What makes your bulldog look different?

Darwin in the first chapter of his treatise “On the Origin of Species By Means of Natural Selection” talks about variation in domestic animals. He starts the chapter by saying:

“When we look to the individuals of the same variety or sub-variety of our [….] animals, one of the first points which strikes us, is, that they generally differ much more from each other, than do the individuals of any one species [….] in a state of nature.”

Read it once more, YES!!! he said that there is more variation (breeds or varieties) among domesticated “species” like dog, cat, coconut palms etc., when compared to wild animals (or plants) like Lion (which has no breeds or varieties). He says (recognizes) that it is due to selective breeding. But how did this variety occur? He provide clues a few sentences later in the same chapter.

“But I am strongly inclined to suspect that the most frequent cause of variability may be attributed to the male and female reproductive elements having been affected prior to the act of conception.”

Remember that no one knew about genes, and alleles as the basis of heridity at Darwin’s time. So his was a new observation, that guided us later. So is there any one out there fascinated about the variety among domestic animals those reproductive elements? You have a really great paper to read which shows the mechanism of evolution, the process of fixation of a variation and passing over of that variation by Schoenebeck and others. These kind of studies, does, not only study how a breed evolved but also shows us the greater picture of how evolution occurs. In a meticulously worked out paper, which should be a hard read for non-experts, they study dog breed skull shape variations.

The paper starts saying that “dog breed skull shape diversity is a largely human created phenomenon (paraphrased)”, through artificial selective breeding.

What does the paper say about this skull shape variation? It says many things but importantly provide fascinating details about how a single mutation could lead to a prominent change in skull shapes. There are more details and it is not just about a mutation, although.

They looked at two extremes of skull shapes one with flat snouts and the second with long snouts. In essence they analyze, dog skull shapes, by grouping the Bulldogs, Boxers, Pitbulls, Pugs etc., in one extreme and the Collies, Greyhounds, Saluki etc., in the other extreme. Other breeds fell in between these extremes, for the skull shapes, of long snout (dolichocephaly) to flat snout (brachycephaly).

In a very rigorous analysis they found that the change in an amino acid (building blocks of proteins) on the 452nd position of the bone morphogenetic protein 3 (BMP3) gene of brachycephalic dogs have been the reason of their short snouts. It is easily said in a sentence, but the authors have put in a lot of details, they even show the a similar mutation when induced in the zebrafish, can make its cranio-facial morphology to go weird—similar to your pitbulls!!

Brachycephalic dogs have an amino acid named Leucine (L) at the 452nd position of the BMP3 gene, which is normally an amino acid called phynylalanine (F) in normal snouted dogs and other animals. So was it a “abracadabra” F452L that produced brachycephalic dogs? Yes and no, this mutation somehow formed in few dogs, which (dog) was seen by multiple independent breeders to develop such diverse brachycephalic breeds. Now these researchers see and present us the mutation as a story about what happened while selectively breeding such variants.

If you are not a science student, you should be exhausted by now, ok that is it remember F452L!!!! And remember next time when you play with your bulldog ask it about that Leucine!!!

For interested people read further or grab the freely download-able paper at the PloS Genetics Website.

They started analysing skull shapes of dogs, available in museums and private collections. The “shifts” in shape was examined by measuring more than 500 skulls from more than 100 different breeds of dogs. The 3D measurements were statistically analysed to explain the variation among the measurements between each breeds, and they found a sub-set of “promising” measurements that could explain the changes in skull shapes.

In the next step they used this “phenotype” data to do an association study, for the genotype data they generated. The paper explicitly says that the task was straightforward since pure-bred dogs would have a very strong visual phenotype, that would not vary, thus could be used to correlate the genotype data when generated from similar pure-bred animals. So they carried out genome-wide scans to detect any genotype association to a breed phenotype, using SNP datasets.

They found 5 promising Quantitative Trait Locii (QTL’s), for which there was strong association with the “flat snout-long snout” phenotype range. One of these QTL’s contained regions of genes BMP3 and PRKG2. They could zero down on the BMP3 gene or the bone morphogenetic protein 3 gene position 452. This position possess an amino acid called Leucine, in flat-snouted dogs, instead of another amino acid called phenylalanine which is found in normal snouted breeds.

NB: I would not mind, as a reader, if they had made the abstract and the introduction a bit longer 🙂

Jeffrey J. Schoenebeck, Sarah A. Hutchinson, Alexandra Byers1, Holly C. Beale, Blake Carrington, Daniel L. Faden, Maud Rimbault, Brennan Decker, Jeffrey M. Kidd, Raman Sood, Adam R. Boyko, John W. Fondon III, Robert K. Wayne, Carlos D. Bustamante, Brian C (2012). Variation of BMP3 Contributes to Dog Breed Skull Diversity PLoS Genetics, 8 (8)