Thursday, June 13, 2013

My dogs' evolutionary history. Part 2: Results

Yesterday we made the predictions of the breed signatures we'd find in our dogs' DNA.

If you didn't already, please consider going back to yesterday's post first before reading today's. Predictions are key! It's best if you confirm our guesses and/or add your own. (...what are the reasons for your predictions? Size? Color? Ears? Tails? Fur? Snout? Furnishings?)

Sadly (yes, sadly), predictions are not part of the official Wisdom Panel or 23andMe experiences. When I teach with 23andMe predicting the results is a major assignment early in the semester. Not only is making predictions the best practice for later scientific evaluation of the results, and it's the best way to force yourself to come to terms with how inheritance and gene expression work (and don't work), but guessing the outcome first makes reading the results orders of magnitude more fun ... not to mention how it makes things a lot less nerve-wracking when it's about your own DNA with 23andMe.

Briefly, before I reveal our dogs' results, let's consider a couple important things first...

Dog breed markers are mutations. 
Just like anything else alive right now, all dog breeds, no matter how "pure" or revered, are mutants. All of their dog traits just like all of our human traits, good and bad, started out as new mutations. Even the ones we all share that contain little variation now (like our genes involved in the development of five fingers and five toes), but also the ones that vary among our populations (like our genes that affect our pigmentation).

And mutations aren't just a population thing; each of us has a tiny fraction of our genome that's mutated compared to our parents. As far as we know, mutations occur in the making of all babies and puppies, etc. Most are neutral, some are bad, some are good.

We're all mutants because mutation, perpetual change generation upon generation within a lineage, is constant. Stasis is not.

This constant change in every puppy is fundamental to why we can have hundreds of dog breeds today.

Many dog breed traits are genetically simple.
Dogs seem to be particularly simple kinds of mutants.

The mutated genes that determine the traits that distinguish one dog breed from another are remarkably few and remarkably simple, but that simplicity makes a lot of sense.

Since humans coaxed these breeds out of ancestral dog stocks and also out of other breeds (as they still do today), it's easy to imagine that new simple traits, not new complex ones, had the best potential to be easily and quickly propagated into future generations and eventually into new breeds.

If a trait arose that was preferred, and it was caused by the kind of genetic mutation that could be simply and somewhat reliably expressed in offspring that inherited it, that mutation and the trait it produced could be increased in future generations by promoting breeding of those new attractive mutant dogs and their offspring.
If dog breed traits were genetically complex (based on many genes, for example), they would be terribly difficult to produce through controlled breeding of parents with those traits... at all... let alone during one human breeder's lifetime! That's at least partly because there would be far too many puppies without the preferred trait and it would be far too difficult to preserve a trait at an appreciable frequency in a lineage. Of course, inbreeding with very close relatives that share the mutations helps a great deal with this.

Humans have taken advantage of the simple mutations that have popped up in dogs (as they pop up in all living things!), due to sheer feasibility of the breeding outcomes those simple mutations allowed. Like that new coat curl or those new furnishings? Some puppies will have the exact same look. And we're off and running with a new kind of dog...
I don't know about the genes for Dalmatian spots (and honestly haven't even looked) but I do know about this paper by Cadieu and colleagues from 2009. Apparently you need only three genes (FGF5, RSPO2 and KRT71), each with two alleles (i.e. gene variants; denoted +/- in the figure below) to explain all this coat variation among dogs:

Cadieu et al., 2009
Dog genes are made of the same goop that ours are, and their genomes are very similar to ours because of our shared mammalian ancestry, but they're described as "simple." Evan Ratliff explains some more about why dog genes are simple in "How to Build a Dog:"
The vast mosaic of dog shapes, colors, and sizes is decided largely by changes in a mere handful of gene regions. The difference between the dachshund's diminutive body and the Rottweiler's massive one hangs on the sequence of a single gene. The disparity between the dachshund's stumpy legs—known officially as disproportionate dwarfism, or chondrodysplasia—and a greyhound's sleek ones is determined by another one. The same holds true across every breed and almost every physical trait. In a project called CanMap, a collaboration among Cornell University, UCLA, and the National Institutes of Health, researchers gathered DNA from more than 900 dogs representing 80 breeds, as well as from wild canids such as gray wolves and coyotes. They found that body size, hair length, fur type, nose shape, ear positioning, coat color, and the other traits that together define a breed's appearance are controlled by somewhere in the neighborhood of 50 genetic switches. The difference between floppy and erect ears is determined by a single gene region in canine chromosome 10, or CFA10. The wrinkled skin of a Chinese shar-pei traces to another region, called HAS2. The patch of ridged fur on Rhodesian ridgebacks? That's from a change in CFA18. Flip a few switches, and your dachshund becomes a Doberman, at least in appearance. Flip again, and your Doberman is a Dalmatian. "The story that is emerging," says Robert Wayne, a biologist at UCLA, "is that the diversity in domestic dogs derives from a small genetic tool kit."
So it's this simplicity that allows companies like Wisdom Panel to genetically distinguish breeds and then look for the signatures/markers of those breeds in our dogs' DNA. It's also the recency of most of these breeds (no more than a few to several hundred years at most) that allows us to assume (maybe not rightly but still...) that so much of what genetically identifies a breed today is similar to what the breed was working with all along.

And so... without further ado...

Here are the results of mailing off our dogs' cheek swabs and having 321 markers for 200 breeds analyzed.

For Elroy...
This is his "Breed Ancestry Certificate"

The report notes how Rottweiler and Chow Chow are the only ones with confidence. 

How do they make the pedigree chart? 
What I think they do is estimate what percent of the breed contributes to the dog's ancestry and if it's something like 50%, it's one parent. If it's like 25%, it's one grand-parent and if it's like 12.5%, it's one great-grandparent. Any % less than that is lumped into "mixed breed" ... the details of those are guessed at below.  So those placements on either side of his chart are just best fit in terms of percentage. 

What I'm not sure about is why we must assume that 100% of Elroy's ancestry comes from any breed. But, remember that 100% of the markers in the Wisdom Panel test distinguish breeds. That means, this Breed Ancestry Certificate is missing all the information about Elroy that's not analyzed by Wisdom Panel. 

We guessed the breeds that they were confident about! There must be something to this test. Especially since we had seen his litter mates and were told by the adoption agency that he was probably rott/sharpei (and later on we figured he was just as likely chow chow as sharpei). SCIENCE works.

German Shepherd and Collie aren't terribly surprising either. He came from Ohio. Those breeds are abundant enough in the region, are allowed to roam free and probably mated like that too for decades upon decades in those regions. And he's a big boy!

But Westie? Westie is a bit of a head-cocker.

Or is it? Westies had to have had big ancestors, first of all, since they descended from wolf ancestors like all other dogs. But something that distinguishes Westies from other breeds is in Elroy's DNA. That means a relatively recent Westie left a signature in his genome. So was it kamasutra lovemaking between tiny Elroy ancestor and big Elroy ancestor?  Or are we talking about love between mixed breeds and pure breeds and mixed breeds over time? Probably.

Here are their best guesses about what contributed to those "mixed breed" mysteries on his certificate.
Mostly big dogs, some ancient and awesome. The Dogo! (Ugh, don't google it... so many fighting and abuse videos.)

Nothing to really take home from this list because they're far off guesses without even a report of percentage there with the bar graph.

For Murphy...
This is her "breed ancestry certificate"

Akita, German Shepherd and Lab are the only confident ones (as noted in the report). 
And here are the most likely breeds contributing to those "mixed breed" mysteries on her certificate.

Shepherd! And Lab is another good one considering friends and relatives see lab in her.
Many of her mix guesses are herders!

Akita? That's phenotypically (and maybe genetically(?) will have to check) close to Husky which is another guess we often hear for her. So this is only a little bit surprising.

French Bulldog? Now that's a real head-cocker.

But again, like with the Westie, it's not noted as "confident" in the report, but on the other hand, why not French Bulldog in her ancestry? It just means this is a marker, like with the Westie, that's not tied to outward appearance/phenotype.*

Not enough information...
I wonder what these markers are then; if Westie and French Bulldog are showing up, why? As the website explains, “Physical features characteristic of certain breeds, such as the flattened face of the English Bulldog or the extremely curled tail of the Pug, seldom survive even the first crossbreeding.”

So these markers for unseen traits are fascinating but not explained in the report.  I'm spoiled rotten by 23andMe that tells you everything, down to the A,T,C, or G you have for your allele for whatever gene. I'm guessing that Wisdom Panel keeps all this under wraps because (a) most consumers don't care to know those details and (b) it's in their best competitive and economic interests to keep their methods to themselves.

What's interesting is how some of the hype about these dog tests is similar to 23andMe: They're "for your health!" But unlike with 23andMe, Wisdom Panel says that you're good just going to your vet and saying "she's got Akita in her blood" when you're dealing with health issues.  While 23andMe advocates that you know each and every SNP.  My health is more important than my dog's I suppose, but what's absolutely not clear is how these two very different approaches (ancestry and family history vs. SNP data) are resulting in different health outcomes.

As you might imagine, there's a lot more to say about the evolutionary and anthropological issues these dog tests raise, so please stay tuned. (Here's part 3.)

Kevin and me and our Westie, Elroy, and our French Bulldog, Murphy.

*Or if it is, it's present in only one recessive copy and would require two copies for the visible trait in the Westie or French Bulldog  to be expressed (added June 14)

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