Showing papers on "Genetic hitchhiking published in 2006"

The Origins of Eukaryotic Gene Structure

Abstract: Most of the phenotypic diversity that we perceive in the natural world is directly attributable to the peculiar structure of the eukaryotic gene, which harbors numerous embellishments relative to the situation in prokaryotes. The most profound changes include introns that must be spliced out of precursor mRNAs, transcribed but untranslated leader and trailer sequences (untranslated regions), modular regulatory elements that drive patterns of gene expression, and expansive intergenic regions that harbor additional diffuse control mechanisms. Explaining the origins of these features is difficult because they each impose an intrinsic disadvantage by increasing the genic mutation rate to defective alleles. To address these issues, a general hypothesis for the emergence of eukaryotic gene structure is provided here. Extensive information on absolute population sizes, recombination rates, and mutation rates strongly supports the view that eukaryotes have reduced genetic effective population sizes relative to prokaryotes, with especially extreme reductions being the rule in multicellular lineages. The resultant increase in the power of random genetic drift appears to be sufficient to overwhelm the weak mutational disadvantages associated with most novel aspects of the eukaryotic gene, supporting the idea that most such changes are simple outcomes of semi-neutral processes rather than direct products of natural selection. However, by establishing an essentially permanent change in the population-genetic environment permissive to the genome-wide repatterning of gene structure, the eukaryotic condition also promoted a reliable resource from which natural selection could secondarily build novel forms of organismal complexity. Under this hypothesis, arguments based on molecular, cellular, and/or physiological constraints are insufficient to explain the disparities in gene, genomic, and phenotypic complexity between prokaryotes and eukaryotes.

The hitchhiking effect on linkage disequilibrium between linked neutral loci.

Abstract: We analyzed a three-locus model of genetic hitchhiking with one locus experiencing positive directional selection and two partially linked neutral loci. Following the original hitchhiking approach by Maynard Smith and Haigh, our analysis is purely deterministic. In the first half of the selected phase after a favored mutation has entered the population, hitchhiking may lead to a strong increase of linkage disequilibrium (LD) between the two neutral sites if both are 0.3s), the decay rate of LD approaches that of neutrality. Averaging over a uniform distribution of initial gamete frequencies shows that the expected LD at the end of the hitchhiking phase is driven toward zero, while the variance is increased when the selected site is well outside the two neutral sites. When the direction of LD is polarized with respect to the more common allele at each neutral site, hitchhiking creates more positive than negative linkage disequilibrium. Thus, hitchhiking may have a distinctively patterned LD-reducing effect, in particular near the target of selection.

The Hill–Robertson Effect and the Evolution of Recombination

Abstract: In finite populations, genetic drift generates interference between selected loci, causing advantageous alleles to be found more often on different chromosomes than on the same chromosome, which reduces the rate of adaptation. This “Hill–Robertson effect” generates indirect selection to increase recombination rates. We present a new method to quantify the strength of this selection. Our model represents a new beneficial allele (A) entering a population as a single copy, while another beneficial allele (B) is sweeping at another locus. A third locus affects the recombination rate between selected loci. Using a branching process model, we calculate the probability distribution of the number of copies of A on the different genetic backgrounds, after it is established but while it is still rare. Then, we use a deterministic model to express the change in frequency of the recombination modifier, due to hitchhiking, as A goes to fixation. We show that this method can give good estimates of selection for recombination. Moreover, it shows that recombination is selected through two different effects: it increases the fixation probability of new alleles, and it accelerates selective sweeps. The relative importance of these two effects depends on the relative times of occurrence of the beneficial alleles.

Directional Positive Selection on an Allele of Arbitrary Dominance

Abstract: Most models of positive directional selection assume codominance of the beneficial allele. We examine the importance of this assumption by implementing a coalescent model of positive directional selection with arbitrary dominance. We find that, for a given mean fixation time, a beneficial allele has a much weaker effect on diversity at linked neutral sites when the allele is recessive.

Allele Frequency Distribution Under Recurrent Selective Sweeps

Abstract: The allele frequency of a neutral variant in a population is pushed either upward or downward by directional selection on a linked beneficial mutation (“selective sweeps”). DNA sequences sampled after the fixation of the beneficial allele thus contain an excess of rare neutral alleles. This study investigates the allele frequency distribution under selective sweep models using analytic approximation and simulation. First, given a single selective sweep at a fixed time, I derive an expression for the sampling probabilities of neutral mutants. This solution can be used to estimate the time of the fixation of a beneficial allele from sequence data. Next, I obtain an approximation to mean allele frequencies under recurrent selective sweeps. Under recurrent sweeps, the frequency spectrum is skewed toward rare alleles. However, the excess of high-frequency derived alleles, previously shown to be a signature of single selective sweeps, disappears with recurrent sweeps. It is shown that, using this approximation and multilocus polymorphism data, genomewide parameters of directional selection can be estimated.

An approximate sampling formula under genetic hitchhiking

Abstract: For a genetic locus carrying a strongly beneficial allele which has just fixed in a large population, we study the ancestry at a linked neutral locus. During this “selective sweep” the linkage between the two loci is broken up by recombination and the ancestry at the neutral locus is modeled by a structured coalescent in a random background. For large selection coefficients α and under an appropriate scaling of the recombination rate, we derive a sampling formula with an order of accuracy of $\mathcal{O}((\log \alpha)^{-2})$ in probability. In particular we see that, with this order of accuracy, in a sample of fixed size there are at most two nonsingleton families of individuals which are identical by descent at the neutral locus from the beginning of the sweep. This refines a formula going back to the work of Maynard Smith and Haigh, and complements recent work of Schweinsberg and Durrett on selective sweeps in the Moran model.

Testing for Effects of Recombination Rate on Nucleotide Diversity in Natural Populations of Arabidopsis lyrata

Abstract: We investigated DNA sequence diversity for loci on chromosomes 1 and 2 in six natural populations of Arabidopsis lyrata and tested for the role of natural selection in structuring genomewide patterns of variability, specifically examining the effects of recombination rate on levels of silent polymorphism. In contrast with theoretical predictions from models of genetic hitchhiking, maximum-likelihood-based analyses of diversity and divergence do not suggest reduction of diversity in the region of suppressed recombination near the centromere of chromosome 1, except in a single population from Russia, in which the pericentromeric region may have undergone a local selective sweep or demographic process that reduced variability. We discuss various possibilities that might explain why nucleotide diversity in most A. lyrata populations is not related to recombination rate, including genic recombination hotspots, and low gene density in the low recombination rate region.

Evolutionary history of a mosquito endosymbiont revealed through mitochondrial hitchhiking

Abstract: Due to cytoplasmic inheritance, spread of maternally inherited Wolbachia symbionts can result in reduction of mitochondrial variation in populations. We examined sequence diversity of the mitochond...

Positive Selection Can Create False Hotspots of Recombination

Abstract: 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.

Variation in synonymous codon use and DNA polymorphism within the Drosophila genome

Abstract: A strong negative correlation between the rate of amino-acid substitution and codon usage bias in Drosophila has been attributed to interference between positive selection at nonsynonymous sites and weak selection on codon usage. To further explore this possibility we have investigated polymorphism and divergence at three kinds of sites: synonymous, nonsynonymous and intronic in relation to codon bias in D. melanogaster and D. simulans. We confirmed that protein evolution is one of the main explicative parameters for interlocus codon bias variation (r2~ 40%). However, intron or synonymous diversities, which could have been expected to be good indicators of local interference [here defined as the additional increase of drift due to selection on tightly linked sites, also called `genetic draft? by Gillespie (2000)] did not covary significantly with codon bias or with protein evolution. Concurrently, levels of polymorphism were reduced in regions of low recombination rates whereas codon bias was not. Finally, while nonsynonymous diversities were very well correlated between species, neither synonymous nor intron diversities observed in D. melanogaster were correlated with those observed in D. simulans. All together, our results suggest that the selective constraint on the protein is a stable component of gene evolution while local interference is not. The pattern of variation in genetic draft along the genome therefore seems to be instable through evolutionary times and should therefore be considered as a minor determinant of codon bias variance. We argue that selective constraints for optimal codon usage are likely to be correlated with selective constraints on the protein, both between codons within a gene, as previously suggested, and also between genes within a genome.

Approximate Genealogies Under Genetic Hitchhiking

Abstract: The rapid fixation of an advantageous allele leads to a reduction in linked neutral variation around the target of selection. The genealogy at a neutral locus in such a selective sweep can be simulated by first generating a random path of the advantageous allele's frequency and then a structured coalescent in this background. Usually the frequency path is approximated by a logistic growth curve. We discuss an alternative method that approximates the genealogy by a random binary splitting tree, a so-called Yule tree that does not require first constructing a frequency path. Compared to the coalescent in a logistic background, this method gives a slightly better approximation for identity by descent during the selective phase and a much better approximation for the number of lineages that stem from the founder of the selective sweep. In applications such as the approximation of the distribution of Tajima's D, the two approximation methods perform equally well. For relevant parameter ranges, the Yule approximation is faster.

The Influence of Hitchhiking and Deleterious Mutation Upon Asexual Mutation Rates

Abstract: The question of how natural selection affects asexual mutation rates has been considered since the 1930s, yet our understanding continues to deepen. The distribution of mutation rates observed in natural bacteria remains unexplained. It is well known that environmental constancy can favor minimal mutation rates. In contrast, environmental fluctuation (e.g., at period T) can create indirect selective pressure for stronger mutators: genes modifying mutation rate may “hitchhike” to greater frequency along with environmentally favored mutations they produce. This article extends a well-known model of Leigh to consider fitness genes with multiple mutable sites (call the number of such sites α). The phenotypic effect of such a gene is enabled if all sites are in a certain state and disabled otherwise. The effects of multiple deleterious loci are also included (call the number of such loci γ). The analysis calculates the indirect selective effects experienced by a gene inducing various mutation rates for given values of α, γ, and T. Finite-population simulations validate these results and let us examine the interaction of drift with hitchhiking selection. We close by commenting on the importance of other factors, such as spatiotemporal variation, and on the origin of variation in mutation rates.

Increased Nucleotide Diversity with Transient Y Linkage in Drosophila americana

Abstract: Recombination shapes nucleotide variation within genomes. Patterns are thought to arise from the local recombination landscape, influencing the degree to which neutral variation experiences hitchhiking with selected variation. This study examines DNA polymorphism along Chromosome 4 (element B) of Drosophila americana to identify effects of hitchhiking arising as a consequence of Y-linked transmission. A centromeric fusion between the X and 4th chromosomes segregates in natural populations of D. americana. Frequency of the X-4 fusion exhibits a strong positive correlation with latitude, which has explicit consequences for unfused 4th chromosomes. Unfused Chromosome 4 exists as a non-recombining Y chromosome or as an autosome proportional to the frequency of the X-4 fusion. Furthermore, Y linkage along the unfused 4 is disrupted as a function of the rate of recombination with the centromere. Inter-population and intra-chromosomal patterns of nucleotide diversity were assayed using six regions distributed along unfused 4th chromosomes derived from populations with different frequencies of the X-4 fusion. No difference in overall level of nucleotide diversity was detected among populations, yet variation along the chromosome exhibits a distinct pattern in relation to the X-4 fusion. Sequence diversity is inflated at loci experiencing the strongest Y linkage. These findings are inconsistent with the expected reduction in nucleotide diversity resulting from hitchhiking due to background selection or selective sweeps. In contrast, excessive polymorphism is accruing in association with transient Y linkage, and furthermore, hitchhiking with sexually antagonistic alleles is potentially responsible.

The hitchhiking effect of an autosomal meiotic drive gene.

Abstract: Transmission-ratio distortion is a departure from a 1:1 segregation of alleles in the gametes of a heterozygous individual. The so-called driving allele is strongly selected regardless of its effect on the fitness of the carrying individual. It may then have an important impact on neutral polymorphism due to the genetic hitchhiking effect. We study this hitchhiking effect in the case of true meiotic drive in autosomes and show that it is more dependent on the recombination rate than in the classical case of a gene positively selected at the organism level.

Postcopulatory Sexual Selection Reduces Genetic Diversity in Experimental Populations of Caenorhabditis elegans

Abstract: Postcopulatory sexual selection affects the evolution of numerous features ranging from mating behavior to seminal fluid toxicity to the size of gametes. In an earlier study of the effect of sperm competition risk on sperm size evolution, experimental populations of the nematode Caenorhabditis elegans were maintained either by outcrossing (sperm competition present) or by selfing (no sperm competition), and after 60 generations, significantly larger sperm had evolved in the outcrossing populations. To determine the effects of this selection on population genetic variation, we assessed genetic diversity in a large number of loci using random amplification of polymorphic DNA-PCR. Nearly 80% of the alleles present in parental strain populations persisted in the 6 experimental populations after the 60 generations and, despite a 2.2-fold difference in expected heterozygosity, the resulting levels of genetic variation were equivalent between the outcrossing and selfing experimental populations. By inference, we conclude that genetic hitchhiking due to sexual selection in the experimental populations dramatically reduced genetic diversity. We use the levels of variation in the selfing populations as a control for the effects of drift, and estimate the strength of sexual selection to be strong in obligatorily outcrossing populations. Although sequential hermaphrodites like C. elegans probably experience little sexual selection in nature, these data suggest that sexual selection can profoundly affect diversity in outcrossing taxa.

A Systematic Assessment of Signatures of Positive Selection Events in Natural Populations of the House Mouse

Abstract: The frequency and the structure of positive selection events in natural populations are of central importance, but one of the least known variables in evolutionary biology. The aim of this study is to investigate these basic parameters in a population based approach. Positive selection events leave population genetical signatures (selective sweeps) behind, which can be systematically identified with molecular studies. Positive selection can lead to the fixation of a favorable mutation in a population. Due to an effect called hitchhiking, variability in the neutral flanking regions which are physically linked to the target of selection is lost. This footprint of reduced neutral variability can be employed to systematically screen for positively selected (adaptive) mutations and allows to estimate their frequency in a given population. Differences in recombination rates along the chromosomes can influence the evolution of neutral loci via hitchhiking effects even on a large time scale, which would influence the results. Generally, these effects should be stronger in regions of low recombination than in regions of high recombination. The detailed information on physical and genetic maps in the house mouse allows now to assess the correlation between neutral variability and recombination rates at given chromosomal regions. I have tested microsatellite loci from chromosomal regions which show differences in recombination rates and found no evidence for a correlation between microsatellite variability and recombination rates in samples from five wild mice populations (Mus musculus musculus and M. m. domesticus). This suggests that the high average mutation rate of microsatellites in mammals counter balances the effects of long range hitchhiking in the mouse genome. Approaches, in which the variability of neutral markers is used to identify regions which have recently been under positive selection, is termed hitchhiking mapping. Since higher eukaryotic genomes may contain about 40,000 selectable loci and the detection of polymorphic variants requires testing of multiple individuals (at least 20) for several populations, a complete genome scan would require millions of genotypes to be determined. I present here a pooling strategy that allows to reduce the number of genotyping reactions significantly. The presented high throughput routine enabled me to investigate almost 1,000 microsatellite loci in different populations of the house mouse. Among the composite patterns that are obtained in this way, it is possible to visually select those with population specifical reduced variability. In a second step, these candidates were then re-typed in individuals of a carefully chosen population background and statistically tested for significance. A detailed analysis of the candidate loci identified by a single comparison yield results on the frequency of selective sweeps, the strength of selection acting in natural populations and the origin of selected variants. The two investigated populations of the house mouse (M. m. domesticus) have split upon arrival in Middle Europe about 3,000 years ago. The massive invasion of house mice into Europe is well documented based on fossil records. Strong independent subsequent bottlenecks can be ruled out because of a comparable high genome wide variability in both populations. Thus, complex demographic influences on the results can be excluded. Identified candidate regions between the two focal populations were further characterized by genotyping additional microsatellites in the flanking regions of the identified candidates. The significant deviation of the candidate regions from the neutral state is supported by several statistical tests. Based on these results, I find that there was at least one positive selection event per 100 generations in each lineage. Since none of the detected sweep valleys is broad, on average they are about 50 kb, I conclude that positive selection in general is driven by alleles providing weak beneficial impact. Estimated selection coefficients vary between 0.0007 and 0.021. Furthermore, it seems that beneficial variants are generally taken from the standing variation and that positive selection is a continuously acting background effect in all population.

Stationary Allele Frequency Distributions

Abstract: Forces that determine the allele frequencies in natural populations include genetic drift, natural selection, migration and mutation. A balance of opposing forces can, in some cases, cause allele frequencies to approach a stationary distribution over time. The form of this distribution is not influenced by initial allele frequencies, but instead is determined by the relative magnitudes of different evolutionary forces. Statistical distributions are presented for the stationary allele frequencies under several simple population genetic models (including the k alleles symmetrical mutation model and the Wright island model of migration). In addition, the sampling distribution of allele counts under these models are described. The latter is useful when using genetic marker data to estimate population parameters. A population is at genetic equilibrium if evolutionary forces have persisted long enough for a population to have reached the stationary distribution, this is not often the case in nature. Key Concepts: If evolutionary forces such as natural selection, genetic drift and migration remain constant allele frequencies may reach to a stationary distribution. Because evolutionary forces are often changing on a relatively short time-scale the allele frequencies in many populations will not be at equilibrium. Statistics based on parameters of stationary distributions may provide a useful summary of the genetic variation in populations that are not at equilibrium. Simulation methods can be used to study allele frequency distributions for more complex models. Modern approaches focus on nonstationary sampling distributions derived using the coalescent process model. Keywords: probability distribution; Fisher-Wright model; genetic drift; migration; mutation; sampling distribution

Mutational Change in Evolution

Abstract: Evolution is the process of change in the genetic make-up of populations. Two evolutionary forces are known to cause changes in gene frequencies with time: selection and random genetic drift. Keywords: mutation; selection; drift; population; substitution

Hitchhiking Effect Mapping: A New Approach for Discovering

Abstract: Beside natural selection, today's cultivated crops have experienced two types of strong artificial selections: domestication and modern breeding. Domestication has led to a giant genetic structure differentiation between cultivars and their wild relatives, and modern breeding has created further genetic structure differentiation between the modern varieties and the landraces. In a genome, genetic diversity at a locus experienced strong selection is significantly lower than that at other loci non-experienced selection and diversities in the flanking regions also declines. This phenomenon is called the hitchhiking effect or genetic selection sweep. The genomic regions with selection sweep could be detected through scanning a number of released varieties or natural populations with molecular markers. Thereafter, agronomic important traits linked with these regions could be detected using Marker/Trait association analysis. Fine scanning of these genomic regions would help to determine the sizes of these