A selective sweep on a deleterious mutation in CPT1A in Arctic populations

Florian J. Clemente, Alexia Cardona, Charlotte E. Inchley, Benjamin M. Peter, Guy Jacobs, Luca Pagani, Daniel John Lawson, Tiago Antão, Mário Vicente, Mario Mitt, Michael DeGiorgio, Zuzana Faltyskova, Yali Xue, Qasim Ayub, Michal Szpak, Reedik Mägi, Anders Eriksson, Andrea Manica, Maanasa Raghavan, Morten Arendt Rendt RasmussenSimon B. Rasmussen, Eske Willerslev, Antonio J. Vidal-Puig, Chris Tyler-Smith, Richard Villems, Rasmus Wedel Nielsen, Mait Metspalu, Boris A. Malyarchuk, Miroslava V. Derenko, Toomas Kivisild

Research output: Contribution to journalArticlepeer-review

108 Scopus citations


Arctic populations live in an environment characterized by extreme cold and the absence of plant foods for much of the year and are likely to have undergone genetic adaptations to these environmental conditions in the time they have been living there. Genome-wide selection scans based on genotype data from native Siberians have previously highlighted a 3 Mb chromosome 11 region containing 79 protein-coding genes as the strongest candidates for positive selection in Northeast Siberians. However, it was not possible to determine which of the genes might be driving the selection signal. Here, using whole-genome high-coverage sequence data, we identified the most likely causative variant as a nonsynonymous G>A transition (rs80356779; c.1436C>T [p.Pro479Leu] on the reverse strand) in CPT1A, a key regulator of mitochondrial long-chain fatty-acid oxidation. Remarkably, the derived allele is associated with hypoketotic hypoglycemia and high infant mortality yet occurs at high frequency in Canadian and Greenland Inuits and was also found at 68% frequency in our Northeast Siberian sample. We provide evidence of one of the strongest selective sweeps reported in humans; this sweep has driven this variant to high frequency in circum-Arctic populations within the last 6-23 ka despite associated deleterious consequences, possibly as a result of the selective advantage it originally provided to either a high-fat diet or a cold environment.
Original languageEnglish (US)
Pages (from-to)584-589
Number of pages6
JournalThe American Journal of Human Genetics
Issue number5
StatePublished - Nov 2014

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'A selective sweep on a deleterious mutation in CPT1A in Arctic populations'. Together they form a unique fingerprint.

Cite this