The deleterious mutation load is insensitive to recent population history

Area of Science:

• Population genetics
• Human evolution
• Genomics

Background:

• Human populations have experienced significant demographic shifts, including rapid recent growth.
• The impact of these demographic changes on the burden of deleterious mutations and disease allele frequencies is not well understood.

Purpose of the Study:

• To investigate how recent human demographic events have influenced the burden of deleterious mutations.
• To assess the contribution of rare alleles to heritable variation in disease.

Main Methods:

• Utilized population genetic models to simulate demographic impacts.
• Analyzed two exome sequence datasets from diverse ancestral populations.

Main Results:

• Recent human demography shows little impact on the average burden of deleterious mutations.
• Individuals of West African and European ancestry exhibit similar burdens of damaging mutations.
• Rare alleles contribute minimally to heritable variation for many diseases, with modest impact from recent growth.

Conclusions:

• The average burden of deleterious mutations is largely unaffected by recent human population growth.
• Strongly deleterious rare mutations impacting fitness play a significant role in certain diseases, with their impact amplified by recent population expansion.