The frequency spectrum of chromatin accessibility in Yorubans points toward a significant role of random genetic drift in shaping the chromatin landscape

Abstract

The function of non-coding variation in the human genome is hotly debated. While much of the genome appears to be involved in some kind of molecular activity, a relatively small portion of the genome appears to be conserved across mammalian species. To try to understand part of this seeming paradox, we examined chromatin accessibility as a model molecular phenotype. We modeled chromatin state as either open or closed as looked at the frequency of open chromatin across 70 Yoruban cell lines. We saw that most regions of chromatin accessibility occurred in only a small number of individuals, although there are a number of regions that are accessible across the entire panel. To delve further into understanding the evolutionary mechanisms, we examined nucleotide diversity in and around accessible regions. We found that in the open chromatin access, low frequency regions had decreased nucleotide diversity, however, they were situated within regions of elevated nucleotide diversity. These results point toward a role of random mutation and genetic drift shaping the distribution of accessible regions in the human genome.