Widespread Genomic Signatures of Natural Selection in Hominid Evolution

By Graham P. McVicker, David Gordon, C. Davis, Phil Green. 2009

450 citations recorded by the source corpus.

Selection acting on genomic functional elements can be detected by its indirect effects on population diversity at linked neutral sites. To illuminate the selective forces that shaped hominid evolution, we analyzed the genomic distributions of human polymorphisms and sequence differences among five primate species relative to the locations of conserved sequence features. Neutral sequence diversity in human and ancestral hominid populations is substantially reduced near such features, resulting in a surprisingly large genome average diversity reduction due to selection of 19–26% on the autosomes and 12–40% on the X chromosome. The overall trends are broadly consistent with “background selection” or hitchhiking in ancestral populations acting to remove deleterious variants. Average selection is much stronger on exonic (both protein-coding and untranslated) conserved features than non-exonic features. Long term selection, rather than complex speciation scenarios, explains the large intragenomic variation in human/chimpanzee divergence. Our analyses reveal a dominant role for selection in shaping genomic diversity and divergence patterns, clarify hominid evolution, and provide a baseline for investigating specific selective events.

Subfields: Genetics, Molecular Biology

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Citations in the corpus

A general framework for estimating the relative pathogenicity of human genetic variants (2014, background): “…scores, element scores and p-values 54 , also defined from alignments with the human reference excluded; background selection score 40,55 ; expression value, H3K27 acetylation, H3K4 methylation, H3K4 trimethylation, nucleosome occupancy and open chromatin tracks provided for ENCODE…”
Genome-Wide Inference of Ancestral Recombination Graphs (2013, background): “We attribute this reduction primarily to the effects of selection from linked sites (see [60]), although direct selection from mRNA secondary structure and exonic regulatory elements may also contribute to it.”
Insights into hominid evolution from the gorilla genome sequence (2012, background): “Given that morethan90%ofthe genomelies within300kbpofa codinggene, and noting the similar phenomenon reported for recent human evolution 12 ,this supportsthe suggestionthatselectionhasaffected almost all of the genome throughout hominid evolution 18 .”
Approximation to the Distribution of Fitness Effects across Functional Categories in Human Segregating Polymorphisms (2014, unknown): “We tested the robustness of the mappings to diﬀerent levels of background selection, by partitioning the data into deciles of B-scores [35] and re-computing the C-to-s mapping for each decile.”
dbNSFP v4: a comprehensive database of transcript-specific functional predictions and annotations for human nonsynonymous and splice-site SNVs (2020, background): “…MVP [27], PrimateAI [28], REVEL [29], SIFT4G [30]), one score for loss of function prediction (ALoFT [31]), and three conservation scores (phyloP17-way_primate [32], phastCons17way_primate [33], bStatistic [34]), making the total number of prediction scores to 46 (Additional file 1: Table S1).”
The Genetics of Human Adaptation: Hard Sweeps, Soft Sweeps, and Polygenic Adaptation (2010, unknown): “Taken together, these observations are most easily explained by either widespread positive selection, or possibly by background selection against mildly deleterious alleles [29,32].”
Estimating and interpreting FST: The impact of rare variants (2013, background): “Indeed, variation in FST estimates between ascertained classes of SNPs can be used to test a variety of hypotheses about population history (Weir et al. 2005; McVicker et al. 2009).”
Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program (2019, methodology): “We measured how the site frequency spectrum and demographic inference changed as a function of sample size and an index of selection at linked sites (McVicker’s B statistic 60 ) using TOPMed individuals whose genomes suggested mostly European ancestry and low admixture.”