Cheetah genome shows a cat with nine lives

Cheetahs may be one of nature’s great survivors.

A new study this week found that the world’s fastest cat has managed to overcome two population bottlenecks over tens of thousands of years that could have led to its extinction.

By sequencing the cheetah’s genome, an international team writing in the journal Genome Biology concluded that the first one came 100,000 years ago when Acinonyx jubatus first migrated out of North American across the Beringian landbridge to Asia and then eventually south to Africa. This was a time when all the Pleistocene megafauna went extinct, including sabretooths, mammoths and the woolly rhino.

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The second bottleneck came around 10,000-12,000 years ago, further reducing its numbers and causing a major reduction in the gene pool that remains today.

“It was an extinction event in North America and a near extinction among the survivors that already made it to Asia,” Stephen J. O'Brien, a co-author on the study and a chief scientific officer at the Theodosius Dobzhansky Center for Genome Bioinformatics at St. Petersburg State University, told

“Both of these represent a dropping of population size to such low numbers that their genome diversity reflects it,” he said. “It allows you to say wow, there was an event that probably was a brush with extinction – I mean the tigers had one about 75,000 years ago when there was an eruption of some volcano in Southeast Asia.”

To understand its evolutionary history, researchers that also included members of the Beijing Genomics Institute and the Cheetah Conservation Fund (CCF) sequenced the genome from a male Namibian cheetah named 'Chewbaaka', and six other wild cheetahs from Tanzania and Namibia.

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What they found was troubling.

The cheetah’s genome was in poor shape, resulting in elevated rates of juvenile mortality and the extreme abnormalities in sperm development and increases vulnerability to infectious disease outbreaks. The variation in the cheetah genome is far below that observed in inbred dogs and cats, with researchers showing that the cheetah has lost 90-99 percent of the genetic variation typically seen in outbred mammals.

“The cheetahs themselves look as if they were deliberately inbred because the amount of variation they have overall throughout the entire genome is really off the scale as far as being lower than anything else we have ever seen,” O’Brien said. “The cheetah is like the winner of the lowest variation of a natural population. To get down that low, you have to drop down to numbers that are so low that you start inbreeding with close relatives - even though you have an instinctive avoidance of it - because there is nothing else to breed with it.”

A total of 18 cheetah genes showed damaging mutations and one gene in particular, AKAP4, showed a large number of mutations. This can harm sperm development and may explain why cheetahs have a large proportion of defective sperm, and hence low reproductive success.

“There are a handful of genes involved in reproduction that have been clearly disarmed or dismantled,” O’Brien said,” noting that most cat species have only 30 percent of sperm malformed while the cheetah has around 80 percent.

“The gene (AKAP4) … is known in humans and mice to being a very important gene and it’s only expressed in testis and it’s only involved in making proper sperm,” he said. “So, if you knock it out in other species, you end up with malformed sperm and that is what we got in cheetahs.”

But the cheetah’s genome wasn’t completely flawed. The researchers also found genes that demonstrated just why the cheetah has evolved to be the Usain Bolt of the African savannah.

“There are regions that are good, regions that show remarkably fast evolution,” O’Brien said. “That is the signal of natural selection and adaptation and those regions include genes involved with energy metabolism, stress response and are probably associated with the development of this high speed sprinting, aerodynamic skull, large heart muscles – all these things associated with the high speed the cheetah demonstrates.”

The University of Edinburgh’s Ross Barnett, who did not take part in the study, called the research “pretty solid” and said that it serves to confirm what many already believed about the cheetah.

“What’s interesting to me is that they seem to pick up and confirm the hypothesis that was developed in earlier studies: that cheetahs are extremely lacking in diversity. It has long been known that cheetahs had many unusual features that suggested they lacked diversity but this genome data seems to confirm it for sub-saharan African cheetah,” he said by email. “What I would have liked to have seen would have been comparison to the severely endangered Persian cheetah (Acinonyx jubatus venaticus). Other studies of limited mtDNA and neutral micro satellite data that include Asiatic cheetah suggest that the lack of diversity in cheetah might be a regional artefact.”

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O’Brien said he hopes their work can not only spell out the evolution of cheetahs but provide data that could help ensure their survival.  Deemed vulnerable by the International Union for Conservation of Nature and Natural Resources, there are less than 10,000 in the wild with almost all of them in South Africa and Eastern Africa.

The cheetah numbers are declining - they have fallen 90 percent in the past 100 years - mostly due to a loss of habitat, illegal trade of the live animals and death from illegal hunters, angry farmers as well as motorists hitting  them on highways.

“Sequencing the cheetah genome illuminates our understanding of the species’ evolutionary past and aids us in efforts to sustain and increase cheetah populations in their present and former range,"  Laurie Marker, the founder and executive director of the CCF and a co-author on the study, said by email.

"By understanding the history of the species' migration, its
population bottlenecks and lack of genetic diversity, scientists and conservationists can work together to develop informed strategies to protect the species,” she said. “Although human
intervention has caused many problems for the cheetah, humans also have the ability to change the cheetah’s future."

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And as researchers consider measures to save the cheetah, O’Brien and others said the genome - as flawed as it is - offers plenty of hope these speedy cats.

“Yes, the cheetah does show the correlates of inbreeding expressed in reproduction, expressed in immune response genes. However, those traits - as recognizable as they are - have not been rate limiting on the cheetah’s expansion,” O’Brien said.

“The cheetah’s last bottleneck was 10,000 years ago so that means we have had 2,000 generations where the cheetahs have risen up to hundreds of thousands. That means they are able to breed, overcome these problems,” he continued. “They are able to have offspring even though their sperm is bad, even though some of them are infertile. All of these problems that we are seeing are not a death sentence but actually the cheetah is a success story for overcoming it.”