Using a unique combination of genomic and historical data, researchers from SIB at the University of Bern, in collaboration with the University of Quebec at Chicoutimi (UQAC), the University of Montreal and the University of Toronto, have shown that individuals whose ancestors were at the front of the Quebec colonizing wave exhibit genetic difference compared with those whose ancestors remained in the core of the settlement, which cannot be explained by consanguinity. The findings, published in Genetics, have broad implications for disease incidence in expanding human populations.

An increased risk of genetic diseases in recently colonized areas

The population of Quebec shows a higher risk of genetic diseases in some recently settled areas, for reasons that are still hotly debated. Thanks to the province's extremely well documented European settlement history, scientists were able to unravel new factors involved in this risk.

By combining extensive genealogical (BALSAC database) and genomic information (CARTaGENE) about individuals who descended from the initial wave of European colonization of Quebec, SIB scientists Stephan Peischl and Isabelle Dupanloup Duperret, University of Bern, found clear evidence that individuals whose ancestors were mainly situated at the pioneering front of the wave had accumulated mutations at a higher rate than those whose ancestors stayed mainly in core areas that had already been colonized.

"Our results might explain the higher prevalence of some genetic diseases in Quebec," says SIB Group Leader Laurent Excoffier. He continues: "This excess of harmful mutations has sometimes been attributed to consanguinity in isolated populations. Our study shows that this interpretation is not justified."

The genetic burden of pioneers: an explanation

The accumulation of harmful mutations that was observed in individuals descending from pioneer ancestors can be explained thanks to the recent theoretical work conducted in Excoffier's team at the University of Bern. Building on computer simulations, experimental evolution and human DNA datasets, the team had previously showed that natural selection is not very effective at purging harmful mutations on colonization fronts, as these regions are usually less densely populated than core areas.
This is the first time, however, that the phenomenon has been demonstrated in such a young population as that of Quebec. "The fact that we can see any meaningful differences between the two groups of individuals is quite stunning, as they must have emerged only since their recent geographical divergence, about six to nine generations ago - a very short time on the evolutionary scale," says Peischl.
"Our findings of a mutation load showing up after so few generations could provide the cues to explaining current patterns of disease incidence in other modern humans, which underwent periods of range expansions for hundreds of generations in some instances," Excoffier concludes. "Testing such hypotheses requires ancient DNA from pioneer populations to become available."

S. Peischl et al. Relaxed selection during a recent human expansion. Genetics, February 1, 2018 vol. 208 no. 2 763-777;

Read the full press release from UQAC in English or in French

More on the topic - Harmful mutations and range expansion: computers got it right

Read Laurent Excoffier's interview in Le Temps (10 May 2018)

Monts ValinView of the Monts Valin and Saguenay River, Quebec. Credit: Reo Blackburn