Reconstructing the history of founder events using genome-wide patterns of allele sharing across individuals

Abstract

Founder events play a critical role in shaping genetic diversity, impacting the fitness of a species and disease risk in humans. Yet our understanding of the prevalence and distribution of founder events in humans and other species remains incomplete, as most existing methods for characterizing founder events require large sample sizes or phased genomes. To learn about the frequency and evolutionary history of founder events, we introduce ASCEND (Allele Sharing Correlation for the Estimation of Non-equilibrium Demography), a flexible two-locus method to infer the age and strength of founder events. This method uses the correlation in allele sharing across the genome between pairs of individuals to recover signatures of past bottlenecks. By performing coalescent simulations, we show that ASCEND can reliably estimate the parameters of founder events under a range of demographic scenarios, with genotype or sequence data. We apply ASCEND to ~5,000 worldwide human samples (~3,500 present-day and ~1,500 ancient individuals), and ~1,000 domesticated dog samples. In both species, we find pervasive evidence of founder events in the recent past. In humans, over half of the populations surveyed in our study had evidence for a founder events in the past 10,000 years, associated with geographic isolation, modes of sustenance, and historical invasions and epidemics. We document that island populations have historically maintained lower population sizes than continental groups, ancient hunter-gatherers had stronger founder events than Neolithic Farmers or Steppe Pastoralists, and periods of epidemics such as smallpox were accompanied by major population crashes. Many present-day groups--including Central & South Americans, Oceanians and South Asians--have experienced founder events stronger than estimated in Ashkenazi Jews who have high rates of recessive diseases due to their history of founder events. In dogs, we uncovered extreme founder events in most groups, more than ten times stronger than the median strength of founder events in humans. These founder events occurred during the last 25 generations and are likely related to the establishment of dog breeds during Victorian times. Our results highlight a widespread history of founder events in humans and dogs, and provide insights about the demographic and cultural processes underlying these events.

Population Histories and Genomic Diversity of South American Natives

“…Lastly, contact with the Europeans and the colonization of the American continent led to massive depopulation of the indigenous people caused by the introduction of new diseases (e.g., smallpox), enslavement, warfare, disruption of subsistence strategies, and forced displacement from territories, among other processes ( Montenegro and Stephens 2006 ; Adhikari et al 2017 ). To evaluate the effect of these population bottlenecks on the genetic diversity of indigenous populations of the Americas, inferring when they occurred and how strong they were, we applied ASCEND ( Tournebize et al 2020 ) to all populations with more than five unrelated individuals ( fig. 6 A ).…”

“…Some populations were also analyzed in clusters of speakers of languages from the same linguistic families (to reach the minimum sample size required for the analysis). For each population and cluster, the Founder Intensity (FI; an estimate of the genetic drift strength caused by a bottleneck) and Founder Age (FA; inferred date of the bottleneck) were estimated, along with the associated 95% confidence intervals ( Tournebize et al 2020 ).…”

“… The postcontact population collapse and Native American effective population size (N e ) histories. ( A ) We applied the ASCEND ( Tournebize et al 2020 ) method to every Native American group with more than 5 unrelated samples (and also to some clusters of groups to reach the minimum sample size of 5, see supplementary fig. S15 , Supplementary Material online ), and we also selected the groups with an estimated FA lower than 1000 BP.…”

“…We then used the ASCEND software ( Tournebize et al 2020 ) to infer the age and intensity of the bottleneck events on the Native American groups. First, we selected the Native Americans from the complete data set, then we pruned markers and samples with more than 5% of missing data (no samples were removed due to this criterion).…”

“…The cross-population correlation with an outgroup is subtracted from this intra-population correlation to exclude the effect of ancestral allele sharing. A random sample of 15 individuals from the complete data set was used as the outgroup population as in Tournebize et al (2020) .…”