The evolutionary and functional impact of the hominin-specific acyl-CoA thioesterase (ACOT1) gene duplication on metabolic health

Authors: Carsyn Bonesteel, Omer Gokcumen

SUNY Campus: SUNY Buffalo

Presentation Type: Poster

Location: UU 111

Presentation #: 76

Timeslot: Session C 1:45-2:45 PM

Abstract: This study investigates the genomic, evolutionary, and functional impact of the human-specific ACOT1 gene duplication, which originated from ACOT2 and remains polymorphic across populations. ACOT1 copy number variation (CNV) is linked to liver function, fat mass, diabetes, breast milk fat, and lipid metabolism, but its evolutionary history and mechanisms remain unclear. Using long-read sequencing from 107 individuals and short-read sequencing from thousands more, we reconstructed the 6 structural haplotypes at the ACOT locus and their evolutionary history using phylogenetic trees and haplotype networks. Our findings show that the ACOT1 duplication predates the out-of Africa-migration, occurring over 50,000 years ago. We also identified complex ACOT haplotypes, signifying recurrent subsequent duplications of ACOT1, ACOT2, and ACOT1 and 2, We aligned ACOT1 and ACOT2 sequences across individuals and species to characterize sequence divergence, identify duplication breakpoints, and assess population variation. We found 316 divergent single nucleotide variants (SNVs) between ACOT1 and ACOT2 genes. Future work will integrate these SNVs with genome-wide association study data to explore links between ACOT1 CNV and metabolic traits. Further population genetic approaches will assess whether selection influenced ACOT1 CNV frequencies, shedding light on its adaptive role in metabolic regulation. The findings could ultimately contribute to personalized approaches for studying metabolic disorders and unraveling gene-environment interactions in human evolution.