Biology subjects

Isabelle Dupanloup

Publications and source records attributed to Isabelle Dupanloup.

4 recordsLinked to original sources

bioRxiv2016

Relaxed selection during a recent human expansion

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 6-9 generations and cannot be explained by differential inbreeding, but are consistent with relaxed selection on the wave front. Modeling the evolution of rare variants allowed us to estimate their associated selection coefficients as well as front and core effective sizes. Even though range expansions had a limited impact on the overall fitness of French Canadians, they could explain the higher prevalence of recessive genetic diseases in recently settled regions. Since we show that modern human populations are experiencing differential strength of purifying selection, similar processes might have happened throughout human history, contributing to a higher mutation load in populations that have undergone spatial expansions.

Genomics↗

bioRxiv2016

Genetic surfing in human populations: from genes to genomes

Genetic surfing describes the spatial spread and increase in frequency of variants that are not lost by genetic drift and serial migrant sampling during a range expansion. Genetic surfing does not modify the total number of derived alleles in a population or in an individual genome, but it leads to a loss of heterozygosity along the expansion axis, implying that derived alleles are more often in homozygous state. Genetic surfing also affects selected variants on the wave front, making them behave almost like neutral variants during the expansion. In agreement with theoretical predictions, human genomic data reveals an increase in recessive mutation load with distance from Africa, an expansion load likely to have developed during the expansion of human populations out of Africa.

Genomics↗

bioRxiv2015

Distance from Sub-Saharan Africa Predicts Mutational Load in Diverse Human Genomes

The Out-of-Africa (OOA) dispersal ~50,000 years ago is characterized by a series of founder events as modern humans expanded into multiple continents. Population genetics theory predicts an increase of mutational load in populations undergoing serial founder effects during range expansions. To test this hypothesis, we have sequenced full genomes and high-coverage exomes from 7 geographically divergent human populations from Namibia, Congo, Algeria, Pakistan, Cambodia, Siberia and Mexico. We find that individual genomes vary modestly in the overall number of predicted deleterious alleles. We show via spatially explicit simulations that the observed distribution of deleterious allele frequencies is consistent with the OOA dispersal, particularly under a model where deleterious mutations are recessive. We conclude that there is a strong signal of purifying selection at conserved genomic positions within Africa, but that many predicted deleterious mutations have evolved as if they were neutral during the expansion out of Africa. Under a model where selection is inversely related to dominance, we show that OOA populations are likely to have a higher mutation load due to increased allele frequencies of nearly neutral variants that are recessive or partially recessive.

Genomics↗

bioRxiv2014

Inference of evolutionary forces acting on human biological pathways

Because natural selection is likely to act on multiple genes underlying a given phenotypic trait, we study here the potential effect of ongoing and past selection on the genetic diversity of human biological pathways. We first show that genes included in gene sets are generally under stronger selective constraints than other genes and that their evolutionary response is correlated. We then introduce a new procedure to detect selection at the pathway level based on a decomposition of the classical McDonald-Kreitman test extended to multiple genes. This new test, called 2DNS, detects outlier gene sets and takes into account past demographic effects as well as evolutionary constraints specific to gene sets. Selective forces acting on gene sets can be easily identified by a mere visual inspection of the position of the gene sets relative to their 2D null distribution. We thus find several outlier gene sets that show signals of positive, balancing, or purifying selection, but also others showing an ancient relaxation of selective constraints. The principle of the 2DNS test can also be applied to other genomic contrasts. For instance, the comparison of patterns of polymorphisms private to African and non-African populations reveals that most pathways show a higher proportion of non-synonymous mutations in non-Africans than in Africans, potentially due to different demographic histories and selective pressures.

Evolutionary Biology↗