Most Recent Common Ancestor Probability Distributions in Gene Genealogies under Selection

Slade, Paul F.

doi:10.1006/tpbi.2000.1488

Cited by 30 publications

(29 citation statements)

References 7 publications

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“…Donnelly and Kurtz (1999) made the sensible conjecture that the expected fitness of a common ancestral allele will exceed that of a randomly selected allele from the population. Slade (2000) and Fearnhead (2002) corroborated the conjecture with simulation and analytical treatments, respectively, using the ancestral selection graph technique of Krone and Neuhauser (1997). Because nonsynonymous SNPs (nsSNPs) are expected to be more deleterious than synonymous SNPs (sSNPs), these results coincide with empirical findings such as the tendency of nsSNPs to have lower allele frequencies than sSNPs (Cargill et al, 1999).…”

Section: Introductionsupporting

confidence: 70%

“…Watterson and Guess (1977) noted that if mutation rates are not negligible, the most frequent allele is less likely to be oldest. Likewise, if genetic variation is not neutral, the probability that an allele is ancestral is no longer the allele frequency (e.g., Slade, 2000; Fearnhead, 2002; Taylor, 2007). New mutations are more commonly deleterious than advantageous and new deleterious mutations are unlikely to reach high or even moderate allele frequencies before being lost.…”

Section: Introductionmentioning

confidence: 99%

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Estimates of natural selection due to protein tertiary structure inform the ancestry of biallelic loci

Choi

Stone

Kishino

et al. 2009

Gene

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We consider the inference of which of two alleles is ancestral when the alleles have a single nonsynonymous difference and when natural selection acts via protein tertiary structure. Whereas the probability that an allele is ancestral under neutrality is equal to its frequency, under selection this probability depends on allele frequency and on the magnitude and direction of selection pressure. Although allele frequencies can be well estimated from intraspecific data, small fitness differences have a large evolutionary impact but can be difficult to estimate with only intraspecific data. Methods for predicting aspects of phenotype from genotype can supplement intraspecific sequence data. Recently developed statistical techniques can assess effects of phenotypes, such as protein tertiary structure on molecular evolution. While these techniques were initially designed for comparing protein-coding genes from different species, the resulting interspecific inferences can be assigned population genetic interpretations to assess the effect of selection pressure, and we use them here along with intraspecific allele frequency data to estimate the probability that an allele is ancestral. We focus on 140 nonsynonymous single nucleotide polymorphisms of humans that are in proteins with known tertiary structures. We find that our technique for employing protein tertiary structure information yields some biologically plausible results but that it does not substantially improve the inference of ancestral human allele types.

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Section: Introductionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Estimates of natural selection due to protein tertiary structure inform the ancestry of biallelic loci

Choi

Stone

Kishino

et al. 2009

Gene

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“…These may be estimated more easily, simply using recursions regardless of inter-arrival times between events in the graph and so without need for decomposition into real and virtual ancestors. A further simplification of the selective branching structure as developed in Slade (2000b) for a single locus model would also apply.…”

Section: Discussionmentioning

confidence: 99%

Simulation of ‘hitch-hiking’ genealogies

Slade

2001

J Math Biol

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An ancestral influence graph is derived, an analogue of the coalescent and a composite of Griffiths' (1991) two-locus ancestral graph and Krone and Neuhauser's (1997) ancestral selection graph. This generalizes their use of branching-coalescing random graphs so as to incorporate both selection and recombination into gene genealogies. Qualitative understanding of a 'hitch-hiking' effect on genealogies is pursued via diagrammatic representation of the genealogical process in a two-locus, two-allele haploid model. Extending the simulation technique of Griffiths and Tavare (1996), computational estimation of expected times to the most recent common ancestor of samples of n genes under recombination and selection in two-locus, two-allele haploid and diploid models are presented. Such times are conditional on sample configuration. Monte Carlo simulations show that 'hitch-hiking' is a subtle effect that alters the conditional expected depth of the genealogy at the linked neutral locus depending on a mutation-selection-recombination balance.

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“…For moderate or strong selection, the ASG becomes so large that the computation becomes intractable. The ASG method’s performance was dramatically improved by truncating the ASG (Slade 2000) to avoid generating very large ASGs. This approach, however, has not been extended to the analysis of multiple linked neutral mutations.…”

Section: Introductionmentioning

confidence: 99%

Inferring Selection Intensity and Allele Age from Multilocus Haplotype Structure

Chen

Slatkin

2013

G3 Genes|Genomes|Genetics

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It is a challenging task to infer selection intensity and allele age from population genetic data. Here we present a method that can efficiently estimate selection intensity and allele age from the multilocus haplotype structure in the vicinity of a segregating mutant under positive selection. We use a structured-coalescent approach to model the effect of directional selection on the gene genealogies of neutral markers linked to the selected mutant. The frequency trajectory of the selected allele follows the Wright-Fisher model. Given the position of the selected mutant, we propose a simplified multilocus haplotype model that can efficiently model the dynamics of the ancestral haplotypes under the joint influence of selection and recombination. This model approximates the ancestral genealogies of the sample, which reduces the number of states from an exponential function of the number of single-nucleotide polymorphism loci to a quadratic function. That allows parameter inference from data covering DNA regions as large as several hundred kilo-bases. Importance sampling algorithms are adopted to evaluate the probability of a sample by exploring the space of both allele frequency trajectories of the selected mutation and gene genealogies of the linked sites. We demonstrate by simulation that the method can accurately estimate selection intensity for moderate and strong positive selection. We apply the method to a data set of the G6PD gene in an African population and obtain an estimate of 0.0456 (95% confidence interval 0.0144−0.0769) for the selection intensity. The proposed method is novel in jointly modeling the multilocus haplotype pattern caused by recombination and mutation, allowing the analysis of haplotype data in recombining regions. Moreover, the method is applicable to data from populations under exponential growth and a variety of other demographic histories.

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Most Recent Common Ancestor Probability Distributions in Gene Genealogies under Selection

Cited by 30 publications

References 7 publications

Estimates of natural selection due to protein tertiary structure inform the ancestry of biallelic loci

Estimates of natural selection due to protein tertiary structure inform the ancestry of biallelic loci

Simulation of ‘hitch-hiking’ genealogies

Inferring Selection Intensity and Allele Age from Multilocus Haplotype Structure

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