Population data from Quebec reveals the genetic consequences of rapid human expansions.
The majority of the 6.5 million French Canadians living in Quebec today can trace their heritage to just 8500 settlers who formed clusters around the Saint Lawrence River in the early 17th century. Most remained near those riverside settlements until 200 years later, when some began colonizing more remote regions. Despite their shared heritage, the descendants of those who stayed near the river and those who moved on are already genetically divergent, and for unknown reasons, those living in more recently colonized areas of Quebec have a higher prevalence of recessive genetic disorders.
To understand the relationship between the settlers’ movements and their genetic differences, researchers sequenced the genomes of selected people living near the frontiers and others in the core near the river. They found that, on average, frontier individuals have lower levels of genetic diversity, but their genetic variants are more detrimental than those found in the people in the core are. This pattern is even stronger for mutations that are rare—and, thus, likely more harmful—and the frequency of these rare mutations decreases with their harmfulness in the core population but not in the frontier population.
There are many possible explanations for this—inbreeding, for example—and the researchers needed to take more information into account to determine the true cause. This information came from their own study subjects: the team had specifically chosen the subjects because they could confidently trace the subjects’ ancestry using historical records and detailed genealogical information. Delving into this information revealed that inbreeding was only marginally more common at the frontiers and was nowhere near prevalent enough to account for the genetic differences they observed, allowing them to rule it out as a possible cause.
Combining all three sources of information—historical, genealogical, and genomic data—revealed that the observed harmful genetic variants infiltrated the frontier population via increased genetic drift and relaxed selection. The researchers suggest that this is due to higher fertility and reduced competition at the frontiers, which allowed people living there to transmit their genes irrespective of their intrinsic fitness.
That such a difference between the two groups could manifest in just six to nine generations is remarkable. Although the effect on fitness in most individuals is likely small, the differences could help explain the increased prevalence of recessive genetic disorders in recently settled areas of Quebec. Over a greater number of generations, the effects of relaxed selection would be expected to be more pronounced, so if the same principle applies to the many other waves of human expansions that characterize our genetic history, it may have helped shape how genetic disease burden varies around the world.
Relaxed Selection During a Recent Human Expansion
Stephan Peischl, Isabelle Dupanloup, Adrien Foucal, Michèle Jomphe, Vanessa Bruat, Jean-Christophe Grenier, Alexandre Gouy, K. J. Gilbert, Elias Gbeha, Lars Bosshard, Elodie Hip-Ki, Mawussé Agbessi, Alan Hodgkinson, Hélène Vézina, Philip Awadalla, Laurent Excoffier
Genetics 2018 208: 763–777; https://doi.org/10.1534/genetics.117.300551