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Docquier, M.

Publications and source records attributed to Docquier, M..

2 recordsLinked to original sources

Cultural norms of exogamy and mobility shape hunter-gatherer genetic evolution

Through a hunting and gathering lifestyle, humans have managed to thrive across all terrestrial ecosystems. A key adaptive feature enabling this ecological success is the ability of hunter-gatherer societies to maintain high levels of genetic diversity despite ecological and demographic shocks, but the mechanisms underlying this resilience are poorly understood. Here we integrate genomic, demographic, mobility and ethnographic data from two Central African hunter-gatherer populations to show that genetic diversity emerges from interacting effects of population size, mobility and cultural norms governing marriage. We first demonstrate direct selection against background homozygosity: even modest increases in runs of homozygosity, in the near absence of close-kin marriage, are associated with reduced reproductive success. Despite regional differences in effective population size, clustering of relatives, sedentism and exogamy rules, overall levels of homozygosity are similarly low in both populations. These shared genetic outcomes are achieved through distinct strategies: in one region, strict exogamy combined with high lifetime mobility limits local relatedness, whereas in the other, more relaxed exogamy norms are offset by increased male mate-search distances that reduce offspring homozygosity. Together, our results show that human populations flexibly adjust mobility and social norms to demographic constraints to preserve genetic diversity and avoid fitness costs, revealing culture as a central component of human adaptation.

genetics↗

CRISPR screen decodes SWI/SNF chromatin remodeling complex assembly

The SWI/SNF (or BAF) complex is an essential chromatin remodeler that regulates DNA accessibility at developmental genes and enhancers. SWI/SNF subunits are among the most frequently mutated genes in cancer and neurodevelopmental disorders. These mutations are often heterozygous loss-of-function alleles, indicating a dosage-sensitive role for SWI/SNF subunits in chromatin regulation. However, the molecular mechanisms that regulate SWI/SNF subunit dosage to ensure proper complex assembly remain largely unexplored. We performed a genome-wide CRISPR KO screen, using epigenome editing in mouse embryonic stem cells, and identified Mlf2 and Rbm15 as regulators of SWI/SNF complex activity. First, we show that MLF2, a poorly characterized chaperone protein, regulates a subset of SWI/SNF target genes by promoting chromatin remodeling activity. Next, we find that RBM15, part of the m6A RNA methylation writer complex, controls m6A modifications on specific SWI/SNF mRNAs to regulate protein levels of these subunits. Misregulation of m6A methylation causes overexpression of core SWI/SNF subunits leading to the assembly of incomplete complexes lacking the catalytic ATPase/ARP subunits. These data indicate that targeting modulators of SWI/SNF complex assembly may offer a potent therapeutic strategy for diseases associated with impaired chromatin remodeling.

molecular biology↗