CONSEQUENCES OF BOTTLENECKS AND FOUNDER EFFECTS ON GENOMIC DIVERSITY WITHIN HUMAN POPULATIONS

As human history has been characterized by significant effective population size (Ne) reductions (bottlenecks, founder effects), several signs of such events can be nowadays detected in our genome: this work represents a critical review of the most relevant scientific literature on the subject. It’s been explained how Ne reductions influence genetic diversity inducing decrease of heterozygosity, star-like coalescent trees and skewed Site Frequency Spectrums, similarly to selective sweeps. Then, the influence of dominance dynamics has been discussed, showing that beneficial recessive alleles are more likely to decrease in frequency after a bottleneck, while they improve genetic diversity due to hitchhiking effect. Focusing on examples within human populations, the Out-Of-Africa (OAA) dispersal has been described, as it resulted in higher mildly deleterious mutational load as well as in progressive decrease of heterozygosity. In this context proper discussion highlighted how the use of non-allelic-frequence dependent models is necessary for proper results. Furthermore, past demography signs can be detected from the genomic data, such as the post-OAA comeback to Africa of North African populations. Eventually, pseudo-overdominance has been described, as well as its consequences on the genome compared to Ne reductions: in this context, contrasting effects of left-side and right-side SFS skews and genetic diversity have been detected, then possible pseudo-overdominance sites in humans have been cited. In the last chapter, consequences of founder effects on human autosomal recessive disorders (ARD) have been discussed, focusing on how these phenomena can cause higher disease prevalence and lower number of responsible variants. The examples of Finnish Genetic Heritage and Fanconi anemia cases were deepened to show how these events can also prevent other relatively common mutations to be present and how deeply genomic data can be linked to historical events, as the Fanconi anemia main variation has been associated to a founder couple emigrated from France in the 17th century.