  Human populations have undergone dramatic changes in population size in the
past 100,000 years, including a severe bottleneck of non-African populations
and recent explosive population growth. There is currently great interest in
how these demographic events may have affected the burden of deleterious
mutations in individuals and the allele frequency spectrum of disease mutations
in populations. Here we use population genetic models to show that--contrary to
previous conjectures--recent human demography has likely had very little impact
on the average burden of deleterious mutations carried by individuals. This
prediction is supported by exome sequence data showing that African American
and European American individuals carry very similar burdens of damaging
mutations. We next consider whether recent population growth has increased the
importance of very rare mutations in complex traits. Our analysis predicts that
for most classes of disease variants, rare alleles are unlikely to contribute a
large fraction of the total genetic variance, and that the impact of recent
growth is likely to be modest. However, for diseases that have a direct impact
on fitness, strongly deleterious rare mutations likely do play important roles,
and the impact of very rare mutations will be far greater as a result of recent
growth. In summary, demographic history has dramatically impacted patterns of
variation in different human populations, but these changes have likely had
little impact on either genetic load or on the importance of rare variants for
most complex traits.

Populations and Evolution