Showing papers on "Genetic hitchhiking published in 1993"

The effect of deleterious mutations on neutral molecular variation.

Abstract: Selection against deleterious alleles maintained by mutation may cause a reduction in the amount of genetic variability at linked neutral sites. This is because a new neutral variant can only remain in a large population for a long period of time if it is maintained in gametes that are free of deleterious alleles, and hence are not destined for rapid elimination from the population by selection. Approximate formulas are derived for the reduction below classical neutral values resulting from such background selection against deleterious mutations, for the mean times to fixation and loss of new mutations, nucleotide site diversity, and number of segregating sites. These formulas apply to random-mating populations with no genetic recombination, and to populations reproducing exclusively asexually or by self-fertilization. For a given selection regime and mating system, the reduction is an exponential function of the total mutation rate to deleterious mutations for the section of the genome involved. Simulations show that the effect decreases rapidly with increasing recombination frequency or rate of outcrossing. The mean time to loss of new neutral mutations and the total number of segregating neutral sites are less sensitive to background selection than the other statistics, unless the population size is of the order of a hundred thousand or more. The stationary distribution of allele frequencies at the neutral sites is correspondingly skewed in favor of rare alleles, compared with the classical neutral result. Observed reductions in molecular variation in low recombination genomic regions of sufficiently large size, for instance in the centromere-proximal regions of Drosophila autosomes or in highly selfing plant populations, may be partly due to background selection against deleterious mutations.

Reduced natural selection associated with low recombination in Drosophila melanogaster.

Abstract: Synonymous codons are not used equally in many organisms, and the extent of codon bias varies among loci. Earlier studies have suggested that more highly expressed loci in Drosophila melanogaster are more biased, consistent with findings from several prokaryotes and unicellular eukaryotes that codon bias is partly due to natural selection for translational efficiency. We link this model of varying selection intensity to the population-genetics prediction that the effectiveness of natural selection is decreased under reduced recombination. In analyses of 385 D. melanogaster loci, we find that codon bias is reduced in regions of low recombination (i.e., near centromeres and telomeres and on the fourth chromosome). The effect does not appear to be a linear function of recombination rate; rather, it seems limited to regions with the very lowest levels of recombination. The large majority of the genome apparently experiences recombination at a sufficiently high rate for effective natural selection against suboptimal codons. These findings support models of the Hill-Robertson effect and genetic hitchhiking and are largely consistent with multiple reports of low levels of DNA sequence variation in regions of low recombination.

Analysis of a genetic hitchhiking model, and its application to DNA polymorphism data from Drosophila melanogaster.

Abstract: Begun and Aquadro have demonstrated that levels of nucleotide variation correlate with recombination rate among 20 gene regions from across the genome of Drosophila melanogaster. It has been suggested that this correlation results from genetic hitchhiking associated with the fixation of strongly selected mutants. The hitchhiking process can be described as a series of two-step events. The first step consists of a strongly selected substitution wiping out linked variation in a population; this is followed by a recovery period in which polymorphism can build up via neutral mutations and random genetic drift. Genetic hitchhiking has previously been modeled as a steady-state process driven by recurring selected substitutions. We show here that the characteristic parameter of this steady-state model is alpha v, the product of selection intensity (alpha = 2Ns) and the frequency of beneficial mutations v (where N is population size and s is the selective advantage of the favored allele). We also demonstrate that the steady-state model describes the hitchhiking process adequately, unless the recombination rate is very low. To estimate alpha v, we use the data of DNA sequence variation from 17 D. melanogaster loci from regions of intermediate to high recombination rates. We find that alpha v is likely to be > 1.3 x 10(-8). Additional data are needed to estimate this parameter more precisely. The estimation of alpha v is important, as this parameter determines the shape of the frequency distribution of strongly selected substitutions.

DNA sequence variation at the period locus within and among species of the Drosophila melanogaster complex.

Abstract: A 1.9-kilobase region of the period locus was sequenced in six individuals of Drosophila melanogaster and from six individuals of each of three sibling species: Drosophila simulans, Drosophila sechellia and Drosophila mauritiana. Extensive genealogical analysis of 174 polymorphic sites reveals a complex history. It appears that D. simulans, as a large population still segregating very old lineages, gave rise to the island species D. mauritiana and D. sechellia. Rather than considering these speciation events as having produced “sister” taxa, it seems more appropriate to consider D. simulans a parent species to D. sechellia and D. mauritiana. The order, in time, of these two phylogenetic events remains unclear. D. mauritiana supports a large number of polymorphisms, many of which are shared with D. simulans, and so appears to have begun and persisted as a large population. In contrast, D. sechellia has very little variation and seems to have experienced a severe population bottleneck. Alternatively, the low variation in D. sechellia could be due to recent directional selection and genetic hitchhiking at or near the per locus.

Statistical analysis of DNA polymorphism.

Abstract: A large amount of genetic variation can be maintained in natural populations. In order to understand the mechanism maintaining genetic variation, we must first estimate the amount of genetic variation. There are two measures for estimating the amount of DNA polymorphism, i.e., the average number of pairwise nucleotide differences and the number of segregating sites among a sample of DNA sequences. Using these two measures, we can test the neutral mutation-random drift hypothesis (the neutral theory). The expectation of the amount of DNA polymorphism has been studied under several models, including population subdivision, change in population size, and natural selection. When a population is subdivided, a large amount of DNA polymorphism can be maintained in the population if the migration rates among subpopulations are small. In this case the amount of DNA polymorphism in the subpopulation with lower migration rate is expected to be smaller than that of higher migration rate. When the population size changes, the number of segregating sites changes more rapidly than does the average number of nucleotide differences. When purifying selection is operating, the number of segregating sites is more strongly affected by the existence of deleterious mutants than is the average number of nucleotide differences. On the other hand, when balancing selection is operating, the effect of the selection on the average number of nucleotide differences is larger than that on the number of segregating sites. A mutant under natural selection affects the amount of DNA polymorphism at linked sites (hitchhiking effect). DNA sequences are not random sequences and there may be conservative and variable regions in them. A statistical method for determining the window size and for finding nonrandom regions in the sequence is also presented.

Lack of correlation between interspecific divergence and intraspecific polymorphism at the suppressor of forked region in Drosophila melanogaster and Drosophila simulans.

Abstract: Levels of DNA sequence polymorphism at the suppressor of forked [su(f)] region in natural populations of Drosophila melanogaster and Drosophila simulans are estimated by restriction map analysis. su(f) is located at the base of the euchromatic portion of the X chromosome where the level of crossing-over per physical length is extremely low. In a survey of 55 alleles from three natural populations of D. melanogaster, only 2 restriction sites of 27 hexanucleotide and 108 tetranucleotide restriction sites scored are polymorphic. Among 103 alleles from three natural populations of D. simulans, just one polymorphic restriction site is found in 109 tetranucleotide-recognizing restriction sites scored. The few polymorphisms in these surveys yield estimates of per site heterozygosities (0.00, 0.0002, and 0.0005, respectively) at least a factor of 10 less than the average observed at loci located in regions of the genome with normal levels of crossing-over. Because under a broad category of models of molecular evolution (including the neutral theory) a correlation between levels of polymorphism and interspecific divergence is expected, the DNA sequence divergence is examined for the su(f) region. Contrary to the predicted correlation, the estimated divergence (0.12 substitution per silent site) is, in fact, greater than that observed at loci in regions of normal crossing-over. According to an alternative hypothesis (hitchhiking effect model) intraspecific polymorphism is swept out of the population in regions of the genome closely linked to rare but selectively favored variants as they quickly go to fixation; the rate of divergence is, however, unaffected by these rare hitchhiking events. Thus, the observed paucity of polymorphism and lack of correlation with divergence are in accord with the theory of the hitchhiking effect and several recent reports of polymorphism and divergence in other genomic regions with reduced crossing-over per physical length.

On the probability of loss of new mutations in the presence of linkage disequilibrium.

Abstract: A new selectively neutral mutation occurs in a multilocus genetic background that has achieved a stable equilibrium at which there is a linkage disequilibrium. Perturbation techniques are applied to an extension of the branching process formulation of Fisher in order to address the question of extinction probabilities. We show that under appropriate conditions the probability of extinction of the new mutant is increased by the existence of linkage disequilibrium in the genetic background.