Interrogating a high-density SNP map for signatures of natural selection.

By Joshua M. Akey, Ge Zhang, Kun Zhang, Li Jin, Mark D. Shriver. Genome Research, 2002

930 citations recorded by the source corpus.

Identifying genomic regions that have been targets of natural selection remains one of the most important and challenging areas of research in genetics. To this end, we report an analysis of 26,530 single nucleotide polymorphisms (SNPs) with allele frequencies that were determined in three populations. Specifically, we calculated a measure of genetic differentiation, F(ST), for each locus and examined its distribution at the level of the genome, the chromosome, and individual genes. Through a variety of analyses, we have found statistically significant evidence supporting the hypothesis that selection has influenced extant patterns of human genetic variation. Importantly, by contrasting the F(ST) of individual SNPs to the empirical genome-wide distribution of F(ST), our results are not confounded by tenuous assumptions of population demographic history. Furthermore, we have identified 174 candidate genes with distribution of genetic variation that indicates that they have been targets of selection. Our work provides a first generation natural selection map of the human genome and provides compelling evidence that selection has shaped extant patterns of human genomic variation.

Subfields: Genetics

View Paper: https://www.semanticscholar.org/paper/9f0f5ea38977e81e44cb0ac76c6cc1f3afa7b7aa

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Citations in the corpus

Ancestry informative markers for fine-scale individual assignment to worldwide populations (2010, neutral): “In fact, population differentiation has been considered as an indication of selective pressure, and several genome scans for natural selection were based on the identification of loci that appear as outliers in empirical distributions of genotypic patterns (see [49, 50, 51, 6, 52, 53] among others).”
Balancing Selection and Its Effects on Sequences in Nearby Genome Regions (2006, neutral): “FST-based tests for selection are already in use [76,77].”
Impact of selection, mutation rate and genetic drift on human genetic variation. (2003, background): “While previous analyses detected high levels of deleterious SNPs in the human population (4, 16, 29-34) here we show that selection is strong enough to prevent their fixation.”
Identifying adaptive genetic divergence among populations from genome scans (2004, methodology): “Akey et al. 2002 using SNPs; Kayser et al. 2003 using microsatellites) and in other populations of evolutionary interest (Wilding et al. 2001; Storz and Nachman 2003). A variety of different statistical methods have been developed from the original idea of Lewontin and Krakauer (Bowcock et al. 1991;”
Genetics in geographically structured populations: defining, estimating and interpreting FST (2009, background): “Genome scans that compare single-locus estimates of F ST with the genome-wide background might therefore identify regions of the genome that have been subjected to diversifying selection”
Informativeness of genetic markers for inference of ancestry. (2003, methodology): “From the Akey et al. (2002) data, we exclude several types of SNPs: (1) SNPs genotyped by the Whitehead Institute, whose European American sample differed from that used by the other genotyping centers; (2) SNPs with unknown sample sizes or with sample size !”
The evolution of molecular markers — just a matter of fashion? (2004, background): “Similarly, candidate regions were also identified by a recent SNP genome sca”
Identifying targets and agents of selection: innovative methods to evaluate the processes that contribute to local adaptation (2017, background): “of selection in one environment and its absence in another suggests that underlying genes may control locally-adaptive traits (Akey et al. 2002; Namroud et al. 2008; Shimada, Shikano & Meril€a 2011).”
Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones (2004, neutral): “Due to the rapidly increasing accumulation of genetic polymorphism data, it is necessary to classify the polymorphism data with respect to gene structure in order to elucidate potential biological effects (Gaudieri et al. 2000; Sachidanandam et al. 2001; Akey et al. 2002; Bamshad and Wooding 2003).”
Genetic signatures of strong recent positive selection at the lactase gene. (2004, methodology): “Large differences in allele frequencies between populations have traditionally been detected by use of the population-genetics measure F ST (e.g., Akey et al. 2002), whereas demonstration that a common haplotype is unexpectedly long requires application of the recently described long-range…”
Quantifying unobserved protein-coding variants in human populations provides a roadmap for large-scale sequencing projects (2016, neutral): “The frequency distribution of rare variants thus reﬂects a conﬂuence of several important processes including the demographic history of the population 8–10 and the forces of selection acting on these variants 11,12 .”
The Pattern of Polymorphism in Arabidopsis thaliana (2005, background): “This pattern is of interest in that regions with extremely high or low values may be seen as candidates for harboring selectively important loci [23,24].”