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Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication

Michael J. Montague, Gang Li, Barbara Gandolfi, Razib Khan, Bronwen L. Aken, Steven M. J. Searle, Patrick Minx, LaDeana W. Hillier, Daniel C. Koboldt, Brian W. Davis, Carlos A. Driscoll, Christina S. Barr, Kevin Blackistone, Javier Quilez, Belen Lorente-Galdos, Tomas Marques-Bonet, Can Alkan, Gregg W. C. Thomas, Matthew W. Hahn, Marilyn Menotti-Raymond, Stephen J. O’Brien, Richard K. Wilson, Leslie A. Lyons, William J. Murphy, and Wesley C. Warren
PNAS December 2, 2014 111 (48) 17230-17235; published ahead of print November 10, 2014 https://doi.org/10.1073/pnas.1410083111
Michael J. Montague
aThe Genome Institute, Washington University School of Medicine, St. Louis, MO 63108;
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  • ORCID record for Michael J. Montague
Gang Li
bDepartment of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843;
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Barbara Gandolfi
cDepartment of Veterinary Medicine & Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65201;
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Razib Khan
dPopulation Health & Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616;
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Bronwen L. Aken
eWellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom;
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Steven M. J. Searle
eWellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom;
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Patrick Minx
aThe Genome Institute, Washington University School of Medicine, St. Louis, MO 63108;
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LaDeana W. Hillier
aThe Genome Institute, Washington University School of Medicine, St. Louis, MO 63108;
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Daniel C. Koboldt
aThe Genome Institute, Washington University School of Medicine, St. Louis, MO 63108;
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Brian W. Davis
bDepartment of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843;
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Carlos A. Driscoll
fNational Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20886;
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Christina S. Barr
fNational Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20886;
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Kevin Blackistone
fNational Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20886;
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Javier Quilez
gCatalan Institution for Research and Advanced Studies, Institute of Evolutionary Biology, Pompeu Fabra University, 08003 Barcelona, Spain;
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Belen Lorente-Galdos
gCatalan Institution for Research and Advanced Studies, Institute of Evolutionary Biology, Pompeu Fabra University, 08003 Barcelona, Spain;
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Tomas Marques-Bonet
gCatalan Institution for Research and Advanced Studies, Institute of Evolutionary Biology, Pompeu Fabra University, 08003 Barcelona, Spain;hCentro de Analisis Genomico 08028, Barcelona, Spain;
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Can Alkan
iDepartment of Computer Engineering, Bilkent University, Ankara 06800, Turkey;
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Gregg W. C. Thomas
jDepartment of Biology, Indiana University, Bloomington, IN 47405;
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Matthew W. Hahn
jDepartment of Biology, Indiana University, Bloomington, IN 47405;
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Marilyn Menotti-Raymond
kLaboratory of Genomic Diversity, Center for Cancer Research, Frederick, MD 21702;
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Stephen J. O’Brien
lDobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199178, Russia; andmOceanographic Center, Nova Southeastern University, Fort Lauderdale, FL 33314
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Richard K. Wilson
aThe Genome Institute, Washington University School of Medicine, St. Louis, MO 63108;
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Leslie A. Lyons
cDepartment of Veterinary Medicine & Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65201;
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  • For correspondence: wwarren@genome.wustl.eduwmurphy@cvm.tamu.edulyonsla@missouri.edu
William J. Murphy
bDepartment of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843;
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  • For correspondence: wwarren@genome.wustl.eduwmurphy@cvm.tamu.edulyonsla@missouri.edu
Wesley C. Warren
aThe Genome Institute, Washington University School of Medicine, St. Louis, MO 63108;
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  • For correspondence: wwarren@genome.wustl.eduwmurphy@cvm.tamu.edulyonsla@missouri.edu
  1. Edited by James E. Womack, Texas A&M University, College Station, TX, and approved October 3, 2014 (received for review June 2, 2014)

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Significance

We present highlights of the first complete domestic cat reference genome, to our knowledge. We provide evolutionary assessments of the feline protein-coding genome, population genetic discoveries surrounding domestication, and a resource of domestic cat genetic variants. These analyses span broadly, from carnivore adaptations for hunting behavior to comparative odorant and chemical detection abilities between cats and dogs. We describe how segregating genetic variation in pigmentation phenotypes has reached fixation within a single breed, and also highlight the genomic differences between domestic cats and wildcats. Specifically, the signatures of selection in the domestic cat genome are linked to genes associated with gene knockout models affecting memory, fear-conditioning behavior, and stimulus-reward learning, and potentially point to the processes by which cats became domesticated.

Abstract

Little is known about the genetic changes that distinguish domestic cat populations from their wild progenitors. Here we describe a high-quality domestic cat reference genome assembly and comparative inferences made with other cat breeds, wildcats, and other mammals. Based upon these comparisons, we identified positively selected genes enriched for genes involved in lipid metabolism that underpin adaptations to a hypercarnivorous diet. We also found positive selection signals within genes underlying sensory processes, especially those affecting vision and hearing in the carnivore lineage. We observed an evolutionary tradeoff between functional olfactory and vomeronasal receptor gene repertoires in the cat and dog genomes, with an expansion of the feline chemosensory system for detecting pheromones at the expense of odorant detection. Genomic regions harboring signatures of natural selection that distinguish domestic cats from their wild congeners are enriched in neural crest-related genes associated with behavior and reward in mouse models, as predicted by the domestication syndrome hypothesis. Our description of a previously unidentified allele for the gloving pigmentation pattern found in the Birman breed supports the hypothesis that cat breeds experienced strong selection on specific mutations drawn from random bred populations. Collectively, these findings provide insight into how the process of domestication altered the ancestral wildcat genome and build a resource for future disease mapping and phylogenomic studies across all members of the Felidae.

  • Felis catus
  • domestication
  • genome

Footnotes

  • ↵1M.J.M. and G.L. contributed equally to this work.

  • ↵2To whom correspondence may be addressed. Email: wwarren{at}genome.wustl.edu, wmurphy{at}cvm.tamu.edu, or lyonsla{at}missouri.edu.
  • Author contributions: M.J.M., G.L., B.G., L.A.L., W.J.M., and W.C.W. designed research; M.J.M., G.L., B.G., P.M., L.W.H., D.C.K., B.W.D., C.A.D., C.S.B., K.B., G.W.C.T., M.W.H., M.M.-R., S.J.O., L.A.L., W.J.M., and W.C.W. performed research; M.J.M., G.L., B.G., B.L.A., S.M.J.S., D.C.K., B.W.D., C.A.D., J.Q., B.L.-G., T.M.-B., C.A., G.W.C.T., M.W.H., R.K.W., L.A.L., W.J.M., and W.C.W. contributed new reagents/analytic tools; M.J.M., G.L., B.G., R.K., B.W.D., J.Q., B.L.-G., T.M.-B., C.A., G.W.C.T., M.W.H., L.A.L., W.J.M., and W.C.W. analyzed data; and M.J.M., G.L., B.G., R.K., P.M., D.C.K., B.W.D., C.A.D., C.S.B., K.B., T.M.-B., M.W.H., L.A.L., W.J.M., and W.C.W. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. GU270865.1, KJ923925–KJ924979, SRX026946, SRX026943, SRX026929, SRX027004, SRX026944, SRX026941, SRX026909, SRX026901, SRX026955, SRX026947, SRX026911, SRX026910, SRX026948, SRX026928, SRX026912, SRX026942, SRX026930, SRX026913, SRX019549, SRX019524, SRX026956, SRX026945, and SRX026960).

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1410083111/-/DCSupplemental.

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Cat genome and domestication signals
Michael J. Montague, Gang Li, Barbara Gandolfi, Razib Khan, Bronwen L. Aken, Steven M. J. Searle, Patrick Minx, LaDeana W. Hillier, Daniel C. Koboldt, Brian W. Davis, Carlos A. Driscoll, Christina S. Barr, Kevin Blackistone, Javier Quilez, Belen Lorente-Galdos, Tomas Marques-Bonet, Can Alkan, Gregg W. C. Thomas, Matthew W. Hahn, Marilyn Menotti-Raymond, Stephen J. O’Brien, Richard K. Wilson, Leslie A. Lyons, William J. Murphy, Wesley C. Warren
Proceedings of the National Academy of Sciences Dec 2014, 111 (48) 17230-17235; DOI: 10.1073/pnas.1410083111

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Cat genome and domestication signals
Michael J. Montague, Gang Li, Barbara Gandolfi, Razib Khan, Bronwen L. Aken, Steven M. J. Searle, Patrick Minx, LaDeana W. Hillier, Daniel C. Koboldt, Brian W. Davis, Carlos A. Driscoll, Christina S. Barr, Kevin Blackistone, Javier Quilez, Belen Lorente-Galdos, Tomas Marques-Bonet, Can Alkan, Gregg W. C. Thomas, Matthew W. Hahn, Marilyn Menotti-Raymond, Stephen J. O’Brien, Richard K. Wilson, Leslie A. Lyons, William J. Murphy, Wesley C. Warren
Proceedings of the National Academy of Sciences Dec 2014, 111 (48) 17230-17235; DOI: 10.1073/pnas.1410083111
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