Selected Grantee Publications

Identification of Constrained Sequence Elements Across 239 Primate Genomes

Kuderna et al., Nature. 2024.

https://pubmed.ncbi.nlm.nih.gov/38030727/

Functional genomic elements that have acquired selective constraints specific to the primate order are prime candidates for understanding evolutionary changes in humans, but the selective constraints specific to the phylogenetic branch from which the human species ultimately emerged remain largely unidentified. Researchers constructed a genome-wide multiple sequence alignment of 239 primate species to better characterize constraint at noncoding regulatory sequences in the human genome. Their work reveals noncoding regulatory elements that are under selective constraint in primates but not in other placental mammals and are enriched for variants that affect human gene expression and complex traits in diseases. These findings highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals. Supported by ORIP (P40OD024628), NHGRI, NIA, and NICHD.