Thoughts on T.S. Eliot, Ernest Hemingway and genetics

Cats are cool. Everybody knows that. Cats can also have very characteristic traits. Everybody knows this, too, particularly since Andrew Lloyd Webber’s musical Cats, where he popularised T.S.Eliot’s collection of poems Old Possum’s Book of Practical Cats. Remember them? Gus, the theatre cat? “His coat’s very shabby/ He’s thin as a rake/ And he suffers from palsy that makes his paw shake”. The Old Gumbie Cat? “Her name is Jennyanydots/ Her coat is of the tabby kind with tiger stripes and leopard spots”. And the list goes on.

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“Macavity. Macavity, there’s no one like Macavity. / He’s a fiend in feline shape. / A monster of depravity.”

Yet, not only lovers of literature and music are enthralled by the diversity of features that cats display. Geneticists have also long discovered this phenomenon, which can be very useful to figure the genetic changes that are responsible for a given trait (geneticists call these traits “phenotypes”). So, ok, obviously noone has ever found the Mr. Mistofelees-mutation or the Rum-Tum-Tugger allele, but some of the other things they’ve been looking into is still pretty amazing.

One of my favorite studies (Lettice 2008) looks into the genetics of polydactyly (having more than the normal number of fingers) in cats. Polydactyl cats often look pretty funky, because it appears as if they were wearing mittens thanks to the additional fingers. These cats are also named Hemingway cats, after Ernest Hemingway, who wasn’t only a writer, but also a cat-lover. He was given a six-toed cat from a ship’s captain, and “one cat leads to another”, as Dave Gonzalez, the public affairs director of the Ernest Hemingway Home and Museum in Key West, put it.

A large colony of 40-50 cats, many of them polydactyl and descendants from the original founder cat, can still be seen at the Hemingway museum. But polydactyly is not unique to this colony, and can also be found elsewhere. The study I mentioned, appeared a couple of years ago, and looked specifically at an enhancer (an “on”-switch) of a gene called Sonic hedgehog, which is often altered in humans with polydactyly. They found that polydactyl cats from the Hemingway colony and the UK also have alterations of this enhancer, and this is probably causal for the phenotype. In the cats from the Hemingway colony they also saw that all animals with polydactyly had the same mutation, which is what you expect, since the trait got passed on from a single ancestor.

But cat coolness is not only paw-deep. This month another study was published (Buckingham 2013), this time investigating the cause for taillessness in cats.

The Manx cat has become a national symbol of the Isle of Man, and is even featured on their coins.

The Manx cat has become a national symbol of the Isle of Man, and is even featured on their coins.

There are multiple different cat breeds with this phenotype, including one called Manx. Today’s Manx cats originate from the Isle of Man, and one of their characteristic traits is a tailless phenotype of varying degree, from no tail (rumpy), through small tail (stumpy) to almost full-length tails (longy). This trait is dominant (ie to be tailless, it is sufficient for animals to inherit the mutation from only one parent, but not from the other), but the phenotype has variable expressivity (not every cat with the mutation will have the same extent of taillessness) (Robinson 1993).

In this recent study, the authors investigated a gene called “T”, which has already been associated with tailless phenotypes in mice and dogs. In their study, they identified multiple mutations, which would all result in loss-of-function of the T gene, and none of which were found in cats with normal tails from the same pedigree. The authors therefore argue that the identified variants are likely the causal ones for the tailless phenotype. Unfortunately, interpretation of their data is not that simple: remember how all of the cats at the Hemingway colony shared the same mutation because they shared the same ancestor? Well, you sort of would expect the same for the Manx cats, because the cat population on the Isle of Man is probably pretty small, so it is likely that tailless cats from the island also share an ancestor (this is called a “founder effect” in genetics). But this is not what the authors found: they found multiple different variants in different Manx cats, which is rather surprising. Of course the genome of a cat is a big place, so it is possible there is a single, shared mutation somewhere, where the researchers didn’t look. One likely place could be the beginning of the T gene, which the authors were not able to test. Alternatively, it could be somewhere completely different. In dogs, for example, most, but not all, bob-tailed breeds have alterations in the T gene (Hytönen 2009). Definitely, some more more analysis will be needed.

Nevertheless, I hope I could convince you that cats are pretty great animals for geneticists to study. As I mentioned, some of their special traits, such as polydactyly or taillessness, can also be observed in other mammals (eg dogs, mice, even humans). Therefore, by understanding and comparing the genetic causes of these traits in multiple species, we can obtain a more general view of how the genetic code shapes our bodies, and how this has evolved. Amazing, where a little TS Eliot can get you…

——

References:

Lettice LA, Hill AE, Devenney PS, Hill RE. (2008) Point mutations in a distant sonic hedgehog cis-regulator generate a variable regulatory output responsible for preaxial polydactyly. Hum Mol Genet 17 (7):978-85

Robinson, R. (1993) Expressivity of the Manx Gene in Cats. J Hered 84 (3): 170–2.

Buckingham KJ, McMillin MJ, Brassil MM, Shively KM, Magnaye KM, Cortes A, Weinmann AS, Lyons LA, Bamshad MJ. (2013) Multiple mutant T alleles cause haploinsufficiency of Brachyury and short tails in Manx cats. Mamm Genome, Epub ahead of print

Hytönen MK, Grall A, Hédan B, Dréano S, Seguin SJ, Delattre D, Thomas A, Galibert F, Paulin L, Lohi H, Sainio K, André C (2009) Ancestral T-box mutation is present in many, but not all, short-tailed dog breeds. J Hered 100 (2):236-40

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2 thoughts on “Thoughts on T.S. Eliot, Ernest Hemingway and genetics

  1. Thank you for noting what excellent science cats help make. As far back as Schrodinger’s cat, Quantum, cats have been proving their scientific stuff. Cats and science go together like band-aids and bleeding. We must remember to respect our little lab partners though.

  2. Pingback: Cats vs. Dogs: A poem by T. S. Eliot | DIANABUJA'S BLOG: Africa, the Middle East, Agriculture, History & Culture

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