The deleterious mutation load is insensitive to recent population history

• Published in: Nature genetics Vol. 46; no. 3; pp. 220 - 224
• Main Authors: Simons, Yuval B, Turchin, Michael C, Pritchard, Jonathan K, Sella, Guy
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2014; Nature Publishing Group
• Subjects: 45; 45/23; 631/114; 631/208/212; 631/208/457; Agriculture; analysis; Animal Genetics and Genomics; Biomedicine; Blacks - genetics; Cancer Research; Demographics; Demography; Disease; Evolution; Exome; Gene Function; Gene mutations; Genetic Load; Genetic research; Genetics, Population; Growth; Human Genetics; Human populations; Humans; Identification and classification; Models, Genetic; Mutation; Nucleotide sequence; Parameter estimation; Polymorphism, Single Nucleotide; Population; Population Dynamics; Population growth; Population number; Testing; Whites - genetics
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng.2896

Jonathan Pritchard, Guy Sella and colleagues report an analysis using population genetic models to show that recent human demography is likely to have had little impact on the average burden of deleterious mutations. They examine two large exome sequence datasets and find that individuals of west African and European ancestry carry similar burdens of damaging mutations. Human populations have undergone major changes in population size in the past 100,000 years, including recent rapid growth. How these demographic events have affected the burden of deleterious mutations in individuals and the frequencies of disease mutations in populations remains unclear. We use population genetic models to show that recent human demography has probably had little impact on the average burden of deleterious mutations. This prediction is supported by two exome sequence data sets showing that individuals of west African and European ancestry carry very similar burdens of damaging mutations. We further show that for many diseases, rare alleles are unlikely to contribute a large fraction of the heritable variation, and therefore the impact of recent growth is likely to be modest. However, for those diseases that have a direct impact on fitness, strongly deleterious rare mutations probably do have an important role, and recent growth will have increased their impact.