Show simple item record

dc.contributor.authorClemente, Florian
dc.contributor.authorCardona, Alexia
dc.contributor.authorInchley, Charlotte
dc.contributor.authorPeter, Benjamin M.
dc.contributor.authorJacobs, Guy S.
dc.contributor.authorPagani, Luca
dc.contributor.authorLawson, Daniel John
dc.contributor.authorAntao, Tiago
dc.contributor.authorVicente, Mário
dc.contributor.authorMitt, Mario
dc.contributor.authorDeGiorgio, Michael
dc.contributor.authorFaltyskova, Zuzana
dc.contributor.authorXue, Yali
dc.contributor.authorAyub, Qasim
dc.contributor.authorSzpak, Michal
dc.contributor.authorMagi, Reedik
dc.contributor.authorEriksson, Anders
dc.contributor.authorManica, Andrea
dc.contributor.authorRaghavan, Maanasa
dc.contributor.authorRasmussen, Morten
dc.contributor.authorRasmussen, Simon
dc.contributor.authorWillerslev, Eske
dc.contributor.authorVidal-Puig, Antonio
dc.contributor.authorTyler-Smith, Chris
dc.contributor.authorVillems, Richard
dc.contributor.authorNielsen, Rasmus
dc.contributor.authorMetspalu, Mait
dc.contributor.authorMalyarchuk, Boris A.
dc.contributor.authorDerenko, Miroslava V.
dc.contributor.authorKivisild, Toomas
dc.description.abstractArctic 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.
dc.relation.ispartofjournalAmerican Journal of Human Genetics
dc.subject.fieldofresearchPopulation, Ecological and Evolutionary Genetics
dc.subject.fieldofresearchBiological Sciences
dc.subject.fieldofresearchMedical and Health Sciences
dc.titleA selective sweep on a deleterious mutation in CPT1A in Arctic populations
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorWillerslev, Eske

Files in this item


There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record