Analysis of 6,515 exomes reveals a recent origin of most human protein-coding variants

Establishing the age of each mutation segregating in contemporary human populations is important to fully understand our evolutionary history 1,2 and will help facilitate the development of new approaches for disease gene discovery 3 . Large-scale surveys of human genetic variation have reported signatures of recent explosive population growth 4-6 , notable for an excess of rare genetic variants, qualitatively suggesting that many mutations arose recently. To more quantitatively assess the distribution of mutation ages, we resequenced 15,336 genes in 6,515 individuals of European (n=4,298) and African (n=2,217) American ancestry and inferred the age of 1,146,401 autosomal single nucleotide variants (SNVs). We estimate that ~73% of all protein-coding SNVs and ~86% of SNVs predicted to be deleterious arose in the past 5,000-10,000 years. The average age of deleterious SNVs varied significantly across molecular pathways, and disease

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