Relaxed Selection During a Recent Human Expansion

Genetics: A Periodical Record of Investigations Bearing on Heredity and Variation

Vanessa Bruat^6¹  Stephan Peischl^1,2,3²  Alexandre Gouy^1,2³  K. J. Gilbert^1,2⁴  Jean-Christophe Grenier^6⁵  Adrien Foucal^1,2⁶  Isabelle Dupanloup^1,2,4⁷  Michèle Jomphe^5⁸ 

[1]Balsac Project, University of Quebec at Chicoutimi, Saguenay, Quebec, G7H 2B1 Canada^5

[2]Computational and Molecular Population Genetics Laboratory, Institute of Ecology and Evolution, University of Berne, 3012, Switzerland^1

[3]Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King’s College London SE1 9RT, United Kingdom^7

[4]Department of Molecular Genetics, Ontario Institute for Cancer Research, University of Toronto, Ontario M5G 0A3, Canada^8

[5]Hôpital Ste-Justine, University of Montréal, Quebec H3T1C5, Canada^6

[6]Interfaculty Bioinformatics Unit, University of Berne, 3012, Switzerland^3

[7]Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland^2

[8]Swiss Integrative Center for Human Health SA, 1700 Fribourg, Switzerland^4

关键词: range expansion;    Quebec;    mutation load;    genetic drift;   

DOI  :  10.1534/genetics.117.300551

学科分类：医学（综合）

来源: Genetics Society of America

【 摘 要 】

Humans have colonized the planet through a series of range expansions, which deeply impacted genetic diversity in newly settled areas and potentially increased the frequency of deleterious mutations on expanding wave fronts. To test this prediction, we studied the genomic diversity of French Canadians who colonized Quebec in the 17th century. We used historical information and records from ∼4000 ascending genealogies to select individuals whose ancestors lived mostly on the colonizing wave front and individuals whose ancestors remained in the core of the settlement. Comparison of exomic diversity reveals that: (i) both new and low-frequency variants are significantly more deleterious in front than in core individuals, (ii) equally deleterious mutations are at higher frequencies in front individuals, and (iii) front individuals are two times more likely to be homozygous for rare very deleterious mutations present in Europeans. These differences have emerged in the past six to nine generations and cannot be explained by differential inbreeding, but are consistent with relaxed selection mainly due to higher rates of genetic drift on the wave front. Demographic inference and modeling of the evolution of rare variants suggest lower effective size on the front, and lead to an estimation of selection coefficients that increase with conservation scores. Even though range expansions have had a relatively limited impact on the overall fitness of French Canadians, they could explain the higher prevalence of recessive genetic diseases in recently settled regions of Quebec.

【 授权许可】

CC BY