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Results for “Purifying selection”

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PubMed1996

On transition bias in mitochondrial genes of pocket gophers.

The relative contribution of mutation and purifying selection to transition bias has not been quantitatively assessed in mitochondrial protein genes. The observed transition/transversion (s/v) ratio is (micros Ps)/(microv Pv), where micros and microv denote mutation rate of transitions and transversions, respectively, and Ps and Pv denote fixation probabilities of transitions and transversions, respectively. Because selection against synonymous transitions can be assumed to be roughly equal to that against synonymous transversions, Ps/Pv approximately 1 at fourfold degenerate sites, so that the s/v ratio at fourfold degenerate sites is approximately micros/microv, which is a measure of mutational contribution to transition bias. Similarly, the s/v ratio at nondegenerate sites is also an estimate of micros/microv if we assume that selection against nonsynonymous transitions is roughly equal to that against nonsynonymous transversions. In two mitochondrial genes, cytochrome oxidase subunit I (COI) and cytochrome b (cyt-b) in pocket gophers, the s/v ratio is about two at nondegenerate and fourfold degenerate sites for both the COI and the cyt-b genes. This implies that mutation contribution to transition bias is relatively small. In contrast, the s/v ratio is much greater at twofold degenerate sites, being 48 for COI and 40 for cyt-b. Given that the micros/microv ratio is about 2, the Ps/Pv ratio at twofold degenerate sites must be on the order of 20 or greater. This suggests a great effect of purifying selection on transition bias in mitochondrial protein genes because transitions are synonymous and transversions are nonsynonymous at twofold degenerate sites in mammalian mitochondrial genes. We also found that nonsynonymous mutations at twofold degenerate sites are more neutral than nonsynonymous mutations at nondegenerate sites, and that the COI gene is subject to stronger purifying selection than is the cyt-b gene. A model is presented to integrate the effect of purifying selection, codon bias, DNA repair and GC content on s/v ratio of protein-coding genes.

Analysis of Variance↗

PubMed2005

Positive and negative selection on mammalian Y chromosomes.

Y chromosomes are genetically degenerate in most organisms studied. The loss of genes from Y chromosomes is thought to be due to the inefficiency of purifying selection in nonrecombining regions, which leads to the accumulation of deleterious mutations via the processes of hitchhiking, background selection, and Muller's ratchet. As the severity of these processes depends on the number of functional genes linked together on the nonrecombining Y, it is not clear whether these processes are still at work on the old, gene-poor mammalian Y chromosomes. If purifying selection is indeed less efficient in the Y-linked, compared to the X-linked genes, deleterious nonsynonymous substitutions are expected to accumulate faster on the Y chromosome. However, positive selection on Y-linked genes could also increase the rate of amino acid-changing substitutions. Thus, the previous reports of an elevated nonsynonymous substitution rate in Y-linked genes are still open to interpretation. Here, we report evidence for positive selection in two out of three studied mammalian Y-linked genes, suggesting that adaptive Darwinian evolution may be common on mammalian Y chromosomes. Taking positive selection into account, we demonstrate that purifying selection is less efficient in mammalian Y-linked genes compared to their X-linked homologues, suggesting that these genes continue to degenerate.

Animals↗

PubMed2006

Selective pressures at a codon-level predict deleterious mutations in human disease genes.

Deleterious mutations affecting biological function of proteins are constantly being rejected by purifying selection from the gene pool. The non-synonymous/synonymous substitution rate ratio (omega) is a measure of selective pressure on amino acid replacement mutations for protein-coding genes. Different methods have been developed in order to predict non-synonymous changes affecting gene function. However, none has considered the estimation of selective constraints acting on protein residues. Here, we have used codon-based maximum likelihood models in order to estimate the selective pressures on the individual amino acid residues of a well-known model protein: p53. We demonstrate that the number of residues under strong purifying selection in p53 is much higher than those that are strictly conserved during the evolution of the species. In agreement with theoretical expectations, residues that have been noted to be of structural relevance, or in direct association with DNA, were among those showing the highest signals of purifying selection. Conversely, those changing according to a neutral, or nearly neutral mode of evolution, were observed to be irrelevant for protein function. Finally, using more than 40 human disease genes, we demonstrate that residues evolving under strong selective pressures (omega<0.1) are significantly associated (p<0.01) with human disease. We hypothesize that non-synonymous change on amino acids showing omega<0.1 will most likely affect protein function. The application of this evolutionary prediction at a genomic scale will provide an a priori hypothesis of the phenotypic effect of non-synonymous coding single nucleotide polymorphisms (SNPs) in the human genome.

Amino Acid Sequence↗

PubMed2005

Patterns of nucleotide difference in overlapping and non-overlapping reading frames of papillomavirus genomes.

On the basis of a phylogenetic analysis of papillomavirus complete genomes, 30 pairs of closely related genomes were chosen for examination of the pattern of synonymous and non-synonymous nucleotide difference in overlapping and non-overlapping reading frames. The proportion of synonymous differences per synonymous site (pS) was generally reduced in overlapping regions in comparison to non-overlapping regions. This reduction in pS appears to result from purifying selection acting on the overlapping reading frame because of functional constraint on the amino acid sequence that it encodes. As a consequence of such purifying selection, a trade-off was observed between synonymous substitution in one reading frame and non-synonymous substitution in the other; this pattern was particularly evident in the overlap between the E2 and E1 reading frames, which encodes a highly conserved portion of the E2 protein. Fifty-three sequences of the hinge region of the HPV16 E2 protein (where the E2 and E4 reading frames overlap) showed an elevated level of non-synonymous nucleotide substitution in the E2 reading frame, particularly in a region believed to be involved in immune recognition. Non-synonymous substitutions in this region occurred disproportionately in such a way as to cause synonymous substitutions in the E4 reading frame. Thus, positive diversifying selection on the E2 hinge region appears to coexist with purifying selection on the overlapping region of E4.

Base Sequence↗

PubMed2002

Phosphoglucose isomerases of hagfish, zebrafish, gray mullet, toad, and snake, with reference to the evolution of the genes in vertebrates.

Phosphoglucose isomerase (PGI) is a protein with multiple functions. To infer its structure changes and evolution in vertebrates, we cloned cDNAs encoding PGI genes from hagfish (Paramyxine yangi), gray mullet (Mugil cephalus), zebrafish (Danio rerio), toad (Bufo melanosticus), and snake (Boiga kraepelini). Only one PGI gene was cloned in each of hagfish, toad, and snake, but two PGI genes were found in zebrafish and gray mullet, respectively. The PGI of hagfish encodes 554 amino acids, in contrast to the PGIs of bonyfishes, toad, and snake which encode 553 amino acids and the PGIs of mammals which encode 558 amino acids. Among 558 aligned amino acid sites, there are 314 sites (56.27%) totally conserved. To see if diversifying selection acts on PGI amino acids of vertebrates, we calculated the pairwise ratio of nonsynonymous versus synonymous substitution per site (Ka/Ks) and the ratio of radical amino acid changes versus conservative amino acid changes per sites (dR/dC) between PGI sequences. The average pairwise ratio between nonsynonymous substitutions per nucleotide (Ka) and synonymous substitutions per nucleotide (Ks) among vertebrate PGI sequences equals 0.047 +/- 0.019. The average pairwise ratio between radical amino acid changes and conservative amino acid changes (dR/dC) among the vertebrate PGIs equal 0.938 +/- 0.158 for charge changes, 0.558 +/- 0.085 for polarity changes, and 0.465 +/- 0.0714 when both polarity and volume are considered. There is no amino acid within the vertebrate PGIs under diversifying selection as analyzed by the method of Yang et al. (2000b). The results suggest that the present vertebrate PGIs are at evolutionary stasis and are being subjected to intense purifying selection. The purifying selection is to maintain polarity and volume of the protein but not the charge groups of amino acids. Phylogenetic analysis reveals that vertebrate PGIs can be classified into three major groups: the mammalian, amphibian-reptilian, and teleostean PGIs. The gene tree suggests that the gene duplication event of PGI in bonyfishes occurred before diversification of Acanthopterygii but after the split of bonyfishes and tetrapods. The evolution of multiple functions of PGI is discussed.

Amino Acid Sequence↗

PubMed2006

Positive selection of the Hrp pilin HrpE of the plant pathogen Xanthomonas.

The plant-pathogenic bacterium Xanthomonas campestris pv. vesicatoria possesses a type III secretion (TTS) system which is encoded by the 23-kb hrp (hypersensitive response and pathogenicity) gene cluster. The TTS system is necessary for pathogenicity in susceptible hosts and induction of the hypersensitive response in resistant plants. At the cell surface, the TTS system is associated with an extracellular filamentous structure, the Hrp pilus, which serves as a conduit for the transfer of bacterial proteins into the plant cell cytosol. The major pilus component, the HrpE pilin, is unique to xanthomonads. Previous work showed that HrpE contains two regions: a hypervariable surface-exposed domain, including the N-terminal secretion signal, and a C-terminal polymerization domain. In this study, the evolutionary rate of the hrpE gene was analyzed. Twenty-one alleles were cloned, sequenced, and compared with five known hrpE alleles. The ratio of synonymous (K(s)) and nonsynonymous (K(a)) substitution rates shows that parts of the HrpE N terminus are subjected to positive selection and the C terminus is subjected to purifying selection. The trade-off between positive and purifying selection at the very-N terminus allowed us to ascertain the amphipathic alpha-helical nature of the TTS signal. This is the first report of a surface structure from a plant-pathogenic bacterium that evolved under the constraint of positive selection and hints to the evolutionary adaptation of this extracellular appendage to avoid recognition by the plant defense surveillance system.

Adaptation, Physiological↗

PubMed2003

Heterogeneous selection on LEGCYC paralogs in relation to flower morphology and the phylogeny of Lupinus (Leguminosae).

An analysis of the molecular evolution of two LEGCYC paralogs in Lupinus (Genisteae: Leguminosae) reveals a varied history of site-specific and lineage-specific evolutionary rates and selection both within and between loci. LEGCYC genes are homologous to regulatory loci known to control floral symmetry and adaxial flower organ identity in Antirrhinum and its relatives. Within Lupinus, L. densiflorus is unusual in having flowers with a proportionally smaller standard (upright adaxial petals) and larger wings (lateral petals) than other lupin species. Phylogenetic estimates of the nonsynonymous/synonymous substitution rate ratio, omega, suggest that along the L. densiflorus lineage, positive selection (omega > 1) acted at some codon sites of one paralog, LEGCYC1B, and greater purifying selection (omega < 1) acted at some sites of the other paralog, LEGCYC1A. Overall, LEGCYC1A appears to be evolving faster than LEGCYC1B, and both paralogs are evolving faster than the internal transcribed spacer (ITS) region of nr DNA. The predominant historical pattern inferred is a highly heterogeneous "selectional mosaic" which we suggest may be typical of the teosinte branched 1-cycloidea-PCF (TCP) class of transcriptional activators, and possibly other genes. Codon models that do not account for both site-specific and lineage-specific variation in omega do not detect positive selection at these loci. We suggest a modification of existing branch-site models involving an additional omega parameter along the foreground branch, to account for the effects of both greater positive selection and greater purifying selection at different codon sites along a particular branch. The higher rates of evolution and congruent phylogenetic signal of both LEGCYC paralogs show promise for the use of these genes as markers for phylogeny reconstruction at low taxonomic levels in Genisteae [corrected]

Amino Acid Substitution↗

PubMed2005

Evolutionary analysis of genetic variation observed in citrus tristeza virus (CTV) after host passage.

We have studied the genetic variability in two genes (p18 and p20) from two groups of Citrus tristeza virus (CTV) isolates. One group (isolates T385, T317, T318, and T305) was derived from a Spanish source by successive host passages while the other (isolates T388 and T390) was obtained after aphid transmission from a Japanese source. A total of 274 sequences were obtained for gene p18 and 451 for p20. In the corresponding phylogenetic trees, sequences derived from the severe isolates (T318, T305, and T388) clustered together and separately from those derived from mild or moderate isolates (T385, T317, and T390), regardless of their geographic origin. Hierarchical analyses of molecular variance showed that up to 53% of the total genetic variability in p18 and up to 87% of the variation in p20 could be explained by differences in the pathogenicity features of the isolates. Neutrality tests revealed that different selection forces had been acting between isolates and between genes, with purifying selection being suggested for p18 from isolates T385 and T390 and for p20 from isolates T385, T317, and T388, and balancing selection for p18 from isolates T318, T305, and T388 and for p20 from isolates T318 and T390. Furthermore, several models of codon selection were observed, with purifying selection being the most notable one, compatible with low effective population size of the virus populations resulting from transmission bottlenecks. We found no evidence of recombination playing a significant role during p18 and p20 evolution in these isolates. These results suggest that hosts can be an important evolutionary factor for CTV isolates.

Animals↗

PubMed2005

Evolutionary constraints in conserved nongenic sequences of mammals.

Mammalian genomes contain many highly conserved nongenic sequences (CNGs) whose functional significance is poorly understood. Sets of CNGs have previously been identified by selecting the most conserved elements from a chromosome or genome, but in these highly selected samples, conservation may be unrelated to purifying selection. Furthermore, conservation of CNGs may be caused by mutation rate variation rather than selective constraints. To account for the effect of selective sampling, we have examined conservation of CNGs in taxa whose evolution is largely independent of the taxa from which the CNGs were initially identified, and we have controlled for mutation rate variation in the genome. We show that selective constraints in CNGs and their flanks are about one-half as strong in hominids as in murids, implying that hominids have accumulated many slightly deleterious mutations in functionally important nongenic regions. This is likely to be a consequence of the low effective population size of hominids leading to a reduced effectiveness of selection. We estimate that there are one and two times as many conserved nucleotides in CNGs as in known protein-coding genes of hominids and murids, respectively. Polymorphism frequencies in CNGs indicate that purifying selection operates in these sequences. During hominid evolution, we estimate that a total of about three deleterious mutations in CNGs and protein-coding genes have been selectively eliminated per diploid genome each generation, implying that deleterious mutations are eliminated from populations non-independently and that sex is necessary for long-term population persistence.

Animals↗

PubMed2003

Selection on the genes of Euplotes crassus Tec1 and Tec2 transposons: evolutionary appearance of a programmed frameshift in a Tec2 gene encoding a tyrosine family site-specific recombinase.

The Tec1 and Tec2 transposons of the ciliate Euplotes crassus carry a gene for a tyrosine-type site-specific recombinase. The expression of the Tec2 gene apparently uses a programmed +1 frameshift. To test this hypothesis, we first examined whether this gene has evolved under purifying selection in Tec1 and Tec2. Each element carries three genes, and each has evolved under purifying selection for the function of its encoded protein, as evidenced by a dearth of nonsynonymous changes. This distortion of divergence is apparent in codons both 5' and 3' of the frameshift site. Thus, Tec2 transposons have diverged from each other while using a programmed +1 frameshift to produce recombinase, the function of which is under purifying selection. What might this function be? Tyrosine-type site-specific recombinases are extremely rare in eukaryotes, and Tec elements are the first known eukaryotic type II transposons to encode a site-specific recombinase. Tec elements also encode a widespread transposase. The Tec recombinase might function in transposition, resolve products of transposition (bacterial replicative transposons use recombinase or resolvase to separate joined replicons), or provide a function that benefits the ciliate host. Transposons in ciliated protozoa are removed from the macronucleus, and it has been proposed that the transposons provide this "excisase" activity.

Animals↗

PubMed2004

Gene conversion and functional divergence in the beta-globin gene family.

Different models of gene family evolution have been proposed to explain the mechanism whereby gene copies created by gene duplications are maintained and diverge in function. Ohta proposed a model which predicts a burst of nonsynonymous substitutions following gene duplication and the preservation of duplicates through positive selection. An alternative model, the duplication-degeneration-complementation (DDC) model, does not explicitly require the action of positive Darwinian selection for the maintenance of duplicated gene copies, although purifying selection is assumed to continue to act on both copies. A potential outcome of the DDC model is heterogeneity in purifying selection among the gene copies, due to partitioning of subfunctions which complement each other. By using the d(N)/ d(S) (omega) rate ratio to measure selection pressure, we can distinguish between these two very different evolutionary scenarios. In this study we investigated these scenarios in the beta-globin family of genes, a textbook example of evolution by gene duplication. We assembled a comprehensive dataset of 72 vertebrate beta-globin sequences. The estimated phylogeny suggested multiple gene duplication and gene conversion events. By using different programs to detect recombination, we confirmed several cases of gene conversion and detected two new cases. We tested evolutionary scenarios derived from Ohta's model and the DDC model by examining selective pressures along lineages in a phylogeny of beta-globin genes in eutherian mammals. We did not find significant evidence for an increase in the omega ratio following major duplication events in this family. However, one exception to this pattern was the duplication of gamma-globin in simian primates, after which a few sites were identified to be under positive selection. Overall, our results suggest that following gene duplications, paralogous copies of beta-globin genes evolved under a nonepisodic process of functional divergence.

Animals↗

PubMed2005

Distribution and intensity of constraint in mammalian genomic sequence.

Comparisons of orthologous genomic DNA sequences can be used to characterize regions that have been subject to purifying selection and are enriched for functional elements. We here present the results of such an analysis on an alignment of sequences from 29 mammalian species. The alignment captures approximately 3.9 neutral substitutions per site and spans approximately 1.9 Mbp of the human genome. We identify constrained elements from 3 bp to over 1 kbp in length, covering approximately 5.5% of the human locus. Our estimate for the total amount of nonexonic constraint experienced by this locus is roughly twice that for exonic constraint. Constrained elements tend to cluster, and we identify large constrained regions that correspond well with known functional elements. While constraint density inversely correlates with mobile element density, we also show the presence of unambiguously constrained elements overlapping mammalian ancestral repeats. In addition, we describe a number of elements in this region that have undergone intense purifying selection throughout mammalian evolution, and we show that these important elements are more numerous than previously thought. These results were obtained with Genomic Evolutionary Rate Profiling (GERP), a statistically rigorous and biologically transparent framework for constrained element identification. GERP identifies regions at high resolution that exhibit nucleotide substitution deficits, and measures these deficits as "rejected substitutions". Rejected substitutions reflect the intensity of past purifying selection and are used to rank and characterize constrained elements. We anticipate that GERP and the types of analyses it facilitates will provide further insights and improved annotation for the human genome as mammalian genome sequence data become richer.

Animals↗

PubMed2005

The prion protein gene in humans revisited: lessons from a worldwide resequencing study.

Ample evidence has accumulated showing that different coding variants of the PRNP gene confer differential susceptibility for prion diseases. Here we evaluate the patterns of nucleotide variation in PRNP exon 2, which includes all the protein-coding sequence, by resequencing a worldwide sample of 174 humans for 2378 bp. In line with previous studies, we found two main haplotypes differentiated by nonsynonymous substitution in codon 129. Our analyses reveal the worldwide pattern of variation at the PRNP gene to be inconsistent with neutral expectations, indicating instead an excess of low-frequency variants, a footprint of the action of either positive or purifying selection. A comparison of neutrality test statistics for PRNP with other human genes indicates that the signal of positive selection on PRNP is stronger than expected from a possible confounding genome-wide background signal of population expansion. Two main conclusions arise from our analysis. First, the existence of an ancient, stable, balanced polymorphism that has been claimed in a previous study and related to cannibalism can be rejected and is shown to be due to ascertainment bias. Second, our results are consistent with a complex history of selection including mainly positive selection, even if short local periods of balancing selection (Kuru-like episodes), or even a weak purifying selection model, are consistent with our data.

Amino Acid Substitution↗

PubMed1993

Fatty liver hemorrhagic syndrome in hens overfed a purified diet. Selected enzyme activities and liver histology in relation to liver hemorrhage and reproductive performance.

A nutritionally adequate, purified diet was developed and used in studies to characterize selected aspects of laying hens in which fatty liver hemorrhagic syndrome (FLHS) was induced by overfeeding. Hens consuming the diet ad libitum or intubated with the diet in quantities equivalent to usual daily energy intake maintained normal rates of lay, did not become obese, and did not develop liver hemorrhage. Overfed hens had a 33% incidence of FLHS, as indicated by the presence of severe liver hemorrhage score, and displayed the full range of symptoms associated with spontaneous outbreaks of FLHS, including definitive lesions of hepatic reticulin. Among four groups of hens clinically classified according to rates of liver hemorrhage and egg production, there were no differences noted in total liver fat, liver fat concentration, or final body weight. Liver hemorrhage was associated with the degree of induction of liver lipogenic accessory enzymes. Serum enzyme activities indicate that overfed hens, unlike the overfed goose, retain hepatocellular membrane integrity. Overfeeding caused altered reproductive performance in 72% of hens. Alterations included erratic laying, increased incidence of double ovulations, shell defects, follicular collapse, and oviduct involution. Pattern of lay preceding necropsy seemed to influence follicle weight at necropsy. The data presented re-emphasize the interdependence among liver, ovary, and oviduct function in the etiology of FLHS.

Animal Feed↗

PubMed2001

Evolution of nuclear- and mitochondrial-encoded subunit interaction in cytochrome c oxidase.

Mitochondrial DNA (mtDNA)-encoded proteins function in eukaryotes as subunits of respiratory complexes that also contain nuclear DNA (nDNA)-encoded subunits. The importance of functional interactions between mtDNA- and nDNA-encoded proteins was previously demonstrated by testing the survivability of cybrid cells or individuals containing nDNA and mtDNA from different populations or species. This report focuses on the multisubunit respiratory complex cytochrome c oxidase (COX), made up of both mtDNA-encoded and nDNA-encoded subunits. A combination of evolutionary and crystallographic data is employed to determine whether rates of nonsynonymous substitutions have been higher, the same, or lower for residues in close proximity that are encoded by a different genome (nDNA or mtDNA). This determination is performed by simply taking the ratio, called the interaction ratio i, of the nonsynonymous substitution rate of the close-contact residues to the nonsynonymous substitution rate of the noncontact residues. We assume that the close-contact residues (which are more likely to interact) are functionally important and that, therefore, amino acid replacements among these residues cannot escape the scrutiny of natural selection. i = 1 indicates that the close-contact residues have been under neither greater purifying selection nor greater positive selection than the noncontact residues as a specific consequence of their being encoded by separate genomes. i < 1 indicates that the close-contact residues have been under greater purifying selection but less positive selection than have the noncontact residues. Conversely, i > 1 indicates that the close-contact residues have been under less purifying but greater positive selection than have the noncontact residues. i < 1 may be referred to as a constraining interaction; i.e., the close-contact residues compared with the noncontact residues appear to be under greater structural-functional constraints. On the other hand, i > 1 may be referred to as an optimizing interaction; i.e., apparently many different amino acid replacements are required to optimize this subunit's interaction with the other subunit. A major finding is that the nDNA-encoded residues in close physical proximity to mtDNA-encoded residues evolve more slowly than the other nuclear-encoded residues (and thus display a constraining interaction), whereas the mtDNA-encoded residues in close physical proximity to nDNA-encoded residues evolve more rapidly than the other mitochondrial-encoded residues (and thus display an optimizing interaction). A possible reason for this striking difference between the nuclear- and mitochondrial-encoded COX subunits in how their functional interaction evolves is discussed.

Amino Acid Substitution↗

PubMed2026

Co-mutation Based Genetic Networks to Infer Temporal Mutation Dynamics in Ancient Human Mitochondrial Genomes.

The evolutionary history of Homo sapiens is marked by complex interactions between environmental, cultural, and genetic factors. To investigate the molecular signatures of these processes, we analyzed ancient mitochondrial DNA (mtDNA) across temporal and geographic contexts using principles of co-occurrence of minor alleles defined as co-mutation, through spatiotemporal co-mutation networks of variable sites. Haplogroup-based assessments of variable sites revealed a major transition from foraging to agrarian lifestyles during the Copper-Bronze Age. Genetic network analyses demonstrated that COX and CYB loci exhibited distinct temporal dynamics, with their interactions modulated by NADH dehydrogenase genes in a geological age-dependent manner. To complement the network approach, we constructed phylogeny-based gene interaction networks and assessed polymorphism-to-divergence from chimpanzee ratios. The tree-based networks displayed topologies consistent with co-mutation analyses but showed reduced gene-gene connectivity. Polymorphism/divergence analysis further indicated that the CYB gene has been under long-term purifying selection, whereas ATP6, COX, and NADH dehydrogenase genes experienced episodic purifying selection aligned with distinct historical phases. Collectively, our findings demonstrate that network-based analysis of ancient mtDNA provides insights into early human lifestyle transitions and haplogroup diversification, contributing to the evolutionary foundations of modern human populations.

Ancient humans↗

PubMed2005

Evidence for heterogeneous selective pressures in the evolution of the env gene in different human immunodeficiency virus type 1 subtypes.

Recent studies have demonstrated the emergence of human immunodeficiency virus type 1 (HIV-1) subtypes with various levels of fitness. Using heterogeneous maximum-likelihood models of adaptive evolution implemented in the PAML software package, with env sequences representing each HIV-1 group M subtype, we examined the various intersubtype selective pressures operating across the env gene. We found heterogeneity of evolutionary mechanisms between the different subtypes with a category of amino acid sites observed that had undergone positive selection for subtypes C, F1, and G, while these sites had undergone purifying selection in all other subtypes. Also, amino acid sites within subtypes A and K that had undergone purifying selection were observed, while these sites had undergone positive selection in all other subtypes. The presence of such sites indicates heterogeneity of selective pressures within HIV-1 group M subtype evolution that may account for the various levels of fitness of the subtypes.

Amino Acid Sequence↗

PubMed2005

Molecular evolution of growth hormone gene family in old world monkeys and hominoids.

Growth hormone is a classic molecule in the study of the molecular clock hypothesis as it exhibits a relatively constant rate of evolution in most mammalian orders except primates and artiodactyls, where dramatically enhanced rate of evolution (25-50-fold) has been reported. The rapid evolution of primate growth hormone occurred after the divergence of tarsiers and simians, but before the separation of old world monkeys (OWM) from new world monkeys (NWM). Interestingly, this event of rapid sequence evolution coincided with multiple duplications of the growth hormone gene, suggesting gene duplication as a possible cause of the accelerated sequence evolution. Here we determined 21 different GH-like sequences from four species of OWM and hominoids. Combining with published sequences from OWM and hominoids, our analysis demonstrates that multiple gene duplications and several gene conversion events both occurred in the evolutionary history of this gene family in OWM/hominoids. The episode of recent duplications of CSH-like genes in gibbon is accompanied with rapid sequence evolution likely resulting from relaxation of purifying selection. GHN genes in both hominoids and OWM are under strong purifying selection. In contrast, CSH genes in both lineages are probably not. GHV genes in OWM and hominoids evolved at different evolutionary rates and underwent different selective constraints. Our results disclosed the complex history of the primate growth hormone gene family and raised intriguing questions on the consequences of these evolutionary events.

Animals↗