Differences in the rare variant spectrum among human populations

Area of Science:

• Genetics
• Population Genetics
• Genomics

Background:

• Mutation rates vary significantly across the genome and among populations.
• These variations influence the spectrum of segregating polymorphisms observed in human genomes.
• Understanding these differences is crucial for accurate population genetic inferences.

Purpose of the Study:

• To investigate variations in the rare variant spectrum across diverse human populations.
• To identify and characterize distinct mutational signatures present in different geographic groups.
• To assess the impact of these signatures on demographic inference using mutational clocks.

Main Methods:

• Analysis of rare variant spectra in a global sample of human genomes.
• Identification of specific mutation patterns (e.g., TCC>TTC, CpG site mutations).
• Comparison of mutation signatures in ancient and archaic human genomes.
• Modeling the influence of demography on mutation spectra.

Main Results:

• Two distinct mutational signatures were identified across human populations.
• A TCC>TTC mutation signature, linked to methylated guanine deamination, was observed in Western Eurasian and South Asian populations.
• A second signature, specific to Native American populations, was concentrated at CpG sites and influenced by recent demography.

Conclusions:

• Geographic and demographic factors significantly shape the rare variant spectrum in human genomes.
• Distinct mutational signatures have implications for interpreting genetic variation and evolutionary history.
• Accurate demographic inference requires accounting for population-specific mutation patterns and their underlying mechanisms.