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Dobrynin, P.; Liu, S.; Tamazian, G.; Xiong, Z.; Yurchenko, A.A.; Krasheninnikova, K.; Kliver, S.; Schmidt-KĀntzel, A.; Koepfli, K.-P.; Johnson, W.; Kuderna, L.F.K.; Garcia-Perez, R.; de Manuel, M.; Godinez, R.; Komissarov, A.; Makunin, A.; Brukhin, V.; Qiu, W.; Zhou, L.; Li, F.; Jian, Y.; Driscoll, C.; Antunes, A.; Oleksyk, T.K.; Eizirik, E.; Perelman, P.; Roelke, M.; Wildt, D.; Diekhans, M.; Marques-Bonet, T.; Marker, L.L.; Bhak, J.; Wang, J.; Zhang, G.; O'Brien, S.J.
Genomic legacy of the African cheetah, _Acinonyx jubatus_
2015  Genome Biology (16): 1-19

Patterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations. Here the genome sequence of wild-born African cheetahs reveals extreme genomic depletion in SNV incidence, SNV density, SNVs of coding genes, MHC class I and II genes, and mitochondrial DNA SNVs. Cheetah genomes are on average 95 % homozygous compared to the genomes of the outbred domestic cat (24.08 % homozygous), Virunga Mountain Gorilla (78.12 %), inbred Abyssinian cat (62.63 %), Tasmanian devil, domestic dog and other mammalian species. Demographic estimators impute two ancestral population bottlenecks: one >100,000 years ago coincident with cheetah migrations out of the Americas and into Eurasia and Africa, and a second 11,084-12,589 years ago in Africa coincident with late Pleistocene large mammal extinctions. MHC class I gene loss and dramatic reduction in functional diversity of MHC genes would explain why cheetahs ablate skin graft rejection among unrelated individuals. Significant excess of non-synonymous mutations in AKAP4 (p<0.02), a gene mediating spermatozoon development, indicates cheetah fixation of five function-damaging amino acid variants distinct from AKAP4 homologues of other Felidae or mammals; AKAP4 dysfunction may cause the cheetah's extremely high (>80 %) pleiomorphic sperm. The study provides an unprecedented genomic perspective for the rare cheetah, with potential relevance to the species' natural history, physiological adaptations and unique reproductive disposition.

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