Abstract
The influence of long-term climatic changes such as glacial cycles on the history of living organisms has been a subject of research for decades, but the detailed population dynamics during the environmental fluctuations and their effects on genetic diversity and genetic load are not well understood on a genome-wide scale. The Japanese macaque (Macaca fuscata) is a unique primate adapted to the cold environments of the Japanese archipelago. Despite the past intensive research for the Japanese macaque population genetics, the genetic background of Japanese macaques at the whole-genome level has been limited to a few individuals, and the comprehensive demographic history and genetic differentiation of Japanese macaques have been underexplored. We conducted whole-genome sequencing of 64 Japanese macaque individuals from 5 different regions, revealing significant genetic differentiation and functional variant diversity across populations. In particular, Japanese macaques have low genetic diversity and harbor many shared and population-specific gene loss, which might contribute to population-specific phenotypes. Our estimation of population demography using phased haplotypes suggested that, after the strong population bottleneck shared among all populations around 400 to 500 kya, the divergence among populations initiated around 150 to 200 kya, but there has been the time with strong gene flow between some populations after the split, indicating multiple population split and merge events probably due to habitat fragmentation and fusion during glacial cycles. These findings not only present a complex population history of Japanese macaques but also enhance their value as research models, particularly in neuroscience and behavioral studies. This comprehensive genomic analysis sheds light on the adaptation and evolution of Japanese macaques, contributing valuable insights to both evolutionary biology and biomedical research.