population expansion
Simons YB, Turchin MC, Pritchard JK & Sella G 2014 The deleterious mutation load is insensitive to recent population history. Nat Genet 46:220-224.
- with growth, the increased number of segregating sites is balanced exactly by a decrease in the mean frequency
- the mean number of deleterious variants per individual drops by 60% as a result of the bottleneck
- this drop is due to the loss of rare alleles
- during the bottleneck, some deleterious alleles drift to higher frequencies11,19, contributing disproportionately to the number of homozygotes
- this causes a transient increase in the number of deleterious homozygous sites per individual, i.e., the recessive load
- there are large absolute numbers of rare variants
- they do not necessarily contribute a large fraction of the genetic variance underlying complex traits
- an earlier paper from one of the present authors (Pritchard, 2001 (ref. 13)) also discussed the possible role of allelic heterogeneity and rare variants in disease using a model that is closer to the independent s model examined here
- the bulk of the genetic variance was predicted to be due to variants that would not be considered rare by modern standards
- it is only for diseases that are caused primarily by strongly deleterious mutations that we can expect much of the variance to be due to rare alleles
- these will likely be diseases that are tightly coupled to fitness
