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Results for “selective sweeps”

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PubMed2002

Diversifying selection of the tumor-growth promoter angiogenin in primate evolution.

Diversifying selection drives the rapid differentiation of gene sequences and is one of the main forces behind adaptive evolution. Most genes known to be shaped by diversifying selection are those involved in host-pathogen or male-female interactions characterized as molecular "arms races." Here we report the unexpected detection of diversifying selection in the evolution of a tumor-growth promoter, angiogenin (ANG). A comparison among 11 primate species demonstrates that ANG has a significantly higher rate of nucleotide substitution at nonsynonymous sites than at synonymous sites, a hallmark of positive selection acting at the molecular level. Furthermore, we observed significant charge diversity at the molecular surface, suggesting the presence of selective pressures in the microenvironment of ANG, including its binding molecules. A population survey of ANG in chimpanzees, however, reveals no polymorphism, which may have resulted from a recent selective sweep of a charge-altering substitution in chimpanzee evolution. Functional assays of recombinant ANGs from the human and owl monkey indicate that primate ANGs retain angiogenic activity despite rapid evolution. Our study, together with findings of similar selection in the primate breast cancer suppressor gene, BRCA1, reveals an intriguing phenomenon of unusual selective pressures on, and adaptive evolution of, cancer-related genes in primate evolution.

Amino Acid Sequence↗
PubMed2005

Maximum-likelihood methods for detecting recent positive selection and localizing the selected site in the genome.

Two maximum-likelihood methods are proposed for detecting recent, strongly positive selection and for localizing the target of selection along a recombining chromosome. The methods utilize the compact mutation frequency spectrum at multiple neutral loci that are partially linked to the selected site. Using simulated data, we show that the power of the tests lies between 80 and 98% in most cases, and the false positive rate could be as low as approximately 10% when the number of sampled marker loci is sufficiently large (> or = 20). The confidence interval around the estimated position of selection is reasonably narrow. The methods are applied to X chromosome data of Drosophila melanogaster from a European and an African population. Evidence of selection was found for both populations (including a selective sweep that was shared between both populations).

Africa↗
PubMed2003

The early stages of duplicate gene evolution.

Gene duplications are one of the primary driving forces in the evolution of genomes and genetic systems. Gene duplicates account for 8-20% of the genes in eukaryotic genomes, and the rates of gene duplication are estimated at between 0.2% and 2% per gene per million years. Duplicate genes are believed to be a major mechanism for the establishment of new gene functions and the generation of evolutionary novelty, yet very little is known about the early stages of the evolution of duplicated gene pairs. It is unclear, for example, to what extent selection, rather than neutral genetic drift, drives the fixation and early evolution of duplicate loci. Analysis of recently duplicated genes in the Arabidopsis thaliana genome reveals significantly reduced species-wide levels of nucleotide polymorphisms in the progenitor and/or duplicate gene copies, suggesting that selective sweeps accompany the initial stages of the evolution of these duplicated gene pairs. Our results support recent theoretical work that indicates that fates of duplicate gene pairs may be determined in the initial phases of duplicate gene evolution and that positive selection plays a prominent role in the evolutionary dynamics of the very early histories of duplicate nuclear genes.

Arabidopsis↗
PubMed1999

Population dynamics of HIV-1 inferred from gene sequences.

A method for the estimation of population dynamic history from sequence data is described and used to investigate the past population dynamics of HIV-1 subtypes A and B. Using both gag and env gene alignments the effective population size of each subtype is estimated and found to be surprisingly small. This may be a result of the selective sweep of mutations through the population, or may indicate an important role of genetic drift in the fixation of mutations. The implications of these results for the spread of drug-resistant mutations and transmission dynamics, and also the roles of selection and recombination in shaping HIV-1 genetic diversity, are discussed. A larger estimated effective population size for subtype A may be the result of differences in time of origin, transmission dynamics, and/or population structure. To investigate the importance of population structure a model of population subdivision was fitted to each subtype, although the improvement in likelihood was found to be nonsignificant.

Genes, Viral↗
PubMed1996

High nucleotide sequence variation in a region of low recombination in Drosophila simulans is consistent with the background selection model.

We surveyed nucleotide sequence variation at glucose dehydrogenase (Gld), in a region of low recombination on chromosome 3R, from a population sample of Drosophila simulans. The levels of nucleotide variation were surprisingly high. There was no departure from the expectation of a neutral model for the level of polymorphism, indicating no evidence of a selective sweep in this region. There was a significant deficiency of singleton polymorphisms according to the Fu and Li test, although Tajima and Hudson, Kreitman, and Aguade (HKA) tests do not provide evidence of a significant elevation of variation due to balancing selection. Genetic map data for the D. simulans third chromosome were used to calculate expected values of pi for Gld under a current model of background selection, varying the values for the parameter sh (selection coefficient against deleterious mutations). We show that the recombinational landscape of D. simulans is sufficiently different from that of D. melanogaster that we expect higher variation under the background selection model, even when effective population sizes are assumed to be equal. The data for Gld were tested against the predictions using computer simulations of the distribution of the number of segregating sites conditioned on pi. Background selection alone can explain our observations as long as sh is larger than 0.005 and species-level effective population size is assumed to be several-fold larger than in D. melanogaster. Alternatively, the deleterious mutation rate may be smaller in D. simulans, or balancing selection may be acting nearby, thereby reducing the effect of background selection.

Animals↗
PubMed2004

Reduced variation on the chicken Z chromosome.

Understanding the population genetic factors that shape genome variability is pivotal to the design and interpretation of studies using large-scale polymorphism data. We analyzed patterns of polymorphism and divergence at Z-linked and autosomal loci in the domestic chicken (Gallus gallus) to study the influence of mutation, effective population size, selection, and demography on levels of genetic diversity. A total of 14 autosomal introns (8316 bp) and 13 Z-linked introns (6856 bp) were sequenced in 50 chicken chromosomes from 10 highly divergent breeds. Genetic variation was significantly lower at Z-linked than at autosomal loci, with one segregating site every 39 bp at autosomal loci (theta(W) = 5.8 +/- 0.8 x 10(-3)) and one every 156 bp on the Z chromosome (theta(W) = 1.4 +/- 0.4 x 10(-3)). This difference may in part be due to a low male effective population size arising from skewed reproductive success among males, evident both in the wild ancestor-the red jungle fowl-and in poultry breeding. However, this effect cannot entirely explain the observed three- to fourfold reduction in Z chromosome diversity. Selection, in particular selective sweeps, may therefore have had an impact on reducing variation on the Z chromosome, a hypothesis supported by the observation of heterogeneity in diversity levels among loci on the Z chromosome and the lower recombination rate on Z than on autosomes. Selection on sex-linked genes may be particularly important in organisms with female heterogamety since the heritability of sex-linked sexually antagonistic alleles advantageous to males is improved when fathers pass a Z chromosome to their sons.

Alleles↗
PubMed2024

Repeated evolution on oceanic islands: comparative genomics reveals species-specific processes in birds.

Understanding the interplay between genetic drift, natural selection, gene flow, and demographic history in driving phenotypic and genomic differentiation of insular populations can help us gain insight into the speciation process. Comparing patterns across different insular taxa subjected to similar selective pressures upon colonizing oceanic islands provides the opportunity to study repeated evolution and identify shared patterns in their genomic landscapes of differentiation. We selected four species of passerine birds (Common Chaffinch Fringilla coelebs/canariensis, Red-billed Chough Pyrrhocorax pyrrhocorax, House Finch  Haemorhous mexicanus and Dark-eyed/island Junco Junco hyemalis/insularis) that have both mainland and insular populations. Changes in body size between island and mainland populations were consistent with the island rule. For each species, we sequenced whole genomes from mainland and insular individuals to infer their demographic history, characterize their genomic differentiation, and identify the factors shaping them. We estimated the relative (Fst) and absolute (dxy) differentiation, nucleotide diversity (π), Tajima's D, gene density and recombination rate. We also searched for selective sweeps and chromosomal inversions along the genome. All species shared a marked reduction in effective population size (Ne) upon island colonization. We found diverse patterns of differentiated genomic regions relative to the genome average in all four species, suggesting the role of selection in island-mainland differentiation, yet the lack of congruence in the location of these regions indicates that each species evolved differently in insular environments. Our results suggest that the genomic mechanisms involved in the divergence upon island colonization-such as chromosomal inversions, and historical factors like recurrent selection-differ in each species, despite the highly conserved structure of avian genomes and the similar selective factors involved. These differences are likely influenced by factors such as genetic drift, the polygenic nature of fitness traits and the action of case-specific selective pressures.

Animals↗
PubMed1994

Unraveling selection in the mitochondrial genome of Drosophila.

We examine mitochondrial DNA variation at the cytochrome b locus within and between three species of Drosophila to determine whether patterns of variation conform to the predictions of neutral molecular evolution. The entire 1137-bp cytochrome b locus was sequenced in 16 lines of Drosophila melanogaster, 18 lines of Drosophila simulans and 13 lines of Drosophila yakuba. Patterns of variation depart from neutrality by several test criteria. Analysis of the evolutionary clock hypothesis shows unequal rates of change along D. simulans lineages. A comparison within and between species of the ratio of amino acid replacement change to synonymous change reveals a relative excess of amino acid replacement polymorphism compared to the neutral prediction, suggestive of slightly deleterious or diversifying selection. There is evidence for excess homozygosity in our world wide sample of D. melanogaster and D. simulans alleles, as well as a reduction in the number of segregating sites in D. simulans, indicative of selective sweeps. Furthermore, a test of neutrality for codon usage shows the direction of mutations at third positions differs among different topological regions of the gene tree. The analyses indicate that molecular variation and evolution of mtDNA are governed by many of the same selective forces that have been shown to govern nuclear genome evolution and suggest caution be taken in the use of mtDNA as a "neutral" molecular marker.

Animals↗
PubMed2004

Detecting the footprint of positive selection in a european population of Drosophila melanogaster: multilocus pattern of variation and distance to coding regions.

The effects on nucleotide variation of adaptations to temperate habitats and of the possible bottleneck associated with the origin of European populations of Drosophila melanogaster should be detectable in DNA sequences given the short time elapsed relative to the species population size. We surveyed nucleotide variation in 109 fragments distributed across the X chromosome in a European population of D. melanogaster to detect the footprint of positive selection. Fragments were located primarily in large noncoding regions. Multilocus tests based on Tajima's D statistic revealed a significant departure from neutral expectations in a stationary panmictic population, with an important contribution from both positive and negative D values. A positive relationship between Tajima's D values and distance to coding region was detected, with a comparative excess of significantly negative D values in the subset of fragments closer to coding regions. Also, there was a significant heterogeneity in the polymorphism to divergence ratio, with 12 fragments contributing 42% to the test statistic. Moreover, these fragments were comparatively closer to coding regions. These findings would imply positive selection events, and thus selective sweeps, during the species expansion to Europe.

Animals↗
PubMed2005

Positive selection can create false hotspots of recombination.

Simulations of positive directional selection, under parameter values appropriate for approximating human genetic diversity and rates of recombination, reveal that the effects of strong selective sweeps on patterns of linkage disequilibrium (LD) mimic the pattern expected with recombinant hotspots.

Computer Simulation↗
PubMed2002

Testing models of selection and demography in Drosophila simulans.

We analyze patterns of nucleotide variability at 15 X-linked loci and 14 autosomal loci from a North American population of Drosophila simulans. We show that there is significantly more linkage disequilibrium on the X chromosome than on chromosome arm 3R and much more linkage disequilibrium on both chromosomes than expected from estimates of recombination rates, mutation rates, and levels of diversity. To explore what types of evolutionary models might explain this observation, we examine a model of recurrent, nonoverlapping selective sweeps and a model of a recent drastic bottleneck (e.g., founder event) in the demographic history of North American populations of D. simulans. The simple sweep model is not consistent with the observed patterns of linkage disequilibrium nor with the observed frequencies of segregating mutations. Under a restricted range of parameter values, a simple bottleneck model is consistent with multiple facets of the data. While our results do not exclude some influence of selection on X vs. autosome variability levels, they suggest that demography alone may account for patterns of linkage disequilibrium and the frequency spectrum of segregating mutations in this population of D. simulans.

Animals↗
PubMed2004

The role of natural selection in genetic differentiation of worldwide populations of Drosophila ananassae.

The main evolutionary forces leading to genetic differentiation between populations are generally considered to be natural selection, random genetic drift, and limited migration. However, little empirical evidence exists to help explain the extent, mechanism, and relative role of these forces. In this study, we make use of the differential migration behavior of genes located in regions of low and high recombination to infer the role and demographic distribution of natural selection in Drosophila ananassae. Sequence data were obtained from 13 populations, representing almost the entire range of cosmopolitan D. ananassae. The pattern of variation at a 5.1-kb fragment of the furrowed gene, located in a region of very low recombination, appears strikingly different from that of 10 noncoding DNA fragments (introns) in regions of normal to high recombination. Most interestingly, two main haplotypes are present at furrowed, one being fixed in northern populations and the other being fixed or in high frequency in more southern populations. A cline in the frequency of one of these haplotypes occurs in parallel latitudinal transects. Taken together, significant clinal variation and a test against alternative models of natural selection provide evidence of two independent selective sweeps restricted to specific regions of the species range.

Animals↗
PubMed2004

Evolutionary genetics: Mobile DNAs as sources of adaptive change?

Mobile DNAs are potent sources of mutation in wild populations, but seem only rarely to have been used in adaptive evolution. A new study has revealed a mobile DNA insertion in Drosophila simulans that is associated with an apparent selective sweep and an elevation in expression level of an adjacent gene which creates insecticide resistance.

Adaptation, Biological↗
PubMed2003

Unusual pattern of single nucleotide polymorphism at the exuperantia2 locus of Drosophila pseudoobscura.

We have investigated the pattern of DNA sequence variation at the exuperantia2 locus in Drosophila pseudoobscura. This adds to the increasing dataset of genetic variation in D. pseudoobscura, a useful model species for evolutionary genetic studies. The level of silent site nucleotide diversity and the divergence from an outgroup Drosophila miranda are comparable with those for other X-linked loci. One peculiar pattern at the exu2 locus of D. pseudoobscura is a complete linkage disequilibrium between two SNPs, one of which is a replacement site. As a result, there are two distinct haplotype groups in our dataset. Based upon the comparisons with the outgroup sequences from D. miranda and Drosophila persimilis, we show that the newly derived haplotype group has lower diversity than the ancestral haplotype group. The pattern of protein evolution at exu2 shows some deviation from the neutral model. Together, these and other characteristics of the exu2 locus suggest the action of selection on the pattern of SNP variation, consistent with a partial selective sweep associated with the newly derived haplotype.

Animals↗
PubMed2002

Evidence for positive selection and population structure at the human MAO-A gene.

We report the analysis of human nucleotide diversity at a genetic locus known to be involved in a behavioral phenotype, the monoamine oxidase A gene. Sequencing of five regions totaling 18.8 kb and spanning 90 kb of the monoamine oxidase A gene was carried out in 56 male individuals from seven different ethnogeographic groups. We uncovered 41 segregating sites, which formed 46 distinct haplotypes. A permutation test detected substantial population structure in these samples. Consistent with differentiation between populations, linkage disequilibrium is higher than expected under panmixia, with no evidence of a decay with distance. The extent of linkage disequilibrium is not typical of nuclear loci and suggests that the underlying population structure may have been accentuated by a selective sweep that fixed different haplotypes in different populations, or by local adaptation. In support of this suggestion, we find both a reduction in levels of diversity (as measured by a Hudson-Kreitman-Aguade test with the DMD44 locus) and an excess of high frequency-derived variants, as expected after a recent episode of positive selection.

Animals↗
PubMed2000

Joint effects of natural selection and recombination on gene flow between Drosophila ananassae populations.

We estimated DNA sequence variation in a 5.7-kb fragment of the furrowed (fw) gene region within and between four populations of Drosophila ananassae; fw is located in a chromosomal region of very low recombination. We analyzed gene flow between these four populations along a latitudinal transect on the Indian subcontinent: two populations from southern, subtropical areas (Hyderabad, India, and Sri Lanka) and two from more temperate zones in the north (Nepal and Burma). Furthermore, we compared the pattern of differentiation at fw with published data from Om(1D), a gene located in a region of normal recombination. While differentiation at Om(1D) shows an isolation-by-distance effect, at fw the pattern of differentiation is quite different such that the frequencies of single nucleotide polymorphisms are homogenized over extended geographic regions (i.e., among the two populations of the northern species range from Burma and Nepal as well as among the two southern populations from India and Sri Lanka), but strongly differentiated between the northern and southern populations. To examine these differences in the patterns of variation and differentiation between the Om(1D) and fw gene regions, we determine the critical values of our previously proposed test of the background selection hypothesis (henceforth called F(ST) test). Using these results, we show that the pattern of differentiation at fw may be inconsistent with the background selection model. The data depart from this model in a direction that is compatible with the occurrence of recent selective sweeps in the northern as well as southern populations.

Animals↗
PubMed2000

Nucleotide variation at the CHALCONE ISOMERASE locus in Arabidopsis thaliana.

An approximately 1.9-kb region encompassing the CHI gene, which encodes chalcone isomerase, was sequenced in 24 worldwide ecotypes of Arabidopsis thaliana (L.) Heynh. and in 1 ecotype of A. lyrata ssp. petraea. There was no evidence for dimorphism at the CHI region. A minimum of three recombination events was inferred in the history of the sampled ecotypes of the highly selfing A. thaliana. The estimated nucleotide diversity theta(TOTAL) = 0.004, theta(SIL) = 0. 005 was on the lower part of the range of the corresponding estimates for other gene regions. The skewness of the frequency spectrum toward an excess of low-frequency polymorphisms, together with the bell-shaped distribution of pairwise nucleotide differences at CHI, suggests that A. thaliana has recently experienced a rapid population growth. Although this pattern could also be explained by a recent selective sweep at the studied region, results from the other studied loci and from an AFLP survey seem to support the expansion hypothesis. Comparison of silent polymorphism and divergence at the CHI region and at the Adh1 and ChiA revealed in some cases a significant deviation of the direct relationship predicted by the neutral theory, which would be compatible with balancing selection acting at the latter regions.

Arabidopsis↗
PubMed2002

Chromosomal patterns of microsatellite variability contrast sharply in African and non-African populations of Drosophila melanogaster.

Levels of neutral variation are influenced by background selection and hitchhiking. The relative contribution of these evolutionary forces to the distribution of neutral variation is still the subject of ongoing debates. Using 133 microsatellites, we determined levels of variability on X chromosomes and autosomes in African and non-African D. melanogaster populations. In the ancestral African populations microsatellite variability was higher on X chromosomes than on autosomes. In non-African populations X-linked polymorphism is significantly more reduced than autosomal variation. In non-African populations we observed a significant positive correlation between X chromosomal polymorphism and recombination rate. These results are consistent with the interpretation that background selection shapes levels of neutral variability in the ancestral populations, while the pattern in derived populations is determined by multiple selective sweeps during the colonization process. Further research, however, is required to investigate the influence of inversion polymorphisms and unequal sex ratios.

Africa↗