Genomic legacy of the African cheetah, Acinonyx jubatus

Abstract

BackgroundPatterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations.ResultsHere 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.ConclusionsThe study provides an unprecedented genomic perspective for the rare cheetah, with potential relevance to the species’ natural history, physiological adaptations and unique reproductive disposition.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0837-4) contains supplementary material, which is available to authorized users.

Continued decline in genetic diversity among wild cheetahs (Acinonyx jubatus) without further loss of semen quality

“…The cheetah's lack of genetic diversity was originally detected by allozyme analysis and the ability of unrelated conspecifics to accept reciprocal skin grafts . This finding was subsequently confirmed by six additional measures of genomic variation (O'Brien, 1994), a lack of diversity in MHC class II-DRB alleles (Castro-Prieto et al, 2011), and the whole-genome sequencing of Namibian and Tanzanian cheetahs (Dobrynin et al, 2015). The cheetah's lack of genetic diversity is attributed to a severe population bottleneck that occurred~12,000 years ago (Driscoll et al, 2002;O'Brien et al, 1985), from which the entire extant species is derived (Charruau et al, 2011).…”

“…A major challenge for the practical use of genome resource banks is the high cryo-sensitivity of oocytes and embryos (Pukazhenthi et al, 2006a), which are particularly important for maintaining mitochondrial and X-linked gene diversity. Intriguingly, recent sequencing of the cheetah genome revealed a high prevalence of mutations in AKAP4 (an X-linked gene involved in sperm motility; (Dobrynin et al, 2015)), highlighting the importance of conserving diversity in sex-linked genes. In circumventing natural selection, assisted reproductive technologies may contribute to the loss of functional alleles for AKAP4 and other genes linked to fertility/fecundity.…”

“…With the recent sequencing of the cheetah genome (Dobrynin et al, 2015), this species presents exciting opportunities to assess the relative importance of heterozygosity versus rare alleles in the conservation of inbred populations. Yet, this flagship species continues to decline in the wild, and its future is uncertain.…”

“…The cheetah's lack of genetic diversity is attributed to a severe population bottleneck that occurred~12,000 years ago (Driscoll et al, 2002;O'Brien et al, 1985), from which the entire extant species is derived (Charruau et al, 2011). Intriguingly, recent genome sequencing suggests that a second ancient bottleneck occurred N 100,000 years ago, coincident with the migration of cheetahs into Africa (Dobrynin et al, 2015). Importantly, the cheetah is the only modern felid species that lacks a non-inbred population -a fact that not only limits conservation options, but also complicates understanding the consequences of reduced genetic diversity (O'Brien and Johnson, 2005).…”

“…Since the early 1980s, captive cheetah populations in North America and Europe have been managed through cooperative breeding programs, with the goals of conserving rare genetic lineages and maintaining 90% of extant genetic diversity for the next 100 years (Association of Zoos and Aquariums, 2014). Given the cheetah's precarious status in the wild, the recent sequencing of its genome (Dobrynin et al, 2015), and the extensive efforts to create captive 'insurance' populations, it is an opportune time to evaluate the relationship between genetic diversity and reproductive traits in this species. We have a unique opportunity to test this relationship because our research group has collected DNA samples and/or reproductive data from N 200 southern African cheetahs over the past 30 years.…”