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...
Published in: | The American Journal of Human Genetics |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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2014
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Online Access: | https://hdl.handle.net/1983/3aec6210-906a-4ed5-892b-99c205bd616c https://research-information.bris.ac.uk/en/publications/3aec6210-906a-4ed5-892b-99c205bd616c https://doi.org/10.1016/j.ajhg.2014.09.016 |
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ftubristolcris:oai:research-information.bris.ac.uk:publications/3aec6210-906a-4ed5-892b-99c205bd616c 2024-04-28T08:05:01+00:00 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 2014-10-23 https://hdl.handle.net/1983/3aec6210-906a-4ed5-892b-99c205bd616c https://research-information.bris.ac.uk/en/publications/3aec6210-906a-4ed5-892b-99c205bd616c https://doi.org/10.1016/j.ajhg.2014.09.016 eng eng https://research-information.bris.ac.uk/en/publications/3aec6210-906a-4ed5-892b-99c205bd616c info:eu-repo/semantics/restrictedAccess Clemente , F J , Cardona , A , Inchley , C E , Peter , B M , Jacobs , G , Pagani , L , Lawson , D J , Antão , T , Vicente , M , Mitt , M , DeGiorgio , M , Faltyskova , Z , Xue , Y , Ayub , Q , Szpak , M , Mägi , R , Eriksson , A , Manica , A , Raghavan , M , Rasmussen , M , Rasmussen , S , Willerslev , E , Vidal-Puig , A , Tyler-Smith , C , Villems , R , Nielsen , R , Metspalu , M , Malyarchuk , B , Derenko , M & Kivisild , T 2014 , ' A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations ' , American Journal of Human Genetics , vol. 95 , no. 5 , pp. 584-589 . https://doi.org/10.1016/j.ajhg.2014.09.016 article 2014 ftubristolcris https://doi.org/10.1016/j.ajhg.2014.09.016 2024-04-03T15:23:47Z 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. Article in Journal/Newspaper Arctic Arctic Greenland inuits University of Bristol: Bristol Research The American Journal of Human Genetics 95 5 584 589 |
institution |
Open Polar |
collection |
University of Bristol: Bristol Research |
op_collection_id |
ftubristolcris |
language |
English |
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 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. |
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 |
spellingShingle |
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 |
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 |
publishDate |
2014 |
url |
https://hdl.handle.net/1983/3aec6210-906a-4ed5-892b-99c205bd616c https://research-information.bris.ac.uk/en/publications/3aec6210-906a-4ed5-892b-99c205bd616c https://doi.org/10.1016/j.ajhg.2014.09.016 |
genre |
Arctic Arctic Greenland inuits |
genre_facet |
Arctic Arctic Greenland inuits |
op_source |
Clemente , F J , Cardona , A , Inchley , C E , Peter , B M , Jacobs , G , Pagani , L , Lawson , D J , Antão , T , Vicente , M , Mitt , M , DeGiorgio , M , Faltyskova , Z , Xue , Y , Ayub , Q , Szpak , M , Mägi , R , Eriksson , A , Manica , A , Raghavan , M , Rasmussen , M , Rasmussen , S , Willerslev , E , Vidal-Puig , A , Tyler-Smith , C , Villems , R , Nielsen , R , Metspalu , M , Malyarchuk , B , Derenko , M & Kivisild , T 2014 , ' A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations ' , American Journal of Human Genetics , vol. 95 , no. 5 , pp. 584-589 . https://doi.org/10.1016/j.ajhg.2014.09.016 |
op_relation |
https://research-information.bris.ac.uk/en/publications/3aec6210-906a-4ed5-892b-99c205bd616c |
op_rights |
info:eu-repo/semantics/restrictedAccess |
op_doi |
https://doi.org/10.1016/j.ajhg.2014.09.016 |
container_title |
The American Journal of Human Genetics |
container_volume |
95 |
container_issue |
5 |
container_start_page |
584 |
op_container_end_page |
589 |
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1797575324400091136 |