Purifying Selection Influences the Comparison of Heterozygosities between Populations.

Area of Science:

• Population Genetics
• Evolutionary Biology
• Genomics

Background:

• Heterozygosity is a key metric for assessing genetic variation and effective population sizes.
• Comparisons of heterozygosity between populations are confounded by varying selection pressures across genomic regions.

Purpose of the Study:

• To investigate how selection pressure influences heterozygosity comparisons between populations of different sizes.
• To quantify the excess of nonsynonymous heterozygosity in smaller populations and identify factors modulating this excess.

Main Methods:

• Analyzed over 2 million Single Nucleotide Variants (SNVs) in chimpanzee and mouse populations.
• Compared heterozygosity estimates from neutral and nonsynonymous sites.
• Examined the influence of effective population size (N) and selection intensity (s) on nonsynonymous diversity.

Main Results:

• Small populations exhibited a 23-31% excess in nonsynonymous heterozygosity compared to neutral sites.
• This excess was greater with larger differences in effective population size between compared groups.
• Highly constrained or highly expressed genes showed a more pronounced excess of nonsynonymous heterozygosity in small populations.

Conclusions:

• Selection pressure, particularly on nonsynonymous sites, inflates heterozygosity estimates in smaller populations.
• Effective population size and gene constraint level modulate the excess of nonsynonymous heterozygosity.
• For accurate population comparisons, neutral genomic regions, less constrained genes, or lowly expressed genes are recommended.