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Selective sweeps in multilocus models of quantitative traits.

ABSTRACT: We study the trajectory of an allele that affects a polygenic trait selected toward a phenotypic optimum. Furthermore, conditioning on this trajectory we analyze the effect of the selected mutation on linked neutral variation. We examine the well-characterized two-locus two-allele model but we also provide results for diallelic models with up to eight loci. First, when the optimum phenotype is that of the double heterozygote in a two-locus model, and there is no dominance or epistasis of effects on the trait, the trajectories of selected mutations rarely reach fixation; instead, a polymorphic equilibrium at both loci is approached. Whether a polymorphic equilibrium is reached (rather than fixation at both loci) depends on the intensity of selection and the relative distances to the optimum of the homozygotes at each locus. Furthermore, if both loci have similar effects on the trait, fixation of an allele at a given locus is less likely when it starts at low frequency and the other locus is polymorphic (with alleles at intermediate frequencies). Weaker selection increases the probability of fixation of the studied allele, as the polymorphic equilibrium is less stable in this case. When we do not require the double heterozygote to be at the optimum we find that the polymorphic equilibrium is more difficult to reach, and fixation becomes more likely. Second, increasing the number of loci decreases the probability of fixation, because adaptation to the optimum is possible by various combinations of alleles. Summaries of the genealogy (height, total length, and imbalance) and of sequence polymorphism (number of polymorphisms, frequency spectrum, and haplotype structure) next to a selected locus depend on the frequency that the selected mutation approaches at equilibrium. We conclude that multilocus response to selection may in some cases prevent selective sweeps from being completed, as described in previous studies, but that conditions causing this to happen strongly depend on the genetic architecture of the trait, and that fixation of selected mutations is likely in many instances.

SUBMITTER: Pavlidis P

PROVIDER: S-EPMC3430538 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Selective sweeps in multilocus models of quantitative traits.

Pavlidis Pavlos P Metzler Dirk D Stephan Wolfgang W

Genetics 20120619 1

We study the trajectory of an allele that affects a polygenic trait selected toward a phenotypic optimum. Furthermore, conditioning on this trajectory we analyze the effect of the selected mutation on linked neutral variation. We examine the well-characterized two-locus two-allele model but we also provide results for diallelic models with up to eight loci. First, when the optimum phenotype is that of the double heterozygote in a two-locus model, and there is no dominance or epistasis of effects ...[more]

PMID: 22714406

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Project description:The detection of selective sweeps from population genomic data often relies on the premise that the beneficial mutations in question have fixed very near the sampling time. As it has been previously shown that the power to detect a selective sweep is strongly dependent on the time since fixation as well as the strength of selection, it is naturally the case that strong, recent sweeps leave the strongest signatures. However, the biological reality is that beneficial mutations enter populations at a rate, one that partially determines the mean wait time between sweep events and hence their age distribution. An important question thus remains about the power to detect recurrent selective sweeps when they are modelled by a realistic mutation rate and as part of a realistic distribution of fitness effects (DFE), as opposed to a single, recent, isolated event on a purely neutral background as is more commonly modelled. Here we use forward-in-time simulations to study the performance of commonly used sweep statistics, within the context of more realistic evolutionary baseline models incorporating purifying and background selection, population size change, and mutation and recombination rate heterogeneity. Results demonstrate the important interplay of these processes, necessitating caution when interpreting selection scans; specifically, false positive rates are in excess of true positive across much of the evaluated parameter space, and selective sweeps are often undetectable unless the strength of selection is exceptionally strong.Teaser textOutlier-based genomic scans have proven a popular approach for identifying loci that have potentially experienced recent positive selection. However, it has previously been shown that an evolutionarily appropriate baseline model that incorporates non-equilibrium population histories, purifying and background selection, and variation in mutation and recombination rates is necessary to reduce often extreme false positive rates when performing genomic scans. Here we evaluate the power to detect recurrent selective sweeps using common SFS-based and haplotype-based methods under these increasingly realistic models. We find that while these appropriate evolutionary baselines are essential to reduce false positive rates, the power to accurately detect recurrent selective sweeps is generally low across much of the biologically relevant parameter space.

Project description:Long-term natural and artificial selection leads to change in certain regions of the genome, resulting in selection signatures that can reveal genes associated with selected traits, such as horns (i.e., polled/horned), high-quality wool traits, and high-altitude hypoxia adaptability. These are complex traits determined by multiple genes, regulatory pathways, and environmental factors. A list of genes with considerable effects on horn and adaptability traits has not been found, although multiple quantitative trait loci (QTL) have been identified. Selection signatures could be identified using genetic differentiation (F ST ), polymorphism levels θπ, and Tajima's D. This study aimed to identify selection signatures in fine-wool sheep and to investigate the genes annotated in these regions, as well as the biological pathways involved in horn and adaptability traits. For this purpose, the whole-genome sequence of 120 individuals from four breeds, which come from different elevations and habitats in China, was used to analyze selection signatures for horn and adaptability traits. Annotation of the consensus regions of F ST and θπ ratios revealed a list of identified genes associated with polled/horned and high-altitude hypoxia adaptability traits, such as RXPF2, EERFC4, MSH6, PP1R12A, THBS1, ATP1B2, RYR2, and PLA2G2E. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified genes related primarily to mismatch repair, metabolism, vascular smooth muscle contraction, and cardiac muscle contraction. This is the first study to demonstrate that selection signatures play an important role in the polled/horned and high-altitude hypoxia adaptability traits of fine-wool sheep breeds that have undergone high-intensity selection and adapted to different ecological environments in China. Changes observed in the genome of fine-wool sheep may have acted on genomic regions that affect performance traits and provide a reference for genome design and breeding.

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Selective sweeps in multilocus models of quantitative traits.

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Selective sweeps in multilocus models of quantitative traits.

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