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Cited by 971High Altitude and HypoxiaGenetic and phenotypic traits in livestockGenomics and Phylogenetic Studies

The yak genome and adaptation to life at high altitude

Open access
Qiu, Qiang, Zhang, Guojie, Ma, Tao, Qian, Wubin, Wang, Junyi, Ye, Zhiqiang, Cao, Changchang, Hu, Quanjun +41 more·2012·Nature Genetics
DOI 10.1038/ng.2343
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Abstract

Domestic yaks (Bos grunniens) provide meat and other necessities for Tibetans living at high altitude on the Qinghai-Tibetan Plateau and in adjacent regions. Comparison between yak and the closely related low-altitude cattle (Bos taurus) is informative in studying animal adaptation to high altitude. Here, we present the draft genome sequence of a female domestic yak generated using Illumina-based technology at 65-fold coverage. Genomic comparisons between yak and cattle identify an expansion in yak of gene families related to sensory perception and energy metabolism, as well as an enrichment of protein domains involved in sensing the extracellular environment and hypoxic stress. Positively selected and rapidly evolving genes in the yak lineage are also found to be significantly enriched in functional categories and pathways related to hypoxia and nutrition metabolism. These findings may have important implications for understanding adaptation to high altitude in other animal species and for hypoxia-related diseases in humans.

AI snapshot

Written from the paper’s full text.

TL;DR

The paper reports a draft genome of a female domestic yak and comparative analyses with cattle that identify gene-family expansions and positively selected genes enriched in hypoxia response, sensory perception, and energy/nutrition metabolism. These findings suggest genomic signatures of high-altitude adaptation in yak and may inform understanding of hypoxia-related disease in humans.

Key findings

  • The yak genome assembly was generated at 65-fold coverage, with total length 2,657 Mb, contig N50 20.4 kb, scaffold N50 1.4 Mb, and 22,282 predicted protein-coding genes.
  • Yak had 2.2 million heterozygous SNVs and a heterozygosity rate of 0.89 × 10⁻³, about 1.5 times higher than the estimated cattle rate of 0.59 × 10⁻³.
  • Yak-specific gene families were significantly over-represented in olfactory sensation (14 genes; P < 0.01) and host defense/immunity (11 genes; P < 0.01); 596 gene families were substantially expanded in yak, enriched for sensory perception and energy metabolism.
  • Yak had more GPCR transmembrane domains than cattle (1,558 versus 1,358), and the hypoxia-associated Hig_1_n domain had 13 copies in yak versus 9 in cattle.
  • Among 8,923 high-confidence yak-cattle-human orthologs, 85 positively selected genes were identified in yak and 95 in cattle; 3 of 81 hypoxia-response genes (3.7%) showed positive selection in yak versus none in cattle (P < 0.05).

Methods

  • Whole-genome shotgun sequencing of a female domestic yak from Huangyuan County, Qinghai Province, China, living above 3,700 m, using Illumina HiSeq 2000 with multiple insert-size libraries; assembly used SOAPdenovo.
  • RNA-seq from heart, liver, brain, stomach, and lung tissues plus six Sanger-sequenced fosmid clones were used to assess assembly completeness and annotate genes via homology, ab initio prediction, and RNA-seq evidence.
  • Comparative analyses included gene-family expansion/contraction, conserved synteny, Ka/Ks estimation, and branch-site likelihood ratio tests for positive selection across yak, cattle, human, and other mammals.

Limitations

  • The paper states no explicit limitations section.
  • Evident from the text: the genome is a draft assembly from a single female domestic yak, and yak chromosomes lacked physical maps, so chromosomal assignments relied on homology.
  • The paper notes that further understanding may require functional analysis of candidate genes in comparative stress studies; the reported adaptive signals are genomic and statistical rather than experimentally validated.

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

Integrity signals

Registry

Crossref · 10.1038/ng.2343

Cites

70 of 70 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

17 of 36 cited sources checked · 6 supported · 0 flagged · accuracy not yet measured

  • Findingcitation

    High coverage permitted the identification of 2.2 million heterozygous single-nucleotide variants (SNVs) within the sequenced individual.

    “High coverage 11,12 permitted the identification of 2.2 million heterozygous single-nucleotide variants (SNVs) within the sequenced individual (Supplementary Figs. 5 and 6 and Supplementary Tables 7 and 8).”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [11] Li, R. et al. SNP detection for massively parallel whole-genome resequencing. Genome Res. 19, 1124–1132 (2009). source
    • cites [12] Wang, J. et al. The diploid genome sequence of an Asian individual. Nature 456, 60–65 (2008). source

      The SNP and indel identification section reports 3.07 million SNPs in the sequenced YH genome, and the Depth effect section says increased sequencing depth reduced SNP-calling errors. The Haplotype analysis section identifies 700,320 heterozygotes overlapping HapMap loci and another 1,021,953 heterozygous SNPs absent from HapMap; our copy does not support the claimed figure of 2.2 million heterozygous SNVs. No page numbers are available in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
  • Findingcitation

    The heterozygosity rate of the sequenced yak was 0.89 × 10^-3, approximately 1.5 times higher than that estimated for cattle (0.59 × 10^-3).

    “The heterozygosity rate (0.89 × 10 -3 ) was approximately 1.5 times higher than that estimated for cattle (0.59 × 10 -3 ) (refs.10,13).”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [10] Elsik, C.G. et al. The genome sequence of taurine cattle: a window to ruminant biology and evolution. Science 324, 522–528 (2009). source

      The cattle-genome assembly passage (section labelled Abstract; page unavailable) discusses SNP mapping accuracy, not a heterozygosity estimate. Searches for “0.59,” “heterozygosity rate,” and heterozygous sites found no passage in our copy giving the cattle value or the stated comparison with yak. (LLM, conf=0.73)

      Experimental — accuracy not yet measured
    • cites [13] Wade, C.M. et al. Genome sequence, comparative analysis, and population genetics of the domestic horse. Science 326, 865–867 (2009). source

      The horse genome paper’s Abstract discusses horse SNPs and compares some horse findings with bovine findings, but does not report a yak heterozygosity rate. Searches for yak heterozygosity and the stated cattle rate found neither the 0.89 × 10^-3 nor the 0.59 × 10^-3 estimate in our copy. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
  • Findingown data

    TreeFam identified 13,810 homologous gene families shared by yak, cattle, human and dog.

    “First, we used TreeFam 20 to identify 13,810 homologous gene families shared by 4 species (yak, cattle, human and dog):”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [20] Li, H. et al. TreeFam: a curated database of phylogenetic trees of animal gene families. Nucleic Acids Res. 34, D572–D580 (2006). source
  • Findingown data

    Using the human genome as an outgroup, 207 conserved ancestral homologous synteny blocks (aHSBs) were reconstructed, covering 2.51 Gb (94%) of the yak genome.

    “Using the human genome as an outgroup, we reconstructed 207 conserved ancestral homologous synteny blocks (aHSBs) 16 covering 2.51 Gb (94%) of the yak genome.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [16] Larkin, D.M. et al. Breakpoint regions and homologous synteny blocks in chromosomes have different evolutionary histories. Genome Res. 19, 770–777 (2009). source

      The Identification of HSBs section describes defining homologous synteny blocks using the human genome as a reference, supporting the methodological connection. It does not describe human as an outgroup or report 207 ancestral blocks covering 2.51 Gb (94%) of a yak genome; yak is not among the genomes analyzed. No page number is available in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Findingown data
    § The yak genome and adaptation to life at high altitude

    Positively selected and rapidly evolving genes in the yak lineage are significantly enriched in functional categories and pathways related to hypoxia and nutrition metabolism.

    “Positively selected and rapidly evolving genes in the yak lineage are also found to be significantly enriched in functional categories and pathways related to hypoxia and nutrition metabolism.”
    • Also stated in: § l e t t e r s · plain
      “The PSGs detected in yak were enriched for genes involved in the hypoxia response and energy metabolism (Supplementary Tables 15 and 16).”
    • Also stated in: § l e t t e r s · plain
      “we found five key genes that show signs of positive selection in yak nutrition pathways (Fig. 3c)”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The single sequenced female domestic yak is representative of the domestic yak species for genomic comparisons and inferences about adaptation to high altitude.
  • Classified as probably not a substantial claim. 15
  • May combine two claims. 26

  • Classified as probably not a substantial claim.

    Premisecitation
    § The yak genome and adaptation to life at high altitude

    Genomic comparisons between closely related species provide insights into the genetic basis of mammalian divergence and adaptation.

    “Genomic comparisons between closely related species provide insights into the genetic basis of mammalian divergence and adaptation 8,9 .”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [8] Kosiol, C. et al. Patterns of positive selection in six mammalian genomes. PLoS Genet. 4, e1000144 (2008). source
    • cites [9] Chimpanzee Sequencing and Analysis Consortium. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437, 69–87 (2005). source

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

    Findingown data
    § The yak genome and adaptation to life at high altitude

    The yak draft assembly total length of 2,657 Mb is close to the 2,649 Mb of sequence obtained for the cattle genome (UMD 3.1).

    “with a total length of 2,657 Mb, close to the 2,649 Mb of sequence obtained for the cattle genome 10 (UMD 3.1)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [10] Elsik, C.G. et al. The genome sequence of taurine cattle: a window to ruminant biology and evolution. Science 324, 522–528 (2009). source

      The assembly passage (section labeled Abstract; page unavailable) confirms that the paper reports a sequenced cattle genome, but it discusses Btau3.1 and Btau4.0, not UMD 3.1. It gives an estimated genome size of 2.87 Gbp and does not substantiate the cited figure of 2,649 Mb of sequence. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

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

    Interpretationcitation

    The higher heterozygosity in yak may be due to a longer and more systematic selection in cattle and/or to introgression from wild yaks still living on the Qinghai-Tibetan Plateau.

    “This may be due to a longer and more systematic selection in cattle and/or to introgression from wild yaks still living on the Qinghai-Tibetan Plateau 14,15 .”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [14] Wang, Z. et al. Phylogeographical analyses of domestic and wild yaks based on mitochondrial DNA: new data and reappraisal. J. Biogeogr. 37, 2332–2344 (2010). source

      The Phylogeographical structure section (page unavailable) says that domestic yaks were sometimes hybridized with wild yaks, supporting the proposed introgression. It does not compare yak and cattle heterozygosity or say that cattle underwent longer, more systematic selection. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [15] Guo, S. et al. Origin of mitochondrial DNA diversity of domestic yaks. BMC Evol. Biol. 6, 73 (2006). source

      The 'Domestication of yaks in the Qinghai-Tibetan Plateau' section (page unavailable) suggests that some domestic-yak lineages may reflect later introgression from wild yaks, which supports one proposed explanation. It does not compare yak and cattle heterozygosity or attribute a difference to longer, more systematic selection in cattle; its evidence concerns mitochondrial haplotype diversity. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Study design and conductown data
    § The yak genome and adaptation to life at high altitude

    The sequencing depth of 98% of the assembly was more than 20-fold, ensuring high accuracy at the nucleotide level.

    “The sequencing depth of 98% of the assembly was more than 20-fold (Supplementary Fig. 1), ensuring high accuracy at the nucleotide level 11 .”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [11] Li, R. et al. SNP detection for massively parallel whole-genome resequencing. Genome Res. 19, 1124–1132 (2009). source

      The Abstract (page unavailable) reports high nucleotide-call accuracy in a deep human resequencing dataset, and the Discussion (page unavailable) describes the method as measuring accuracy at each nucleotide position. But the reported 98% refers to coverage of genotyped autosomal sites, not the proportion of an assembly sequenced at more than 20-fold depth. Our copy does not substantiate that depth figure. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    Yak and cattle were estimated to have diverged approximately 4.9 million years ago, comparable to the time at which humans and chimpanzees diverged.

    “Yak and cattle were estimated to have diverged approximately 4.9 million years ago, which is comparable to the time at which humans and chimpanzees diverged 9 (Supplementary Fig. 12).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [9] Chimpanzee Sequencing and Analysis Consortium. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437, 69–87 (2005). source

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

    Premisecitation

    Frequent turnover of gene copy and/or protein domain number has been proposed as a major mechanism underlying the adaptive divergence of closely related species.

    “Frequent turnover of gene copy and/or protein domain number has been proposed as a major mechanism underlying the adaptive divergence of closely related species 9,[17][18][19] .”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [9] Chimpanzee Sequencing and Analysis Consortium. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437, 69–87 (2005). source

      The gene-evolution discussion (page unavailable in our copy) describes gene-family expansion, recent human-specific duplications, and genes deleted in chimpanzees, supporting the gene-copy-change portion of the claim. It does not identify turnover of protein-domain number or propose that these changes are a major mechanism of adaptive divergence. (LLM, conf=0.77)

      Experimental — accuracy not yet measured
    • cites [17][18][19]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

    Premisecitation

    Adam17 and Arg2 proteins affect Hif-1α stability and activity by regulating production of tumor necrosis factor α (TNF-α) and nitric oxide, respectively, whereas Mmp3 has key roles in numerous physiological processes.

    “The Adam17 and Arg2 proteins affect Hif-1α stability and activity by regulating production of tumor necrosis factor α (TNF-α) 31,32 and nitric oxide, respectively 33,34 , whereas Mmp3 has key roles in numerous physiological processes 35 .”
    Quote in the paperNot a substantial claim2 of 5 sources checked
    • cites [31] Srour, N. et al. TACE/ADAM-17 maturation and activation of sheddase activity require proprotein convertase activity. FEBS Lett. 554, 275–283 (2003). source

      The Introduction (page not available) identifies ADAM17/TACE as an enzyme that cleaves TNF-α into a soluble form. Section 3.5 reports that inhibiting TACE processing reduces TNF-α release. The paper does not establish the attributed effect on HIF-1α stability or activity; the Arg2 and Mmp3 clauses carry separate citations. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [32] Zhou, J., Schmid, T. & Brune, B. Tumor necrosis factor–α causes accumulation of a ubiquitinated form of hypoxia inducible factor-1α through a nuclear factor-κB–dependent pathway. Mol. Biol. Cell 14, 2216–2225 (2003). source
    • cites [33] Sogawa, K. et al. Inhibition of hypoxia-inducible factor 1 activity by nitric oxide donors in hypoxia. Proc. Natl. Acad. Sci. USA 95, 7368–7373 (1998). source
    • cites [34] Sousa, M.S., Latini, F.R., Monteiro, H.P. & Cerutti, J.M. Arginase 2 and nitric oxide synthase: pathways associated with the pathogenesis of thyroid tumors. Free Radic. Biol. Med. 49, 997–1007 (2010). source

      The Discussion and Fig. 3 (page unavailable) report that ARG2 knockdown reduced HIF-1 expression in thyroid carcinoma cells; the Discussion also links ARG2 inhibition to increased nitric oxide production. The paper does not establish that nitric oxide mediates an effect on HIF-1α protein stability or activity. The Adam17 and Mmp3 clauses are assigned to other citations, not this source. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [35] Rosenberg, G.A. Matrix metalloproteinases and their multiple roles in neurodegenerative diseases. Lancet Neurol. 8, 205–216 (2009). source

  • May combine two claims.

    Premisecitation

    In their high-altitude environments, yaks must not only maintain normal energy production under hypoxic pressure but must also optimize nutritional assimilation, as a consequence of the limited herbal resources available.

    “In their high-altitude environments, yaks must not only maintain normal energy production under hypoxic pressure 7,37 but must also optimize nutritional assimilation, as a consequence of the limited herbal resources available 1 .”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [7] Wang, H. et al. Comparison of nitrogen metabolism in Yak (Bos grunniens) and indigenous cattle (Bos taurus) on the Qinghai-Tibetan Plateau. Asian-Aust. J. Anim. Sci. 24, 766–773 (2011). source
    • cites [37] Han, X.T. et al. Effects of high altitude and season on fasting heat production in the yak Bos grunniens or Poephagus grunniens. Br. J. Nutr. 88, 189–197 (2002). source
    • cites [1] Wiener, G., Han, J.L. & Long, R.J. The Yak 2nd edn. (Regional Office for Asia and the Pacific Food and Agriculture Organization of the United Nations, Bangkok, 2003).

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Findingown data
    § The yak genome and adaptation to life at high altitude

    Approximately 90% of the total sequence was covered by 2,083 scaffolds of >307 kb, with the largest scaffold spanning 8.8 Mb.

    “Approximately 90% of the total sequence was covered by 2,083 scaffolds of >307 kb, with the largest scaffold spanning 8.8 Mb.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § The yak genome and adaptation to life at high altitude

    The yak draft assembly had contig N50 of 20.4 kb and scaffold N50 of 1.4 Mb.

    “and contig and scaffold N50 sizes of 20.4 kb and 1.4 Mb, respectively (Supplementary Table 2).”
    Quote in the paperNot a substantial claim

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

    Findingown data
    § The yak genome and adaptation to life at high altitude

    The assembly metrics of the yak genome were comparable to those of other animal genome assemblies generated by next-generation sequencing technology.

    “The assembly metrics of the yak genome were comparable to those of other animal genome assemblies generated by next-generation sequencing technology (Supplementary Table 3).”
    Quote in the paperNot a substantial claim

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

    Findingown data
    § The yak genome and adaptation to life at high altitude

    GC content distributions of the yak genome were similar to those of the cattle genome.

    “GC content distributions were similar to those of the cattle genome (Supplementary Fig. 3 and Supplementary Note).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Using the branch-site likelihood ratio test, 85 positively selected genes (PSGs) were identified in yak and 95 PSGs in cattle.

    “We identified 85 PSGs (in yak) and 95 PSGs (in cattle) (Fig. 3b and Supplementary Table 14).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Overall, yak and cattle genes were highly similar, with 45% of encoded proteins identical and mean protein similarity approximating 99.5%.

    “Overall, yak and cattle genes were highly similar, with 45% of encoded proteins identical and mean protein similarity approximating 99.5% (Supplementary Figs. 9 and 10).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Average synonymous (Ks) and nonsynonymous (Ka) gene divergence values between yak and cattle were 0.0114 and 0.00207, respectively, close to the values between human and chimpanzee genes.

    “Average synonymous (Ks) and nonsynonymous (Ka) gene divergence values between yak and cattle were 0.0114 and 0.00207, respectively, close to the values between human and chimpanzee genes (Supplementary Fig. 11).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Phylogenetic analysis of genes encoding the Hig_1_n domain showed an expansion in the numbers of closely related Hig_1_n domains in both yak and cattle, as well as three additional copies in yak.

    “Phylogenetic analysis of genes that encoded this domain showed an expansion in the numbers of the closely related Hig_1_n domains in both yak and cattle, as well as three additional copies in yak (Fig. 2b).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    8,923 high-confidence 1:1:1 orthologous genes were identified in the yak, cattle and human genomes, most of which also correspond to genes in the horse, dog, mouse and chimpanzee genomes.

    “We identified 8,923 high-confidence 1:1:1 orthologous genes in the yak, cattle and human genomes, most of which also correspond to genes in the horse, dog, mouse and chimpanzee genomes (Supplementary Fig. 8).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The yak-specific gene families contained 170 genes, 75 of which have known InterPro domains.

    “The yak-specific gene families contained 170 genes, 75 of which have known InterPro domains.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    362 gene families were specific to yak and cattle, and 100 were found only in yak.

    “362 gene families were specific to yak and cattle, and 100 were found only in yak (Fig. 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Of 81 genes examined in the response to hypoxia functional category (GO 0001666), 3 (3.7%) showed evidence of positive selection in yak (compared to none in cattle), which is significantly higher than the background level of positive selection across the genome (P < 0.05).

    “Of 81 genes examined in the response to hypoxia functional category (GO 0001666), 3 (3.7%)showed evidence of positive selection in yak (compared to none in cattle), which is significantly higher than the background level of positive selection across the genome (P < 0.05) (Fig. 3b).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Gene family expansions in yak were significantly enriched for cytochrome-c oxidase activity (GO 0004129, P < 0.01) and ATP synthesis coupled proton transport (GO 0015986, P < 0.01).

    “and energy metabolism (GO 0004129, cytochrome-c oxidase activity, P < 0.01; GO 0015986, ATP synthesis coupled proton transport, P < 0.01) (Supplementary Table 11).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Gene family expansions in yak were significantly enriched for olfactory receptor activity (GO 0004984, P < 0.01) and sensory perception of taste (GO 0050909, P < 0.01).

    “Functional categories that were enriched for significant gene family expansions mainly included sensory perception (gene ontology (GO) 0004984, olfactory receptor activity, P < 0.01; GO 0050909, sensory perception of taste, P < 0.01)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data
    § The yak genome and adaptation to life at high altitude

    The genome assembly covered, without any obvious errors in assembly, 97% of 6 fosmids sequenced by Sanger sequencing and 98% of 81,020 Unigenes assembled from Illumina RNA sequencing data for 5 tissues, indicating coverage of most of the euchromatic regions.

    “The genome assembly covered, without any obvious errors in assembly, 97% of 6 fosmids sequenced by Sanger sequencing and 98% of 81,020 Unigenes assembled from Illumina RNA sequencing (RNAseq) data for 5 tissues (Supplementary Fig. 2 and Supplementary Tables 4 and 5), indicating coverage of most of the euchromatic regions.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Yak and cattle both have 30 chromosomes and have similar karyotypes.

    “Yak and cattle both have 30 chromosomes and have similar karyotypes 1 , which allows chromosomal assignments on the basis of homology, despite a lack of physical maps for yak chromosomes.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] Wiener, G., Han, J.L. & Long, R.J. The Yak 2nd edn. (Regional Office for Asia and the Pacific Food and Agriculture Organization of the United Nations, Bangkok, 2003).

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

    Interpretationreasoning
    § The yak genome and adaptation to life at high altitude

    These findings may have important implications for understanding adaptation to high altitude in other animal species and for hypoxia-related diseases in humans.

    “These findings may have important implications for understanding adaptation to high altitude in other animal species and for hypoxia-related diseases in humans.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The single sequenced female domestic yak is representative of the domestic yak species for genomic comparisons and inferences about adaptation to high altitude.

  • May combine two claims.

    Premisecitation
    § The yak genome and adaptation to life at high altitude

    Yaks have numerous anatomical and physiological traits that equip them for life at high altitude, including large lungs and hearts, lack of hypoxic pulmonary vasoconstriction, increased foraging ability, strong environmental sense and high energy metabolism.

    “Yaks have numerous anatomical and physiological traits that equip them for life at high altitude, including large lungs and hearts 1 , lack of hypoxic pulmonary vasoconstriction 5 , increased foraging ability 6 , strong environmental sense 1 and high energy metabolism 1,7 .”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [1] Wiener, G., Han, J.L. & Long, R.J. The Yak 2nd edn. (Regional Office for Asia and the Pacific Food and Agriculture Organization of the United Nations, Bangkok, 2003).

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [5] Dolt, K.S. et al. cDNA cloning, gene organization and variant specific expression of HIF-1α in high altitude yak (Bos grunniens). Gene 386, 73–80 (2007). source
    • cites [6] Shao, B. et al. Morphological adaptations of yak (Bos grunniens) tongue to the foraging environment of the Qinghai-Tibetan Plateau. J. Anim. Sci. 88, 2594–2603 (2010). source

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

    Interpretationreasoning

    The identification of genes required for natural high-altitude adaptation may help to improve current understanding, treatment and prevention of altitude sickness and other hypoxia-related diseases in humans.

    “The identification of genes required for natural high-altitude adaptation may help to improve current understanding, treatment and prevention of altitude sickness and other hypoxia-related diseases in humans.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Hif-1α triggers wide transcription of genes involved in angiogenesis, vasodilatation and energy metabolism.

    “As a master regulator of the cellular response to hypoxia, Hif-1α triggers wide transcription of genes involved in angiogenesis, vasodilatation and energy metabolism [30][31][32][33][34][35] .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30][31][32][33][34][35]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

    Study design and conductown data

    RNA integrity number (RIN) values of the RNA samples ranged from 8.6 to 10.0, with no sign of degradation.

    “their RNA integrity number (RIN) values ranged from 8.6-10.0,with no sign of degradation.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Libraries that gave reads unevenly distributed among gene regions were discarded and replaced.

    “Libraries that gave reads that were unevenly distributed among the gene regions (for example, showing a strong bias toward 5′ or 3′ regions) were discarded and replaced.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    This report of the yak genome sequence, together with the many SNVs identified, will facilitate genetic dissection of agronomically important traits in the species and will accelerate the genetic improvement of milk and meat production in this animal.

    “In addition, this report of the yak genome sequence, together with the many SNVs identified, will facilitate genetic dissection of agronomically important traits in the species and will accelerate the genetic improvement of milk and meat production in this animal that is essential to the lifestyle and economy of the Tibetan people.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Alleles of human ADAM17 were previously shown to be present at significantly different frequencies in Tibetans and low-altitude dwellers, indicating a possible role for this gene in altitude adaptation.

    “Notably, alleles of human ADAM17 were previously shown to be present at significant different frequencies in Tibetans and low-altitude dwellers 36 , indicating a possible role for this gene in altitude adaptation.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Simonson, T.S. et al. Genetic evidence for high-altitude adaptation in Tibet. Science 329, 72–75 (2010). source

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

    Study design and conductown data

    The sequence depth of multiple-copy genes was in the same range as for single-copy genes.

    “The sequence depth of these multiple-copy genes was in the same range as for single-copy genes (Supplementary Fig. 7).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The existence of these blocks confirms the extensive synteny of the cattle and yak genomes and also allows the detection of breakpoint regions.

    “The existence of these blocks confirms the extensive synteny of the cattle and yak genomes and also allows the detection of breakpoint regions (Supplementary Table 9).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Camk2b regulates the secretion of gastric acid in the rumen, which contributes to the assimilation of volatile fatty acids produced by ruminal fermentation; Gcnt3, Hsd17b12, Whsc1 and Glul have important roles in polysaccharide, fatty acid and amino-acid metabolism, respectively.

    “Camk2b regulates the secretion of gastric acid in the rumen, which contributes to the assimilation of volatile fatty acids produced by ruminal fermentation [38][39][40][41][42] , and Gcnt3, Hsd17b12, Whsc1 and Glul have important roles in polysaccharide, fatty acid and amino-acid metabolism, respectively [43][44][45][46] .”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [38][39][40][41][42]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [43][44][45][46]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

35 of 35

  • The paper relies on this without support.

    The single sequenced female domestic yak is representative of the domestic yak species for genomic comparisons and inferences about adaptation to high altitude.

    “Genomic DNA was extracted from the liver of a female yak with an estimated inbreeding coefficient of 0.094 (ref. 1) that lived above 3,700 m in Huangyuan County of Qinghai Province, China.”
    “In this study, we sequenced the genome of a female domestic yak using a whole-genome shotgun strategy and the Illumina HiSeq 2000 platform.”
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Authors
Qiu, Q., Zhang, G., Ma, T., Qian, W., Wang, J., Ye, Z., Cao, C., Hu, Q., Kim, J., Larkin, D. M., Auvil, L., Capitanu, B., Ma, J., Lewin, H. A., Qian, X., Lang, Y., Zhou, R., Wang, L., Wang, K., Xia, J., Liao, S., Pan, S., Lu, X., Hou, H., Wang, Y., Zang, X., Yin, Y., Ma, H., Zhang, J., Wang, Z., Zhang, Y., Zhang, D., Yonezawa, T., Hasegawa, M., Zhong, Y., Liu, W., Zhang, Y., Huang, Z., Zhang, S., Long, R., Yang, H., Wang, J., Lenstra, J. A., Cooper, D. N., Wu, Y., Wang, J., Shi, P., Wang, J., & Liu, J.
Affiliations
  • Lanzhou University (CN)
  • BGI Group (China) (CN)
  • University of Illinois Urbana-Champaign (US)
  • Fudan University (CN)
  • Utrecht University (NL)
  • University of Copenhagen (DK)
  • Kunming Institute of Zoology (CN)
  • Sichuan University (CN)
Corresponding author
  • Shi, Peng
  • Liu, Jianquan
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2012-07-01
Volume
44
Issue
8
Pages
946-949
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/ng.2343
OpenAlex
W2149716668
Cited by
971
References
70
Citations by year
2026: 55 · 2025: 76 · 2024: 87 · 2023: 75 · 2022: 113 · 2021: 108 · 2020: 103 · 2019: 67 · 2018: 67 · 2017: 55 · 2016: 48 · 2015: 36 · 2014: 46 · 2013: 28 · 2012: 5
FWCI
20.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Genetics (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Lanzhou University Institutional Repository (submittedVersion, cc-by-nc)
  • Utrecht University Repository (Utrecht University) (submittedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
National Human Genome Research Institute (R21 HG006464)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › High Altitude and Hypoxia
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
Keywords
yak, high-altitude adaptation, hypoxia, gene family expansion, energy metabolism, positive selection
MeSH terms
Acclimatization, Altitude, Animals, Base Sequence, Cattle, DNA, Female, Multigene Family, Molecular Sequence Data, Phylogeny, Selection, Genetic, Species Specificity, Genome, Evolution, Molecular

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.

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Statistics and arithmetic are recomputed, not judged.

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