Dog Evolution Just Got Buggered up

“A comparison of the structures of homologous proteins (i.e., proteins with the same kinds of biological activity or function) from different species is important, therefore, for two reasons. First, the similarities found give a measure of the minimum structure for biological function. Second, the differences found may give us important clues to the rate at which successful mutations have occurred throughout evolutionary time and may also serve as an additional basis for establishing phylogenetic relationships.”Christian B. Anfinsen, The Molecular Basis of Evolution (1959)

Not too long ago I had set up an outline for a blog idea that I had, a “what if” thought-experiment about dog evolution. My notion was to imagine that the dog had naturally diverged from the wolf and had undergone no positive selection by man but evolved by stochastic processes – I was still working on calibration. What would be the “natural” date of divergence?

Like everybody else, I was planning to use mtDNA (mitochondrial DNA) control region because it would allow for more meaningful comparisons to what has already published. Researchers choose mtDNA for practical reasons too; it’s easier to isolate and sequence and the greater rate of change allows you to see patterns more clearly Funnily enough, I was planning to use the brown/polar bear split as an example since that data was readily available and until a few days ago we thought the split happened rather recently. I also thought it was a good choice because like a wolf and dog, the brown and polar bear can successfully hybridize and in many ways the evolution of the polar bear parallels that of the dog. I had set up an alert for the appropriate search terms and that is how I came across this study just published in PNAS.

Miller, W. et al. 2012.  Polar and brown bear genomes reveal ancient admiture and demographic footprints of past climate change. Proc. Nat. Acad. Sci. USA, Published online before print July 23, 2012, doi: 10.1073/pnas.1210506109

The researchers were interested in 3 questions, only the first two are important here. They wanted to know “(i) What is the more precise association between the PB and its sister species, the brown bear; and do we find any signatures of past genetic interchange between the two species? (ii) Did the PB indeed evolve recently, as suggested by mitochondrialDNA and fossil evidence, or did it have an older origin, as demonstrated by nuclear DNA loci? “ The second question is particularly important for those interested in dog evolution since many of the conclusions about dog evolution and breeds is based on mitochondrial DNA instead of nuclear DNA and like in bears the archaeological and genetic evidence conflicts. (Ardalan 2011 Oskarsson 2012, Pang 2009, Pires 2006 )

The black lines represent relationship and divergence based on nDNA and the orange dashed lines on mtDNA. Data based on nDNA gives a 4-5 million year divergence for the PB and BB. The mtDNA also yields some weird and impossible results, making the ABC brown bears more closely related to the PB than the two brown bears (ABC and GRZ) are to each other.

The researchers found major discordance between the dates obtained from mtDNA and nDNA. Based on mtDNA the divergence time for the Brown/Polar bear split established at the relatively recent 150 000 years before present (Lindqvist  2010). Back in April of this year (2012) a report in Science used select fragments of nDNA and pushed back the date to 600 000 years ago. Miller’s work using whole genome analysis pushes the date of divergence to 4-5 million years.

What it means to Dogs

Of course all this talk about bears might change what we think about dog evolution. As I mentioned earlier, mtDNA has been used to create phylogenies, estimate of divergences including the origin of dogs to 16 000 years ago (Pang 2009) and to date the arrival of dingoes into Australia (Oskarsson 2012). Writing about Miller’s findings, evolutionary biologist Dr. Jerry Coyne writes (in CAPS no less):

DO NOT MAKE EVOLUTIONARY TREES OF ANIMALS AND PLANTS BASED ENTIRELY ON MITOCHONDRIAL DNA (mtDNA): PLEASE USE NUCLEAR DNA WHENEVER YOU CAN.  THIS IS BECAUSE mtDNA APPEARS TO MOVE MORE READILY BETWEEN SPECIES THAN DOES NUCLEAR DNA (nDNA), CAUSING A DISCORDANCE BETWEEN EVOLUTIONARY TREES BASED ON MITOCHONDRIAL GENES (‘GENE TREES’) AND THOSE BASED ON POPULATION AND SPECIES HISTORY THAT ARE DISCERNED FROM ANALYSES OF MANY NUCLEAR GENES (‘SPECIES TREES’)

He later notes:

“The problem is that, for reasons we don’t fully understand, mtDNA also moves between species during hybridization much more readily than does nDNA, and that can screw up species relationships.”

Miller et al. write:

“limited evidence from short stretches of mitochondrial DNA suggests that hybridization may have occurred between polar and brown bears shortly after they diverged from one another (8). However, further evidence from biparentally inherited nuclear DNA is required to critically evaluate this possibility, and in particular to determine what fraction of the extant bear genome has been sculpted by gene flow between brown bears and PBs.”

And among the 45 pages of supplementary material was a very important passage.

To learn about bear demographic history and to make inferences about both split times and gene flow, we applied a coalescence hidden Markov model (CoalHMM) to four of our deep-coverage bear genomes: the polar bear (PB7), one ABC brown bear (ABC1), the non-ABC brown bear (GRZ), and the black bear (BLK). We first employed a simple isolation model (36), comparing pairs of genomes under the assumption of allopatric speciation. For all comparisons we obtained unexpected estimates of very recent split times and very large ancestral effective population sizes (Ne). If the true demographics involved were not simple splits but instead initial splits followed by prolonged periods with structured populations and gene flow, these findings would be consistent with misspecification of the demographic model. We therefore applied an extended model, isolation-with-migration, estimating an initial split time followed by a period of gene flow before a complete split.

IOW, when you assume a simple isolation tree model you get recent split times and high effective populations but when you take gene flow between the two newly split branches into account, the divergence time increase but the effective sizes shrink. All these caveats could just as easily apply to dogs and wolves; there are enough parallels to be drawn about polar bear to dog evolution. Like the PB and BB , dogs and wolves likely experienced gene flow (I imagine it was more to wolf ->dog rather than the other way around) and possibly continued for some time as humans took their dogs as they migrated dogs continued to hybridize with new canid populations.

Miller’s study highlights a few problems that should concern those who’ve used mtDNA to draw dog phylogenetic relationships and dates of divergence. Based on what we’ve learned from Miller, we might expect a nuclear DNA analysis to reveal a date older than Savolainen’s 16.5 kya, more admixture and smaller populations. I suspect whole genome analysis may (will?) also reveal older divergence dates. Dog evolution may not be as recent as it is currently portrayed.

Like I said, things have just been buggered up.

REFERENCES Ardalan A, Kluetsch CF, Zhang AB, Erdogan M, Uhlén M, Houshmand M, Tepeli C, Ashtiani SR, Savolainen P.(2011) Comprehensive study of mtDNA among Southwest Asian dogs contradicts independent domestication of wolf, but implies dog–wolf hybridization. Ecology and Evolution. 2011 Nov;1(3):373-85.

Lindqvist, C. et al. 2010.  Complete mitochondrial genome of a Pleistocene jawbone unveils the origin of polar bear. Proc. Nat. Acad. Sci. USA 107:5053-5057 Miller, W. et al. 2012.  Polar and brown bear genomes reveal ancient admiture and demographic footprints of past climate change. Proc. Nat. Acad. Sci. USA, Published online before print July 23, 2012, doi: 10.1073/pnas.1210506109

Oskarsson MC, Klütsch CF, Boonyaprakob U, Wilton A, Tanabe Y, Savolainen P. (2012) Mitochondrial DNA data indicate an introduction through mainland Southeast Asia for Australian dingoes and Polynesian domestic dogs. Proceedings of the Royal Society B 279: 967-974.

Pang JF, Kluetsch C, Zou XJ, Zhang AB, Luo LY, Angleby H, Ardalan A, Ekström C, Sköllermo A, Lundeberg J, Matsumura S, Leitner T, Zhang YP, Savolainen P.  (2009)  mtDNA Data Indicate a Single Origin for Dogs South of Yangtze River, Less Than 16,300 Years Ago, from Numerous Wolves. Mol. Biol. Evol. 26(12):2849–2864. 2009 doi:10.1093/molbev/msp195

Pires A.L. et al. (2006) Mitochondrial DNA sequence variation in Portuguese native dog breeds: diversity and phylogenetic affinities. Journal of Heredity 97: 318-330.

Verginelli F, Capelli C, Coia V, et al (2005) Mitochondrial DNA from Prehistoric Canids Highlights Relationships Between Dogs and South-East European Wolves Mol Biol Evol (December 2005) 22(12): 2541-2551 doi:10.1093/molbev/msi248

Vilà C, Savolainen P, Maldonado JE, Amoim IR, Rice JE, Honeycutt RL, Crandall KA, Lundeberg J, Wayne RK: (1997) Multiple and ancient origins of the domestic dog. Science 1997, 276:1687-1689.

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