BACKGROUND: Patterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations. RESULTS: 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. CONCLUSIONS: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.

This work was supported in part by a Russian Ministry of Science Mega-grant (no 11.G34.31.0068), a St. Petersburg State University grant (no 1.50.1623.2013), an ICREA grant (no. BFU2014-55090-P), an EMBO YIP 2013 grant (no. BFU2015-7116-ERC) and an MICINN grant (no. BFU2015-6215-ERC). Sample collection and validation of reproductive genes were performed under the permit number 1833/2013, granted by the Namibian Ministry of Environment and Tourism