Skip to main content
Premium Trial:

Request an Annual Quote

Cheetah Genome Harbors Low Levels of Diversity, Gives Glimpse into Evolutionary Past

NEW YORK (GenomeWeb) — The genome of the African cheetah, Acinonyx jubatus, gives a peek into how the endangered cat came to lose much of its genetic diversity.

An international team of researchers sequenced the genome of a wild-born Namibian cheetah — named Chewbaaka — to 75X coverage, and the genomes of three Tanzanian and three other Namibian cheetahs to lower coverage. As the team reported in Genome Biology this week, the cheetah genome exhibits a loss of genomic diversity, and retains echoes of two population bottlenecks — one about 100,000 years ago, and the other approximately 12,000 years ago. It has also accumulated an excess of non-synonymous variation in certain genes, which could contribute to its poor reproductive success rate.

"Overall, the cheetah genome offers unparalleled insight into the history, adaptation, and survival of a treasured endangered species," the team, led by Stephen O'Brien from Saint Petersburg State University in Russia and Nova Southeastern University in Florida, wrote in its paper.

O'Brien and his colleagues aligned the reads they obtained from Chewbaaka to the domestic cat reference genome as well as to the lion, tiger, and domestic dog genomes. Using that genome and the other, lower-coverage cheetah genomes, the researchers examined the level of genetic diversity in cheetah using a range of measures.

They reported, for instance, that cheetahs have the lowest genome-wide SNV incidence among nearly a dozen species, including humans, domestic cats, gorillas, lions, and Tasmanian devils. In addition, as compared to the genomes of feral domestic cats, the cheetah genomes have longer homozygous stretches, and they harbor far fewer heterozygous SNV sites than other organisms — 85 percent fewer sites than the domestic cat genome and 70 percent less than the human genome.

Overall, the team wrote, the cheetah has lost 90 percent to 99 percent of the level of variation that's observed in other, outbred mammals.

Because cheetahs can accept reciprocal skin allografts from unrelated individuals as if they were their own, O'Brien and his colleagues also examined their major histocompatibility complex, a cluster of about 280 immune-related genes.

Using the domestic cat assembly as a guide, they resolved 178 genes belonging to class II, extended class II, class I, and extended class I. They noted that though most classes were well covered, certain class I MHC genes couldn't be found.

Overall, though, the order and structure of the cheetah MHC genes were highly similar to that of the domestic cat MHC genes, though differed from that of human and dog MHC genes.

The cheetah MHC genes also exhibited a decreased number of SNVs as compared to domestic cats, wildcats, humans, and dogs, though was similar to that of Cinnamon, the highly inbred Abyssinian cat sequenced in 2007.

O'Brien and his colleagues also used these patterns of sequence variation to model and infer the population history of cheetahs. The researchers used a software tool to compare the expected allele frequency and the observed allele frequency spectrum by calculating a composite likelihood score for potential scenarios, and homed in on a case in which an expanding ancestral population divided into two bottlenecked populations.

The model showed the first bottleneck around the time when some studies have suggested that cheetahs migrated out of North America to Asia via the Bering Sea land bridge. Other studies, however, suggest an Asian origin for cheetahs, placing the migration around the Asia-to-Africa dispersal. A more recent bottleneck, at the time of the late Pleistocene extinction of large animals like mammoths, dire wolves, and saber-toothed tigers, further reduced variation in both cheetah populations.

Both of these bottlenecks, the researchers wrote, would have increased incestuous mating and reduced endemic variability.

Additional analysis based on a pairwise sequential Markovian coalescent algorithm also indicated decreasing cheetah population size for the last 100,000 years.

Present-day cheetahs, O'Brien and his colleagues noted, suffer from a number of traits linked to inbreeding: they have difficulty reproducing, even when captive, and ejaculate from male cheetahs has an average of 80 percent malformed spermatozoa.

By comparing reproduction-linked genes in cheetah, cat, tiger, dogs, and humans, the researchers found that those from cheetahs had a higher accumulation of non-synonymous mutations. Ninety-two genes had elevated non-synonymous to synonymous mutation ratios, and 18 of those genes had damaging mutations previously linked to dysfunctions in sperm or egg formation.

One gene in particular, AKAP4, accumulated potentially damaging mutations at a high rate, mutations not seen in the tiger, domestic cat, or wildcat orthologs. AKAP4 is expressed in the testes, and its homologs are a key part of sperm development and onset of spermatozoan aberration in other mammals.

The five homozygous function-damaging mutations in this gene, the researchers said, could account for the elevated pleiomorphic sperm in every cheetah.

"In concert with ecological, habitat restoration, and other conservation issues, the cheetah's genetic disposition should be useful in efforts to sustain and increase cheetah population numbers in their present and former ranges," O'Brien and his colleagues wrote.

The Scan

Steps for Quick Review

The US Food and Drug Administration is preparing for the quick review of drugs and vaccines for the Omicron variant, according to the Wall Street Journal.

Moving Away From Using Term 'Race'

A new analysis finds that geneticists are using the term "race" in their papers less than in years past, as Science reports.

Point of the Program

The Guardian writes that some scientists have called the design of a UK newborn sequencing program into question.

Science Papers Present Multi-Omic Analysis of Lung Cells, Regulation of Cardiomyocyte Proliferation

In Science this week: a multi-omic analysis of lung cells focuses on RIT1-regulated pathways, and more.