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Genomic Evidence for the Unique Physiology
of
African Cheetahs

Image courtesy of naturalwolrdsafaris.


1) What was the research project?

The 2015 study, Genomic legacy of the African cheetah, Acinonyx jubatus, published in Genome Biology discusses how the species’ genomic history can provide insight into how cheetah’s evolved into the world’s fastest land animal (Dobrynin, et al., 2015); and how their lack of genetic diversity has led to their near extinction status.

2) Were they testing a hypothesis or doing discovery science?

This project was discovery science, because it was already documented prior to the project that there was a “genome-wide reduction of cheetah diversity and gene adaptations that occurred in the cheetah’s evolutionary lineage” (Dobrynin, et al., 2015). The group's goal was simply to acquire and analyze the whole-genome sequence of the African cheetah in order to affirm information known about the genetic history of the species.

3) What genomic technology was used in the project?

The sequencing of the Acinonyx jubatus genome from the samples of seven cheetahs was done on the Illumina HiSeq2000 platform using a shotgun-sequencing approach. The variable nucleotide sites were identified and compared to single nucleotide variations (SNV) in mammals and other Felidae species.   


Fig. 1a.
Estimates of genome diversity in the cheetah genome relative to other mammal genomes. a) SNV rate in mammals. SNV rate for each individual was estimated using all variant positions, with repetitive regions not filtered. (replicated Dobrynin, et al., 2015).

Fig. 1c.
Estimates of genome diversity in the cheetah genome relative to other mammal genomes. c) Number of SNVs in protein-coding genes in felid genomes. (replicated Dobrynin, et al., 2015).

The group used snpEff to identify SNVs showing possible deleterious effects. (Dobrynin, et al., 2015).

4) What was the take home message?

The study found that overall, cheetahs displayed a far more accelerated accumulation of non-synonymous mutations relative to other species (Dobrynin, et al., 2015).

Fig. 4. Comparison of Dn/Ds distributions for reproduction-related and all cheetah genes. [The Dn/Ds ratio is a fundamental measure of the relative importance of selection and genetic drift in causing amino-acid substitutions.] a) Distributions of branch-specific values of Dn/Ds for reproductive system genes. Dn/Ds ratios were calculated for five species (dog, human, cat, tiger and cheetah) based on 500 bootstrap replications and the free-ratio model in PAML [37]. b) Distributions of branch-specific Dn/Ds values for four species (dog, cat, tiger and cheetah) and ancestral reconstructed Felidae branch. Dn/Ds ratios for branches based on 200 bootstrap replications of 10 Mb protein-coding sequences. (replicated Dobrynin, et al., 2015).

The study reveals that on the genome of wild-born African cheetahs on average are 95% homozygous, which is extremely high. This information is reflected in the cheetah’s genomic sequence, where there is a drastically high genomic depletion of SNV incidence, SNV density, SNVs of coding genes, MHC class I and II genes, and mitochondrial DNA SNVs (Dobrynin, et al., 2015).

The study also concludes that the lack of genomic sequence diversity in modern cheetahs was caused by two bottleneck events (the first occurring about 100,000 years ago and the second occurring about 12,000 years ago.

5) What is your evaluation of the project?

The modern cheetah and its title as the fastest land animal has always fascinated humans. Scientists in particular want to provide the reason why cheetahs have been able to evolve into a 60 miles per hour predator. By learning more about the genetic patterns and history of African cheetahs, humans might become better equipped to protect this endangered species and increase cheetah population numbers.

My main issue with this paper was that the group seemed too caught up in trying to “force” the data to prove the information about cheetahs that was discussed in the background section of the article.

As a scientist, there should always be a red flag when there are great summaries about the research but the data itself is difficult to understand. I found that, out of the 5 figures shown in the project, only two of them were very clear to understand.

In the original article, Figure 2 was supposed to compare the MHC region structure between cheetahs and domestic cats. The data is not clear to the reader but is supposed to support why unrelated cheetahs did not adhere to the normal rate of tissue rejection. Instead the unrelated cheetahs tolerated skin grafts, similar to that of identical twins. I could not conclude from the figure how cheetahs expressed a loss and reduction of function in the MHC class I gene.

In the original article, Figure 3 seemed more difficult to understand than Figure 2, and the color spectrum was hard to reference even if the reader did understand the data model. The reader was supposed to understand that the DaDi software tool could be used to predict the most likely evolutionary scenarios from the allele frequencies of two cheetah populations (southern Namibia and eastern Tanzania).

 

References

Pavel Dobrynin†, Shiping Liu†, Gaik Tamazian, Zijun Xiong, Andrey A. Yurchenko, Ksenia Krasheninnikova, Sergey Kliver, Anne Schmidt-Küntzel, Klaus-Peter Koepfli, Warren Johnson, Lukas F.K. Kuderna, Raquel García-Pérez, Marc de Manuel, Ricardo Godinez, Aleksey Komissarov, Alexey Makunin, Vladimir Brukhin, Weilin Qiu, Long Zhou, Fang Li, Jian Yi, Carlos Driscoll, Agostinho Antunes, Taras K. Oleksyk, Eduardo Eizirik, Polina Perelman, Melody Roelke, David Wildt, Mark Diekhans, Tomas Marques-Bonet, Laurie Marker, Jong Bhak, Jun Wang, Guojie Zhang and Stephen J. O’Brien. 2015. Genomic legacy of the African cheetah, Acinonyx jubatus. Genome Biology. 16:277.
†Contributed equally. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676127/pdf/13059_2015_Article_837.pdf

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