A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations
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 da...
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ftcdlib:oai:escholarship.org:ark:/13030/qt8064x8wh 2023-10-25T01:34:59+02:00 A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations Clemente, Florian J Cardona, Alexia Inchley, Charlotte E Peter, Benjamin M Jacobs, Guy Pagani, Luca Lawson, Daniel J Antão, Tiago Vicente, Mário Mitt, Mario DeGiorgio, Michael Faltyskova, Zuzana Xue, Yali Ayub, Qasim Szpak, Michal Mägi, Reedik Eriksson, Anders Manica, Andrea Raghavan, Maanasa Rasmussen, Morten Rasmussen, Simon Willerslev, Eske Vidal-Puig, Antonio Tyler-Smith, Chris Villems, Richard Nielsen, Rasmus Metspalu, Mait Malyarchuk, Boris Derenko, Miroslava Kivisild, Toomas 584 - 589 2014-11-01 application/pdf https://escholarship.org/uc/item/8064x8wh unknown eScholarship, University of California qt8064x8wh https://escholarship.org/uc/item/8064x8wh public American Journal of Human Genetics, vol 95, iss 5 Biological Sciences Genetics Human Genome Medical and Health Sciences Genetics & Heredity Biomedical and clinical sciences Health sciences article 2014 ftcdlib 2023-09-25T18:03:13Z 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 79protein-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 sweephas 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. Article in Journal/Newspaper Arctic Greenland inuits University of California: eScholarship Arctic Greenland |
institution |
Open Polar |
collection |
University of California: eScholarship |
op_collection_id |
ftcdlib |
language |
unknown |
topic |
Biological Sciences Genetics Human Genome Medical and Health Sciences Genetics & Heredity Biomedical and clinical sciences Health sciences |
spellingShingle |
Biological Sciences Genetics Human Genome Medical and Health Sciences Genetics & Heredity Biomedical and clinical sciences Health sciences Clemente, Florian J Cardona, Alexia Inchley, Charlotte E Peter, Benjamin M Jacobs, Guy Pagani, Luca Lawson, Daniel J Antão, Tiago Vicente, Mário Mitt, Mario DeGiorgio, Michael Faltyskova, Zuzana Xue, Yali Ayub, Qasim Szpak, Michal Mägi, Reedik Eriksson, Anders Manica, Andrea Raghavan, Maanasa Rasmussen, Morten Rasmussen, Simon Willerslev, Eske Vidal-Puig, Antonio Tyler-Smith, Chris Villems, Richard Nielsen, Rasmus Metspalu, Mait Malyarchuk, Boris Derenko, Miroslava Kivisild, Toomas A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations |
topic_facet |
Biological Sciences Genetics Human Genome Medical and Health Sciences Genetics & Heredity Biomedical and clinical sciences Health sciences |
description |
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 79protein-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 sweephas 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. |
format |
Article in Journal/Newspaper |
author |
Clemente, Florian J Cardona, Alexia Inchley, Charlotte E Peter, Benjamin M Jacobs, Guy Pagani, Luca Lawson, Daniel J Antão, Tiago Vicente, Mário Mitt, Mario DeGiorgio, Michael Faltyskova, Zuzana Xue, Yali Ayub, Qasim Szpak, Michal Mägi, Reedik Eriksson, Anders Manica, Andrea Raghavan, Maanasa Rasmussen, Morten Rasmussen, Simon Willerslev, Eske Vidal-Puig, Antonio Tyler-Smith, Chris Villems, Richard Nielsen, Rasmus Metspalu, Mait Malyarchuk, Boris Derenko, Miroslava Kivisild, Toomas |
author_facet |
Clemente, Florian J Cardona, Alexia Inchley, Charlotte E Peter, Benjamin M Jacobs, Guy Pagani, Luca Lawson, Daniel J Antão, Tiago Vicente, Mário Mitt, Mario DeGiorgio, Michael Faltyskova, Zuzana Xue, Yali Ayub, Qasim Szpak, Michal Mägi, Reedik Eriksson, Anders Manica, Andrea Raghavan, Maanasa Rasmussen, Morten Rasmussen, Simon Willerslev, Eske Vidal-Puig, Antonio Tyler-Smith, Chris Villems, Richard Nielsen, Rasmus Metspalu, Mait Malyarchuk, Boris Derenko, Miroslava Kivisild, Toomas |
author_sort |
Clemente, Florian J |
title |
A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations |
title_short |
A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations |
title_full |
A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations |
title_fullStr |
A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations |
title_full_unstemmed |
A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations |
title_sort |
selective sweep on a deleterious mutation in cpt1a in arctic populations |
publisher |
eScholarship, University of California |
publishDate |
2014 |
url |
https://escholarship.org/uc/item/8064x8wh |
op_coverage |
584 - 589 |
geographic |
Arctic Greenland |
geographic_facet |
Arctic Greenland |
genre |
Arctic Greenland inuits |
genre_facet |
Arctic Greenland inuits |
op_source |
American Journal of Human Genetics, vol 95, iss 5 |
op_relation |
qt8064x8wh https://escholarship.org/uc/item/8064x8wh |
op_rights |
public |
_version_ |
1780730187588042752 |