by Greg Mayer and Jerry Coyne
Our felid for today is actually five felids: a mackerel (striped) tabby, a blotched tabby, a spotted cheetah, a king cheetah and a black-footed cat. In a new paper in Science by Christopher Kaelin and colleagues, the physiological basis of these pattern variations in both domestic cats and cheetahs is shown to be due to mutations at the Transmembrane aminopeptidase Q locus (Taqpep for short ) that alter the function of its encoded protein, which they call Tabulin.It has long been known that the dark areas in a tabby’s coat are places where the hairs are colored mostly by eumelanin (a darker pigment), while the hairs of the lighter areas have more phaeomelanin (a lighter pigment). In both areas, the individual hairs have bands of color (look closely at your cat’s hairs: you’ll see that few are unicolored– most are banded in some way). In mackerel tabbies, the dark and light areas are arranged in a periodic pattern, creating tiger-like stripes. This is the pattern found in the wild cats that are the domestic cat’s progenitors, and is still one of, if not the, most common patterns in domestic cats.
It has also long been known that the blotched tabby condition is due to recessive alleles at an autosomal (i.e., non sex-chromosomal) locus, called Ta, so that having two copies of the mutant allele b makes the tabby blotched. What Kaelin and colleagues have done is show that the Ta locus is in fact the gene Taqpep. In domestic cats, blotched tabbies have one (or more) of three single nucleotide mutations that alter the Tabulin protein’s function. If you have one copy of the dominant (M) allele, you’re mackerel (see diagram above).
One of the coauthors of the paper is Ann van Dyk, who, back in 1986, with R.J. van Aarde, first definitively demonstrated that king cheetahs, at one time thought to be a different species and the object of much cryptozoological speculation, were in fact a color-pattern variant of the common cheetah, with the same mode of inheritance as the blotched tabby: an autosomal recessive gene.
In the new paper Kaelin et al. extend their work to cheetahs, sequencing their Taqpep genes, and found that in king cheetahs there is a single base pair insertion in the gene that causes a frameshift, a type of mutation that alters every amino acid encoded downstream in the gene from the site of the insertion. Thus the king and blotched patterns result from alterations of a homologous gene, but the mutations themselves are not identical, being caused by a single nucleotide substitution in domestic cats but by an insertion in cheetahs.
Kaelin et al. also sequenced the Taqpep locus in 29 other species of wild cats, assessing any nonsynonymous substitution (i.e., those that change the amino-acid sequence of the protein produced by the gene) for how likely they were to alter protein function. All the cats had “normal” genes, except for the black-footed cat (Felis nigripes), which had five substitutions that were collectively judged as being very likely to alter the protein’s function. Interestingly, the black-footed cat has a pattern similar to domestic cats with a “swirled” pattern associated with the mutation T139N of the Taqpep locus:
Kaelin et al. note that blotched tabbies rarely appear in early illustrations of cats, but that by the 18th century they had become more common. They also note that there is a fairly large region (244kb of nucleotides) around the Taqpep locus that is invariant in blotched tabbies, while it has usual levels of variability in mackerel tabbies. This is the exact pattern, both historically and genetically, that we would expect if the blotched pattern had been favored by (presumably artificial) selection over the last few hundred years.
When an allele is favored by selection, closely linked forms of genes will also increase in frequency (a phenomenon known as “hitchhiking”), leading to higher frequency or fixation for a whole block of genetic material. Recombination will eventually break up the association of the favored and hitchhiking alleles, and new mutations will increase variability; but this dissociatio takes time, and until it happens the region of low variability persists as a record of the selection (which in this case may still be ongoing).
[Note by GCM: While the paper, at five pages, is long by Science's standards, there are still 27 pages of online supplements, and it is difficult to follow the authors' train of argument and evidence since it requires constant switching between the paper and the appendices to fully appreciate what they've done (not to mention it would be impossible to do so if you were reading the journal or a reprint, rather than an online version). More justice would have been done to the authors' work, and to their readers, had a substantially longer paper been published (which, of course, could not have appeared in Science). I mention this not to criticize the authors, but to decry the increasing practice of putting essential parts of a paper into relatively inaccessible and, I fear, ephemeral, appendices.]
Kaelin, C. B., X. Xu, L. Z. Hong, V. A. David, K. A. McGowan, A. Schmidt-Küntzel, M. E. Roelke, J. Pino, J. Pontius, G. M. Cooper, H. Manuel, W. F. Swanson, L. Marker, C. K. Harper, A. van Dyk, B. Yue, J. C. Mullikin, W. C. Warren, E. Eizirik, L. Kos, S. J. O’Brien, G. S. Barsh, and M. Menotti-Raymond. 2012. Specifying and sustaining pigmentation patterns in domestic and wild cats. Science 337:1536-1541. abstract
van Aarde, R.J. and A. van Dyk. 1986. Inheritance of the king coat colour pattern in cheetahs Acinonyx jubatus. Journal of Zoology 209: 573-578. pdf