A Homogenizing Process of Selection Has Maintained an “Ultra-Slow” Acetylation NAT2 Variant in Humans

Summary: By analyzing ancient and modern human genomes, the authors have discovered that the admixture during the Holocene era has obscured historic hard sweeps in modern European genomes, leading to a potential inaccuracy in our understanding of selection in human evolution.

Summary: This study integrates single-cell gene expression data with GWAS and exome sequenced data, and finds that both common and ultra-rare genetic variants associated with schizophrenia are overrepresented in specific gene-sets. These gene-sets include protein-truncating variant (PTV)-intolerant (PI) genes, genes expressed in specific brain cell types and neurons, genes defined by synaptic function and location, and genes expressed in both human and mouse brain cell gene-sets. The findings suggest that genes under stringent selection and those expressed in particular brain cell types play important roles in the biological pathways influencing the risk for schizophrenia.