Cited by 351Genetic and phenotypic traits in livestockHuman-Animal Interaction StudiesGenetic Mapping and Diversity in Plants and Animals

The DOI matches its Crossref record; 80 of the 80 references it cites were found in a registry or an index; 2 of the 47 sources its claims cite were checked for support.

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

Open access

Abstract

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.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This paper presents a high-quality domestic cat reference genome (FelCat5) and comparative genomic analyses identifying signatures of selection related to carnivory, sensory biology, and domestication. It also reports two recessive KIT missense mutations associated with the Birman gloving pigmentation pattern.

Key findings

  • The FelCat5 assembly comprises 2.35 Gb assigned to all 18 autosomes and the X chromosome, plus 11 Mb in unplaced scaffolds, with an N50 contig of 20.6 kb and scaffold N50 of 4.7 Mb; the cat genome is predicted to contain 19,493 protein-coding genes and 1,855 noncoding RNAs.
  • Genome-wide dN/dS analyses identified 467, 331, and 281 genes putatively under positive selection in the carnivore, felid, and domestic cat (Felinae) ancestral lineages, respectively; Felinae positively selected genes were enriched for lipid metabolism, and sensory genes included vision and hearing candidates.
  • Cats and dogs show an evolutionary tradeoff in chemosensory repertoires: felids have smaller functional olfactory receptor repertoires (~700 genes) than dogs (>800), while the vomeronasal V1r repertoire is reduced in dogs (8 functional genes) but expanded in the cat ancestor (21 functional genes).
  • Domestication analyses found 130 autosomal regions with pooled heterozygosity 4 SDs below the mean or FST greater than 4 SDs from the mean; five high-confidence regions contained neural/neural-crest-related genes (reported as 13 genes in Results and 12 known genes in Fig. 3/conclusion). For Birman gloving, two adjacent KIT exon 6 missense mutations were concordant with the phenotype; all 150 Birman cats genotyped were homozygous for both SNPs, and the Birman gloving haplotype frequency was 12.3% in Ragdoll and 10% in the random nonbreed population.

Methods

  • A female Abyssinian cat (“Cinnamon”) provided DNA for ~14× whole-genome shotgun coverage using Sanger and 454 technology; a BAC library was constructed and end-sequenced, and sequences were assembled with CABOG.
  • Selection analyses used 10,317 sets of 1:1:1:1:1 orthologs from human, cow, dog, tiger, and domestic cat, with PAML 4.0 branch and branch-site models, TreeSAAP and PROVEAN for amino acid impact, and WebGestalt for functional enrichment.
  • Domestication scans used pooled resequencing of 22 domestic cats from six breeds (~58× coverage) and a wildcat pool of two European and two Near Eastern wildcats (~7× coverage); SNVs were called with SAMtools, VarScan 2, and PoPoolation2, and 100-kb windows with 50-kb step were tested for low Hp and high FST. KIT exons were resequenced/genotyped in 409 cats from 21 breeds, 5 Birman outcrosses, and 315 random bred cats, with a larger sample of 150 Birman cats and 729 additional cats.

Limitations

  • The paper states that the selection inferences “call for additional functional analyses,” so most positively selected genes are computational candidates rather than experimentally validated.
  • The paper notes cats are considered only semidomesticated, with ongoing admixture with wildcats, a relatively short cohabitation history, and limited isolation from wild populations, which may explain the modest number of strong domestication signals.
  • Evident from the text: domestication scans rely on pooled sequencing and pooled breed samples, the wildcat comparison uses only four individuals at ~7× coverage, and the reported gene count in the five high-confidence regions differs between the Results (13 genes) and Fig. 3/conclusion (12 known genes).

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Integrity signals

Registry

Crossref · 10.1073/pnas.1410083111

Cites

80 of 80 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

33 Not checked yet · 26 Own result · 9 Own interpretation · 3 Own method · 2 Partly supported · 2 No basis given · accuracy not yet measured

Verify all 45 references — free account

Show all 43 claims

  • It may state two separate claims as one. 21
  • Probably not a substantial claim. 17
32 of 32
  • The paper relies on this without support.

    Most of the 30-40 cat breeds originated recently, within the past 150 y, largely due to selection for aesthetic rather than functional traits.

    “Unlike many other domesticated mammals bred for food, herding, hunting, or security, most of the 30-40 cat breeds originated recently, within the past 150 y, largely due to selection for aesthetic rather than functional traits.”
  • The paper relies on this without support.

    Visual acuity is adaptive for hunting and catching prey, especially for crepuscular predators such as the cat and other carnivores.

    “Visual acuity is adaptive for hunting and catching prey, especially for crepuscular predators such as the cat and other carnivores.”
  • The paper relies on this without support.

    Gene duplication and gene loss events often play substantial roles in phenotypic differences between species.

    “Gene duplication and gene loss events often play substantial roles in phenotypic differences between species.”
  • The paper relies on this without support.

    Two extensive chemosensory gene families, coding for olfactory (Or) and vomeronasal (V1r) receptors, are responsible for small-molecule detection of odorants and other chemicals for mediating pheromone perception, respectively.

    “Two extensive chemosensory gene families, coding for olfactory (Or) and vomeronasal (V1r) receptors, are responsible for smallmolecule detection of odorants and other chemicals for mediating pheromone perception, respectively.”
  • The paper relies on this without support.

    Birman cats have a white gloving pattern on their paws.

    “The paws of the Birman breed (Top Left) are distinguished by white gloving.”
  • The paper relies on this without support.

    MYO7A expression is associated with hearing and vision.

    “MYO7A (*) expression is associated with hearing and vision.”
  • The authors state this as an assumption.

    The species tree topology for the selection analysis is (((cat, tiger), dog), cow, human).

    “We tested for signatures of natural selection assuming the species tree topology (((cat, tiger), dog), cow, human).”
7 of 7

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Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

1 of 1

Citations

Cites

Show all 79 references

Research works printed but not linked: 4

  1. ; American Pet Product Manufacturing Association National Pet Owner’s Survey (Am Pet Prod Manuf Assoc, Greenwich, CT, 2008).
  2. RJG Savage, Evolution in carnivorous mammals. Palaeontology 20, 237–271 (1977).
  3. RF Ewer The Carnivores (Cornell Univ Press, New York, 1973).
  4. VA David, , Endogenous retrovirus insertion in the KIT oncogene determines white and white spotting in domestic cats. G3 (Bethesda), 2014).

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Metadata

Authors
Montague, M. J., Li, G., Gandolfi, B., Khan, R., Aken, B. L., Searle, S. M. J., Minx, P., Hillier, L. W., Koboldt, D. C., Davis, B. W., Driscoll, C. A., Barr, C. S., Blackistone, K., Quilez, J., Lorente-Galdos, B., Marques-Bonet, T., Alkan, C., Thomas, G. W. C., Hahn, M. W., Menotti-Raymond, M., O’Brien, S. J., Wilson, R. K., Lyons, L. A., Murphy, W. J., & Warren, W. C.
Affiliations
  • Washington University in St. Louis (US)
  • Texas A&M University (US)
  • University of Missouri (US)
  • University of California, Davis (US)
  • Wellcome Sanger Institute (GB)
  • National Institutes of Health (US)
  • Institució Catalana de Recerca i Estudis Avançats (ES)
  • Catalan Institution for Research and Advanced Studies, Institute of Evolutionary Biology, Pompeu Fabra University, 08003 Barcelona, Spain;
  • Bilkent University (TR)
  • Indiana University Bloomington (US)
  • Frederick National Laboratory for Cancer Research (US)
  • St Petersburg University (RU)
Venue
Proceedings of the National Academy of Sciences
Published
2014-11-10
Volume
111
Issue
48
Pages
17230-17235
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2069681519
Cited by
340
References
79
Citations by year
2026: 20 · 2025: 12 · 2024: 28 · 2023: 28 · 2022: 49 · 2021: 34 · 2020: 27 · 2019: 46 · 2018: 28 · 2017: 24 · 2016: 24 · 2015: 20
FWCI
14.85
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • NSUWorks (Nova Southeastern University) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • OakTrust (Texas A&M University Libraries) (submittedVersion)
  • Bilkent University Institutional Repository (Bilkent University) (submittedVersion)
  • Zenodo (CERN European Organization for Nuclear Research)
Funders
  • U.S. Department of Veterans Affairs (CDA 10-014)
  • Wellcome Trust (095908)
  • National Institutes of Health (R24OD010928)
  • Biotechnology and Biological Sciences Research Council (BB/I025506/1, BB/I025360/2)
  • National Human Genome Research Institute (U54HG003079)
  • National Center for Research Resources (R24RR016094)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Human-Animal Interaction Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
Keywords
positive selection, lipid metabolism, olfactory receptor genes, vomeronasal receptor genes, pheromone detection, domestication syndrome, cat breeds
MeSH terms
Adaptation, Physiological, Amino Acid Sequence, Animals, Animals, Domestic, Animals, Wild, Cats, Chromosome Mapping, Dogs, Female, Male, Molecular Sequence Data, Phylogeny, Selection, Genetic, Species Specificity, Genome, Gene Deletion, Sequence Homology, Amino Acid, Sequence Analysis, DNA, Gene Duplication, Genomics, Membrane Transport Proteins, DNA Copy Number Variations, Carnivory

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