for nonsynonymous amino acid variations in CNR/Pcdh(alpha) during inbreeding. In this study, we analyzed the direction of cSNP generation, and concluded that subspecies-specific nucleotide substitutions and region-restricted gene conversion events may have contributed to the generation of genetic variations in the CNR/Pcdh genes within and between species.     

Synonymous Substitutions in the Xdh Gene of Drosophila: Heterogeneous Distribution along the Coding Region

The Xdh (rosy) region of Drosophila subobscura has been sequenced and compared to the homologous region of D. pseudoobscura and D. melanogaster. Estimates of the numbers of synonymous substitutions per site (Ks) confirm that Xdh has a high synonymous substitution rate. The distributions of both nonsynonymous and synonymous substitutions along the coding region were found to be heterogeneous. Also, no relationship has been detected between Ks estimates and codon usage bias along the gene, in contrast with the generally observed relationship among genes. This heterogeneous distribution of synonymous substitutions along the Xdh gene, which is expression-level independent, could be explained by a differential selection pressure on synonymous sites along the coding region acting on mRNA secondary structure. The synonymous rate in the Xdh coding region is lower in the D. subobscura than in the D. pseudoobscura lineage, whereas the reverse is true for the Adh gene.     

Hotspots of Biased Nucleotide Substitutions in Human Genes

Genes that have experienced accelerated evolutionary rates on the human lineage during recent evolution are candidates for involvement in human-specific adaptations. To determine the forces that cause increased evolutionary rates in certain genes, we analyzed alignments of 10,238 human genes to their orthologues in chimpanzee and macaque. Using a likelihood ratio test, we identified protein-coding sequences with an accelerated rate of base substitutions along the human lineage. Exons evolving at a fast rate in humans have a significant tendency to contain clusters of AT-to-GC (weak-to-strong) biased substitutions. This pattern is also observed in noncoding sequence flanking rapidly evolving exons. Accelerated exons occur in regions with elevated male recombination rates and exhibit an excess of nonsynonymous substitutions relative to the genomic average. We next analyzed genes with significantly elevated ratios of nonsynonymous to synonymous rates of base substitution (d_N/d_S) along the human lineage, and those with an excess of amino acid replacement substitutions relative to human polymorphism. These genes also show evidence of clusters of weak-to-strong biased substitutions. These findings indicate that a recombination-associated process, such as biased gene conversion (BGC), is driving fixation of GC alleles in the human genome. This process can lead to accelerated evolution in coding sequences and excess amino acid replacement substitutions, thereby generating significant results for tests of positive selection.     

Population genomics of eusocial insects: the costs of a vertebrate‐like effective population size

The evolution of reproductive division of labour and social life in social insects has lead to the emergence of several life‐history traits and adaptations typical of larger organisms: social insect colonies can reach masses of several kilograms, they start reproducing only when they are several years old, and can live for decades. These features and the monopolization of reproduction by only one or few individuals in a colony should affect molecular evolution by reducing the effective population size. We tested this prediction by analysing genome‐wide patterns of coding sequence polymorphism and divergence in eusocial vs. noneusocial insects based on newly generated RNA‐seq data. We report very low amounts of genetic polymorphism and an elevated ratio of nonsynonymous to synonymous changes – a marker of the effective population size – in four distinct species of eusocial insects, which were more similar to vertebrates than to solitary insects regarding molecular evolutionary processes. Moreover, the ratio of nonsynonymous to synonymous substitutions was positively correlated with the level of social complexity across ant species. These results are fully consistent with the hypothesis of a reduced effective population size and an increased genetic load in eusocial insects, indicating that the evolution of social life has important consequences at both the genomic and population levels.     

Testing the neutral theory of molecular evolution using genomic data: a comparison of the human and bovine transcriptome

Despite growing evidence of rapid evolution in protein coding genes, the contribution of positive selection to intra- and interspecific differences in protein coding regions of the genome is unclear. We attempted to see if genes coding for secreted proteins and genes with narrow expression, specifically those preferentially expressed in the mammary gland, have diverged at a faster rate between domestic cattle (Bos taurus) and humans (Homo sapiens) than other genes and whether positive selection is responsible. Using a large data set, we identified groups of genes based on secretion and expression patterns and compared them for the rate of nonsynonymous (dN) and synonymous (dS) substitutions per site and the number of radical (Dr) and conservative (Dc) amino acid substitutions. We found evidence of rapid evolution in genes with narrow expression, especially for those expressed in the liver and mammary gland and for genes coding for secreted proteins. We compared common human polymorphism data with human-cattle divergence and found that genes with high evolutionary rates in human-cattle divergence also had a large number of common human polymorphisms. This argues against positive selection causing rapid divergence in these groups of genes. In most cases dN/dS ratios were lower in human-cattle divergence than in common human polymorphism presumably due to differences in the effectiveness of purifying selection between long-term divergence and short-term polymorphism.