CoChat
Sign Up
Cited by 411Genetic diversity and population structureEvolution and Genetic DynamicsGenetic and phenotypic traits in livestock

Population genomics reveal recent speciation and rapid evolutionary adaptation in polar bears

Open access
Liu, Shiping, Lorenzen, Eline D., Fumagalli, Matteo, Li, Bo, Harris, Kelley, Xiong, Zijun, Zhou, Long, Korneliussen, Thorfinn Sand +21 more·2014·Cell
DOI 10.1016/j.cell.2014.03.054PMC PMC4089990
Open this paper in CoChat — free accountOpen PDF

Abstract

SUMMARY Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyperlipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479–343 thousand years BP. We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears; nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease, implying important reorganization of the cardio-vascular system. One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL); functional mutations in APOB may explain how polar bears are able to cope with life-long elevated LDL levels that are associated with high risk of heart disease in humans.

AI snapshot

Written from the paper’s full text.

TL;DR

Population genomic analysis of 89 polar bear and brown bear genomes estimates that the species diverged only 479–343 thousand years ago and finds stronger positive selection on the polar bear lineage, especially in cardiovascular, lipid-metabolism, and pigmentation genes. The authors argue that polar bears rapidly adapted to a hyperlipid marine diet and Arctic life, with APOB and other cardiomyopathy/vascular genes as key candidates.

Key findings

  • Polar bears and brown bears diverged c. 479–343 kya, a much more recent estimate than some prior genomic studies; the authors conclude polar bears likely emerged closer to the lower bound because genotyping errors inflate divergence-time estimates.
  • Polar bears have smaller long-term effective population sizes and fewer private SNPs (2.6 million) than brown bears (7.7 million), with slower linkage disequilibrium decay.
  • Gene flow was inferred mainly from polar bears into North American brown bears after divergence, with an estimated migration rate of 0.0018% genetic replacement per generation; admixture blocks were at most 1.1 Mbp, suggesting an old event.
  • Nine of the top 16 genes under strong positive selection in polar bears are related to heart function in humans, including APOB; APOB had a fixed-to-polymorphic mutation ratio of 1:2 in polar bears versus 1:162 in brown bears, an 80-fold reduction, and nine fixed missense mutations in polar bears, five clustering in the N-terminal βα1 domain (binomial p = 0.029).
  • Two pigmentation candidate genes, LYST and AIM1, showed strong positive selection; LYST contained seven polar bear-specific missense substitutions versus one in brown bear.

Methods

  • The study deep-sequenced and de novo assembled a polar bear reference genome at 101X, then resequenced 18 polar bears and 10 brown bears at ~22X and an additional 61 polar bears at ~3.5X, totaling 89 complete genomes.
  • Joint demographic history and divergence time were inferred using an identity-by-state (IBS) tract method and ∂a∂i, both incorporating past population size changes; gene flow was assessed with IBS tracts, ∂a∂i, and D statistics/ABBA-BABA.
  • Selection scans analyzed coding regions of 19,822 genes with the giant panda as outgroup, using a homogeneity test, Hudson-Aguade-Kreitman test, Fst estimation, and a method accounting for genotype-call uncertainty; candidate genes were then subjected to enrichment analyses.

Limitations

  • The paper states it could not confidently estimate the timing of the polar bear bottleneck or confidently infer when admixture took place; the IBS tract method has limited power to detect migration very close to divergence.
  • The paper notes limited brown bear sampling and that none of the brown bear samples came from regions where polar and brown bears are currently sympatric, where recently admixed individuals would be most likely.
  • The paper states that a lack of appropriate functional studies prevented direct identification of causal variants, so functional impact was assessed by computational prediction.
  • The text also makes evident that selection analyses used ranked outlier lists rather than simulation-based p-values from specific demographic models, and that variation in sample size and effective population size may only partly explain the stronger selection signal in polar bears.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.cell.2014.03.054

Cites

118 of 118 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 31 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease.

    “nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease”
    Quote in the paperSubstantial claim
  • Findingown data

    Genes on the polar bear lineage have been under stronger positive selection than in brown bears.

    “We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears;”
    • Also stated in: § Genes under positive selection in polar bears · hedged
      “In general, we also find evidence of more positive selection acting on the polar bear lineage than on the brown bear lineage.”
    Quote in the paperSubstantial claim
  • Findingown data

    Prior to divergence, there was a 10-fold decline in the global joint ancestral population.

    “Prior to divergence, we find a 10-fold decline in the global joint ancestral population (Table S3).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Polar bears declined in population size after the split from brown bears.

    “Polar bears declined in population size after the split from brown bears, although we were unable to confidently estimate the timing of the bottleneck.”
    Quote in the paperSubstantial claim
  • Findingown data

    Polar bears and brown bears diverged only about 479-343 thousand years ago.

    “We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479–343 thousand years BP.”
    • Also stated in: § The age of the polar bear as a species · hedged
      “Both approaches indicated that the two species diverged only c. 479–343 kya (Fig. 2A, Table S3).”
    Quote in the paperSubstantial claim
  • May combine two claims. 20
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 23

  • May combine two claims.

    Findingown data

    The population size decrease in polar bears was either of greater magnitude or of longer duration than in brown bears.

    “both the IBS tract method and ∂a∂i indicate that the population size decrease in polar bears was either of a greater magnitude or of a longer duration than in brown bears”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Polar bears show a slower rate of linkage disequilibrium decay than brown bears.

    “we find a slower rate of LD decay in polar bears (Fig. S3A).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The number of private SNPs in polar bears is 2.6 million, about one third of the 7.7 million in brown bears.

    “the number of private SNPs in polar bears (2.6 million, Fig. S1B) is about one third of that in brown bears (7.7 million, Fig. S1C).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    There is evidence of recent migration between brown bear populations.

    “In addition, we find evidence of recent migration between brown bear populations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Using ∂a∂i, non-zero migration is observed in both directions, but the migration rate is substantially higher in the polar-to-brown bear direction.

    “we observe non-zero migration in both directions, but infer a substantially higher migration rate in the polar-to-brown bear direction (Table S3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The strongest evidence of gene flow between polar bears and brown bears is with ABC Islands brown bears, and the weakest is with North American and Fennoscandian brown bear populations.

    “The strongest evidence is found with brown bears from the ABC Islands and the weakest with brown bear populations from North America and Fennoscandia”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    APOB is ranked second using the homogeneity test score and has an Fst ranking in the top 3% of the empirical distribution.

    “The gene is ranked second using our homogeneity test score, has an Fst ranking in the top 3% of the empirical distribution”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The ratio of fixed-to-polymorphic mutations in the polar bear APOB lineage is 1:2, compared with 1:162 in the brown bear lineage, an 80-fold reduction.

    “the ratio of fixed-to-polymorphic mutations in the polar bear lineage is 1:2, compared with 1:162 in the brown bear lineage—an 80-fold reduction.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Five of the nine fixed missense mutations cluster within the N-terminal βα1 domain of APOB, although the region comprises only 22% of the protein (binomial test p-value = 0.029).

    “Five of the nine cluster within the N-terminal βα1 domain of the APOB gene, although the region comprises only 22% of the protein (binomial test p-value = 0.029).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Three polar bear changes in LYST are located in proximity to the N-terminal structural domain, and map close to human mutations associated with Chediak-Higashi syndrome, a hair and eyes depigmentation disease.

    “Three polar bear changes in LYST are located in proximity to the N-terminal structural domain, and map close to human mutations associated with Chediak-Higashi syndrome, a hair and eyes depigmentation disease (Fig. 5C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    A majority of the top genes under positive selection in polar bears have functions related to the cardiovascular system and most of them to cardiomyopathy.

    “We find it remarkable that a majority of the top genes under positive selection in polar bears have functions related to the cardiovascular system and most of them to cardiomyopathy, in particular when considering their divergence from brown bears no more than c. 479–343 kya.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    LYST contains seven polar bear-specific missense substitutions, in contrast to only one in brown bear.

    “LYST contains seven polar bear-specific missense substitutions, in contrast to only one in brown bear.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    APOB encodes the primary lipoprotein component of low-density lipoprotein (LDL).

    “One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL);”
    • Also stated in: § Genes associated with adipose tissue development and fatty acid metabolism · plain
      “which produces apolipoprotein B (apoB), the primary lipid-binding protein of chylomicrons and low-density lipoproteins (LDL) (Whitfield et al., 2004).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Whitfield et al., 2004 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Admixture between polar bears and brown bears was an old event, with enough time having passed for recombination to break up long introgressed DNA stretches.

    “Hence the limited length of admixture blocks supports the hypothesis that admixture was an old event, and that enough time has passed for recombination to break up the long stretches of introgressed DNA.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    ApoB enables the transport of fat molecules in blood plasma and lymph and acts as a ligand for LDL receptors, facilitating movement of molecules such as cholesterol into cells.

    “ApoB enables the transport of fat molecules in blood plasma and lymph and acts as a ligand for LDL receptors, facilitating the movement of molecules such as cholesterol into cells (Benn, 2009).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Benn, 2009 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In humans, elevated cholesterol levels are a major risk factor for the development of cardiovascular disease.

    “in humans, elevated cholesterol levels are a major risk factor for the development of cardiovascular disease (Cannon et al., 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cannon et al., 2010 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The data support a scenario of polar bears evolving rapidly and being under strong positive selection following divergence from brown bears.

    “Overall, our data support a scenario of polar bears evolving rapidly and being under strong positive selection following the divergence from brown bears.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In humans and mice, genetic APOB variants associated with increased levels of apoB are also associated with unusually high plasma concentrations of cholesterol and LDL, which contribute to hypercholesterolemia and heart disease in humans.

    “In humans and mice, genetic APOB variants associated with increased levels of apoB are also associated with unusually high plasma concentrations of cholesterol and LDL, which in turn contribute to hypercholesterolemia and heart disease in humans (Benn, 2009; Hegele, 2009).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Benn, 2009 source

      Not checked in the free run.

    • cites Hegele, 2009 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    APOB produces apolipoprotein B (apoB), the primary lipid-binding protein of chylomicrons and low-density lipoproteins (LDL).

    “which produces apolipoprotein B (apoB), the primary lipid-binding protein of chylomicrons and low-density lipoproteins (LDL) (Whitfield et al., 2004).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Whitfield et al., 2004 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Mutations in TTN are associated with familial dilated cardiomyopathy in humans.

    “mutations in TTN are associated with familial dilated cardiomyopathy (Herman et al., 2012).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Herman et al., 2012 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    XIRP1 is associated with the development of cardiac muscle cells.

    “XIRP1, also known as Cardiomyopathy-associated protein 1, is associated with the development of cardiac muscle cells (van der Ven et al., 2006).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites van der Ven et al., 2006 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Potentially important re-organization of the cardiovascular system has taken place in polar bears since their divergence from brown bears, which may be related to polar bear ecology.

    “Based on this evidence, we argue that potentially important re-organization of the cardiovascular system has taken place in polar bears since their divergence from brown bears, which may be related to polar bear ecology.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    ALPK3 plays a role in cardiomyocyte differentiation.

    “ALPK3 encodes a kinase and plays a role in cardiomyocyte differentiation; knockout genes in mice show both hypertrophic and dilated forms of cardiomyopathy (Van Sligtenhorst et al., 2012).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Van Sligtenhorst et al., 2012 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    CUL7 plays a role in vascular morphogenesis.

    “CUL7 plays a role in vascular morphogenesis (Arai et al., 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Arai et al., 2003 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    EHD3 plays a role in endocytic transport.

    “EHD3 encodes a class of cardiac trafficking proteins and plays a role in endocytic transport (Galperin et al., 2002).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Galperin et al., 2002 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Defects in VCL are associated with dilated cardiomyopathy in humans.

    “Defects in VCL are associated with dilated cardiomyopathy in humans (Olson et al., 2002).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Olson et al., 2002 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Melanosomes, where melanin production occurs, are lysosome-related organelles and have been implicated in the progression of disease associated with Lyst mutation in mice.

    “Melanosomes, where melanin production occurs, are lysosome-related organelles and have been implicated in the progression of disease associated with Lyst mutation in mice (Trantow et al., 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Trantow et al., 2010 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Regulation of EHD3 plays a role in a molecular pathway related to heart failure.

    “Regulation of EHD3 plays a role in a molecular pathway related to heart failure (Gudmundsson et al., 2012).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Gudmundsson et al., 2012 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    ABCC6 is associated with premature atherosclerosis.

    “ABCC6 is associated with transport of molecules across membranes and is associated with premature atherosclerosis (Trip et al., 2002)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Trip et al., 2002 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Chronically elevated serum cholesterol, particularly LDL, contribute to the degenerative accumulation of plaques in the arteries, which can lead to progressive narrowing or blocking of blood vessels.

    “Chronically elevated serum cholesterol, particularly LDL, contribute to the degenerative accumulation of plaques in the arteries, which can lead to progressive narrowing or blocking of blood vessels (Klop et al., 2013).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Klop et al., 2013 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    ARID5B is involved in pathogenesis of atherosclerosis and adipogenesis.

    “ARID5B is involved in pathogenesis of atherosclerosis and adipogenesis (Wang et al., 2012).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wang et al., 2012 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Several methods (IBS tract, ∂a∂i, D statistics) were used to fully elucidate patterns of gene flow between polar and brown bear populations since their divergence.

    “To fully elucidate patterns of gene flow between polar and brown bear populations since their divergence, we used several methods: (i) the IBS tract method; (ii) ∂a∂i; and (iii) D statistics, also known as the ABBA-BABA test (Durand et al., 2011; Green et al., 2010) (Extended Experimental Procedures Section Gene Flow and Introgression).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Durand et al., 2011 source

      Not checked in the free run.

    • cites Green et al., 2010 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    Several complementary approaches were used to investigate evolutionary changes in protein sequences, analyzing the coding regions of 19,822 genes with the giant panda genome as an outgroup.

    “We used several complementary approaches to investigate evolutionary changes in protein sequences and analyzed the coding regions of 19,822 genes annotated across the polar bear and brown bear samples, using the giant panda genome sequence (Li et al., 2009) as an outgroup (Extended Experimental Procedures Section Positive Selection).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Li et al., 2009

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Data were filtered with a dedicated pipeline that removed low quality reads and sites showing unusual coverage, base quality score bias, strand bias, and deviation from Hardy-Weinberg Equilibrium.

    “We filtered data with a dedicated pipeline and removed low quality reads as well as sites showing unusual coverage compared to the empirical distribution, base quality score bias (p < 1e-5), strand bias (p < 1e-5), and deviation from Hardy-Weinberg Equilibrium (p < 1e-3) (Extended Experimental Procedures Section Data Generation and QC Measures).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationown data

    Our study reveals the strength of using a population genomic approach to resolve the evolutionary history of a non-model organism in terms of divergence time, demographic history, selection and adaptation.

    “Our study reveals the strength of using a population genomic approach to resolve the evolutionary history of a non-model organism in terms of divergence time, demographic history, selection and adaptation.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Lyst-mutant phenotypes in cattle, mice, rats and mink are characterized by hypopigmentation, a melanosome defect characterized by light coat colour.

    “The types and positions of mutations identified in LYST vary widely, but Lyst-mutant phenotypes in cattle, mice, rats and mink are characterized by hypopigmentation, a melanosome defect characterized by light coat colour (Kunieda et al., 1999; Runkel et al., 2006; Gutiérrez-Gil et al., 2007).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Kunieda et al., 1999 source

      Not checked in the free run.

    • cites Runkel et al., 2006 source

      Not checked in the free run.

    • cites Gutiérrez-Gil et al., 2007 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    Two approaches were applied to estimate reliably when polar bears and brown bears diverged, both incorporating past population size changes.

    “We applied two approaches to estimate reliably when polar bears and brown bears diverged. Importantly, both methods incorporate past population size changes.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The scaffold N50 size of the polar bear reference genome was c. 16 Mb.

    “The scaffold N50 size of the genome was c. 16 Mb (http://dx.doi.org/10.5524/100008).”
    Quote in the paperNot a substantial claim
38 of 38

  • The authors state this as an assumption.

    The average generation time of polar bears is 11.35 years.

    “Assuming an average generation time of 11.35 years (Cronin et al., 2009; De Barba et al., 2010)”

  • The paper relies on this without support.

    The N-terminal βα1 domain of APOB encodes the surface region and contains the majority of functional domains for lipid transport.

    “This domain encodes the surface region and contains the majority of functional domains for lipid transport.”

  • The paper relies on this without support.

    A white phenotype is usually selected against in natural environments, but is common in the Arctic, where it likely confers a selective advantage.

    “A white phenotype is usually selected against in natural environments, but is common in the Arctic (e.g. beluga whale, arctic hare and arctic fox), where it likely confers a selective advantage.”

  • The paper relies on this without support.

    The white fur is caused by a lack of pigment in the hair.

    “The white fur is one of the most distinctive features of the species and is caused by a lack of pigment in the hair.”

  • The paper relies on this without support.

    LYST encodes the lysosomal trafficking regulator Lyst.

    “LYST encodes the lysosomal trafficking regulator Lyst.”

  • The paper relies on this without support.

    Such a drastic genetic response to chronically elevated levels of fat and cholesterol in the diet has not previously been reported.

    “Such a drastic genetic response to chronically elevated levels of fat and cholesterol in the diet has not previously been reported.”
6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Liu, S., Lorenzen, E. D., Fumagalli, M., Li, B., Harris, K., Xiong, Z., Zhou, L., Korneliussen, T. S., Somel, M., Babbitt, C., Wray, G., Li, J., He, W., Wang, Z., Fu, W., Xiang, X., Morgan, C. C., Doherty, A., O’Connell, M. J., McInerney, J. O., Born, E. W., Dalén, L., Dietz, R., Orlando, L., Sonne, C., Zhang, G., Nielsen, R., Willerslev, E., & Wang, J.
Affiliations
  • BGI Group (China) (CN)
  • University of Copenhagen (DK)
  • University of California, Berkeley (US)
  • Duke University (US)
  • Dublin City University (IE)
  • National University of Ireland, Maynooth (IE)
  • Grønlands Naturinstitut (GL)
  • Swedish Museum of Natural History (SE)
  • Aarhus University (DK)
Corresponding author
  • Nielsen, Rasmus
  • Willerslev, Eske
  • Wang, Jun
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2014-05
Volume
157
Issue
4
Pages
785-794
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2014.03.054
PMC
PMC4089990
OpenAlex
W2164299185
Semantic Scholar
5b5eb572470613e5cfe88478ebca1259916cf090
Cited by
411
References
118
Citations by year
2026: 21 · 2025: 26 · 2024: 25 · 2023: 29 · 2022: 28 · 2021: 40 · 2020: 55 · 2019: 37 · 2018: 33 · 2017: 40 · 2016: 29 · 2015: 35 · 2014: 13
FWCI
25.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
  • PubMed Central (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
  • eScholarship (California Digital Library) (submittedVersion)
  • Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
  • OpenMETU (Middle East Technical University) (submittedVersion, cc-by-nc-nd)
  • Repository@Nottingham (University of Nottingham) (submittedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion)
  • Griffith Research Online (submittedVersion)
Funders
  • European Commission (253376)
  • Lundbeckfonden (R109-2012-9995, R70-2010-6286, R155-2013-16338, R38-2008-3048, R24-2008-2527)
  • Museum of the North, University of Alaska
  • U.S. Public Health Service (2R14003229-07)
  • National Human Genome Research Institute (R01HG003229)
  • National Institute of General Medical Sciences (P50GM081883)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
Keywords
polar bear, brown bear, speciation, positive selection, cardiovascular adaptation, cardiomyopathy, apolipoprotein B, low-density lipoprotein, hyperlipidemia, marine mammal diet, population genomics
MeSH terms
Adaptation, Physiological, Adipose Tissue, Animals, Apolipoproteins B, Arctic Regions, Ursidae, Biological Evolution, Fatty Acids, Genetics, Population, Genome, Gene Flow

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review