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: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Other Authors: | , , , , , , , , , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | unknown |
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Elsevier BV
2014
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Subjects: | |
Online Access: | http://hdl.handle.net/10754/563835 https://doi.org/10.1016/j.ajhg.2014.09.016 |
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Open Polar |
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King Abdullah University of Science and Technology: KAUST Repository |
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ftkingabdullahun |
language |
unknown |
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. This research was supported by European Research Council Starting Investigator grant FP7-261213 to T.K. C.T.-S., Y.X., Q.A., and M.S. were supported by Wellcome Trust grant 098051, and T.A. was supported by Wellcome Trust grant WT100066MA. M. Metspalu and R.V. received supported from the European Union European Regional Development Fund Centre of Excellence in Genomics to the Estonian Biocentre. T.K, M. Metspalu, and R.V. were supported by Estonian Institutional Research grant IUT24-1, and M. Metspalu received Estonian Science Foundation grant 8973. |
author2 |
Biological and Environmental Sciences and Engineering (BESE) Division Bioscience Program Integrative Systems Biology Lab Department of Archaeology and Anthropology, University of CambridgeCambridge, United Kingdom Department of Integrative Biology, University of California, BerkeleyBerkeley, CA, United States Mathematical Sciences, University of SouthamptonSouthampton, United Kingdom Institute for Complex Systems Simulation, University of SouthamptonSouthampton, United Kingdom Heilbronn Institute, School of Mathematics, University of BristolBristol, United Kingdom Department of Vector Biology, Liverpool School of Tropical MedicineLiverpool, United Kingdom Estonian Genome Center, University of TartuTartu, Estonia Department of Biology, Pennsylvania State UniversityUniversity Park, PA, United States Wellcome Trust Sanger InstituteHinxton, United Kingdom Department of Zoology, University of CambridgeCambridge, United Kingdom Centre for GeoGenetics, Natural History Museum of Denmark, University of CopenhagenCopenhagen, Denmark Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of DenmarkKongens Lyngby, Denmark Medical Research Council Metabolic Diseases Unit, Department of Clinical Biochemistry, University of Cambridge and Institute of Metabolic ScienceCambridge, United Kingdom Department of Evolutionary Biology, Institute of Molecular and Cell Biology, University of TartuTartu, Estonia Estonian BiocentreTartu, Estonia Estonian Academy of SciencesTallinn, Estonia Institute of Biological Problems of the North, Russian Academy of SciencesMagadan, Russian Federation |
format |
Article in Journal/Newspaper |
author |
Clemente, Florian J. Cardona, Alexia Inchley, Charlotte E. Peter, Benjamin M. Jacobs, Guy Pagani, Luca Lawson, Daniel John 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 Arendt Rendt Rasmussen, Simon B. Willerslev, Eske Vidal-Puig, Antonio J. Tyler-Smith, Chris Villems, Richard Nielsen, Rasmus Wedel Metspalu, Mait Malyarchuk, Boris A. Derenko, Miroslava V. Kivisild, Toomas |
spellingShingle |
Clemente, Florian J. Cardona, Alexia Inchley, Charlotte E. Peter, Benjamin M. Jacobs, Guy Pagani, Luca Lawson, Daniel John 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 Arendt Rendt Rasmussen, Simon B. Willerslev, Eske Vidal-Puig, Antonio J. Tyler-Smith, Chris Villems, Richard Nielsen, Rasmus Wedel Metspalu, Mait Malyarchuk, Boris A. Derenko, Miroslava V. 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 John 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 Arendt Rendt Rasmussen, Simon B. Willerslev, Eske Vidal-Puig, Antonio J. Tyler-Smith, Chris Villems, Richard Nielsen, Rasmus Wedel Metspalu, Mait Malyarchuk, Boris A. Derenko, Miroslava V. 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 |
Elsevier BV |
publishDate |
2014 |
url |
http://hdl.handle.net/10754/563835 https://doi.org/10.1016/j.ajhg.2014.09.016 |
genre |
Arctic Arctic Greenland inuits |
genre_facet |
Arctic Arctic Greenland inuits |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225582 Clemente, F. J., Cardona, A., Inchley, C. E., Peter, B. M., Jacobs, G., Pagani, L., … Kivisild, T. (2014). A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations. The American Journal of Human Genetics, 95(5), 584–589. doi:10.1016/j.ajhg.2014.09.016 doi:10.1016/j.ajhg.2014.09.016 00029297 The American Journal of Human Genetics PMC4225582 25449608 http://hdl.handle.net/10754/563835 |
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 |
_version_ |
1786809101442875392 |
spelling |
ftkingabdullahun:oai:repository.kaust.edu.sa:10754/563835 2023-12-31T10:02:08+01:00 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 John 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 Arendt Rendt Rasmussen, Simon B. Willerslev, Eske Vidal-Puig, Antonio J. Tyler-Smith, Chris Villems, Richard Nielsen, Rasmus Wedel Metspalu, Mait Malyarchuk, Boris A. Derenko, Miroslava V. Kivisild, Toomas Biological and Environmental Sciences and Engineering (BESE) Division Bioscience Program Integrative Systems Biology Lab Department of Archaeology and Anthropology, University of CambridgeCambridge, United Kingdom Department of Integrative Biology, University of California, BerkeleyBerkeley, CA, United States Mathematical Sciences, University of SouthamptonSouthampton, United Kingdom Institute for Complex Systems Simulation, University of SouthamptonSouthampton, United Kingdom Heilbronn Institute, School of Mathematics, University of BristolBristol, United Kingdom Department of Vector Biology, Liverpool School of Tropical MedicineLiverpool, United Kingdom Estonian Genome Center, University of TartuTartu, Estonia Department of Biology, Pennsylvania State UniversityUniversity Park, PA, United States Wellcome Trust Sanger InstituteHinxton, United Kingdom Department of Zoology, University of CambridgeCambridge, United Kingdom Centre for GeoGenetics, Natural History Museum of Denmark, University of CopenhagenCopenhagen, Denmark Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of DenmarkKongens Lyngby, Denmark Medical Research Council Metabolic Diseases Unit, Department of Clinical Biochemistry, University of Cambridge and Institute of Metabolic ScienceCambridge, United Kingdom Department of Evolutionary Biology, Institute of Molecular and Cell Biology, University of TartuTartu, Estonia Estonian BiocentreTartu, Estonia Estonian Academy of SciencesTallinn, Estonia Institute of Biological Problems of the North, Russian Academy of SciencesMagadan, Russian Federation 2014-11 http://hdl.handle.net/10754/563835 https://doi.org/10.1016/j.ajhg.2014.09.016 unknown Elsevier BV http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225582 Clemente, F. J., Cardona, A., Inchley, C. E., Peter, B. M., Jacobs, G., Pagani, L., … Kivisild, T. (2014). A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations. The American Journal of Human Genetics, 95(5), 584–589. doi:10.1016/j.ajhg.2014.09.016 doi:10.1016/j.ajhg.2014.09.016 00029297 The American Journal of Human Genetics PMC4225582 25449608 http://hdl.handle.net/10754/563835 Article 2014 ftkingabdullahun https://doi.org/10.1016/j.ajhg.2014.09.016 2023-12-02T20:22:44Z 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. This research was supported by European Research Council Starting Investigator grant FP7-261213 to T.K. C.T.-S., Y.X., Q.A., and M.S. were supported by Wellcome Trust grant 098051, and T.A. was supported by Wellcome Trust grant WT100066MA. M. Metspalu and R.V. received supported from the European Union European Regional Development Fund Centre of Excellence in Genomics to the Estonian Biocentre. T.K, M. Metspalu, and R.V. were supported by Estonian Institutional Research grant IUT24-1, and M. Metspalu received Estonian Science Foundation grant 8973. Article in Journal/Newspaper Arctic Arctic Greenland inuits King Abdullah University of Science and Technology: KAUST Repository The American Journal of Human Genetics 95 5 584 589 |