Statistical inference on evolutionary processes in Alpine ibex (Capra ibex): mutation, migration and selection

The thesis begins with a general introduction to population genetics in chapter 1. I review the fundamental processes of evolution - mutation, recombination, selection, gene flow and genetic drift - and give an overview of Bayesian inference in statistical population genetics. Later, I introduce the studied species, Alpine ibex (Capra ibex ), and its recent history. This history is intimately linked to the structured population in the Swiss Alps that provides the source of genetic data for this thesis. A particular focus is devoted to approximate Bayesian computation (ABC) in chapter 2, a method of inference that has become important over the last 15 years and is convenient for complex problems of inference. In chapter 3, the biological focus is on estimating the distribution of mutation rates across neutral genetic variation (microsatellites), and on inferring the proportion of male ibex that obtain access to matings each breeding season. The latter is an important determinant of genetic drift. Methodologically, I compare different methods for the choice of summary statistics in ABC. One of the approaches proposed by collaborators and me and based on boosting (a technique developed in machine learning) is found to perform best in this case. Applying that method to microsatellite data from Alpine ibex, I estimate the scaled ancestral mutation rate (THETA anc = 4Neu) to about 1:288, and find that most of the variation across loci of the ancestral mutation rate u is between 7.7*10^-4 and 3.5*10^-3. The proportion of males with access to matings per breeding season is estimated to about 21%. Chapter 4 is devoted to the estimation of migration rates between a large number of pairs of populations. Again, I use ABC for inference. Estimating all rates jointly comes with substantial methodological problems. Therefore, I assess if, by dividing the whole problem into smaller ones and assuming that those are approximately independent, more accuracy may be achieved overall. The net accuracy of the second approach increases with the number of migration rates. Applying that approach to microsatellite data from Alpine ibex, and accounting for the possibility that a model without migration could also explain the data, I find no evidence for substantial gene flow via migration, except for one pair of demes in one direction. While chapters 3 and 4 deal with neutral variation, in chapter 5 I investigate if an allele of the Major Histocompatibility Complex (MHC) has been under selection over the last ten generations. Short- and medium-term methods for detecting signals of selection are combined. For the medium-term analysis, I adapt a matrix iteration approach that allows for joint estimation of the initial allele frequency, the dominance coefficient, and the strength of selection. The focal MHC allele is shared with domestic goat, and an interesting side issue is if this reflects an ancestral polymorphism or is due to recent introgression via hybridization. I find most evidence for asymmetric overdominance (selection coefficient s: 0.974; equilibrium frequency: 0.125) or directional selection against the `goat' allele (s: 0.5) with partial recessivity. Both scenarios suggest a disadvantage of the `goat' homozygote, but differ in the relative fitness of the heterozygotes. Overall, two aspects play a dominating role in this thesis: the biological questions and the process of inference. They are linked, yet while the proximate motivation for the biological component is given by a specific system - the structured population of Alpine ibex in the Swiss Alps - the methods used and advanced here are fairly general and may well be applied in different contexts

Demographically explicit scans for barriers to gene flow using gIMble

Identifying regions of the genome that act as barriers to gene flow between recently diverged taxa has remained challenging given the many evolutionary forces that generate variation in genetic diversity and divergence along the genome, and the stochastic nature of this variation. Progress has been impeded by a conceptual and methodological divide between analyses that infer the demographic history of speciation and genome scans aimed at identifying locally maladaptive alleles i.e. genomic barriers to gene flow. Here we implement genomewide IM blockwise likelihood estimation (), a composite likelihood approach for the quantification of barriers, that bridges this divide. This analytic framework captures background selection and selection against barriers in a model of isolation with migration (IM) as heterogeneity in effective population size (N$_{e}$) and effective migration rate (m$_{e}$), respectively. Variation in both effective demographic parameters is estimated in sliding windows via pre-computed likelihood grids. includes modules for pre-processing/filtering of genomic data and performing parametric bootstraps using coalescent simulations. To demonstrate the new approach, we analyse data from a well-studied pair of sister species of tropical butterflies with a known history of post-divergence gene flow: Heliconius melpomene and H. cydno. Our analyses uncover both large-effect barrier loci (including well-known wing-pattern genes) and a genome-wide signal of a polygenic barrier architecture

Comparative evaluation of the MAPlex, Precision ID Ancestry Panel, and VISAGE Basic Tool for biogeographical ancestry inference

Biogeographical ancestry (BGA) inference from ancestry-informative markers (AIMs) has strong potential to support forensic investigations. Over the past two decades, several forensic panels composed of AIMs have been developed to predict ancestry at a continental scale. These panels typically comprise fewer than 200 AIMs and have been designed and tested with a limited set of populations. How well these panels recover patterns of genetic diversity relative to larger sets of markers, and how accurately they infer ancestry of individuals and populations not included in their design remains poorly understood. The lack of comparative studies addressing these aspects makes the selection of appropriate panels for forensic laboratories difficult. In this study, the model-based genetic clustering tool STRUCTURE was used to compare three popular forensic BGA panels: MAPlex, Precision ID Ancestry Panel (PIDAP), and VISAGE Basic Tool (VISAGE BT) relative to a genome-wide reference set of 10k SNPs. The genotypes for all these markers were obtained for a comprehensive set of 3957 individuals from 228 worldwide human populations. Our results indicate that at the broad continental scale (K = 6) typically examined in forensic studies, all forensic panels produced similar genetic structure patterns compared to the reference set (G′ ≈ 90%) and had high classification performance across all regions (average AUC-PR > 97%). However, at K = 7 and K = 8, the forensic panels displayed some region-specific clustering deviations from the reference set, particularly in Europe and the region of East and South-East Asia, which may be attributed to differences in the design of the respective panels. Overall, the panel with the most consistent performance in all regions was VISAGE BT with an average weighted AUC̅W score of 96.26% across the three scales of geographical resolution investigated

Geographic Variation in Genomic Signals of Admixture Between Two Closely Related European Sepsid Fly Species.

UNLABELLED The extent of interspecific gene flow and its consequences for the initiation, maintenance, and breakdown of species barriers in natural systems remain poorly understood. Interspecific gene flow by hybridization may weaken adaptive divergence, but can be overcome by selection against hybrids, which may ultimately promote reinforcement. An informative step towards understanding the role of gene flow during speciation is to describe patterns of past gene flow among extant species. We investigate signals of admixture between allopatric and sympatric populations of the two closely related European dung fly species Sepsis cynipsea and S. neocynipsea (Diptera: Sepsidae). Based on microsatellite genotypes, we first inferred a baseline demographic history using Approximate Bayesian Computation. We then used genomic data from pooled DNA of natural and laboratory populations to test for past interspecific gene flow based on allelic configurations discordant with the inferred population tree (ABBA-BABA test with D-statistic). Comparing the detected signals of gene flow with the contemporary geographic relationship among interspecific pairs of populations (sympatric vs. allopatric), we made two contrasting observations. At one site in the French Cevennes, we detected an excess of past interspecific gene flow, while at two sites in Switzerland we observed lower signals of past microsatellite genotypes gene flow among populations in sympatry compared to allopatric populations. These results suggest that the species boundaries between these two species depend on the past and/or present eco-geographic context in Europe, which indicates that there is no uniform link between contemporary geographic proximity and past interspecific gene flow in natural populations. SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s11692-023-09612-5

Geographic Variation in Genomic Signals of Admixture Between Two Closely Related European Sepsid Fly Species

The extent of interspecific gene flow and its consequences for the initiation, maintenance, and breakdown of species barriers in natural systems remain poorly understood. Interspecific gene flow by hybridization may weaken adaptive divergence, but can be overcome by selection against hybrids, which may ultimately promote reinforcement. An informative step towards understanding the role of gene flow during speciation is to describe patterns of past gene flow among extant species. We investigate signals of admixture between allopatric and sympatric populations of the two closely related European dung fly species Sepsis cynipsea and S. neocynipsea (Diptera: Sepsidae). Based on microsatellite genotypes, we first inferred a baseline demographic history using Approximate Bayesian Computation. We then used genomic data from pooled DNA of natural and laboratory populations to test for past interspecific gene flow based on allelic configurations discordant with the inferred population tree (ABBA–BABA test with D-statistic). Comparing the detected signals of gene flow with the contemporary geographic relationship among interspecific pairs of populations (sympatric vs. allopatric), we made two contrasting observations. At one site in the French Cevennes, we detected an excess of past interspecific gene flow, while at two sites in Switzerland we observed lower signals of past microsatellite genotypes gene flow among populations in sympatry compared to allopatric populations. These results suggest that the species boundaries between these two species depend on the past and/or present eco-geographic context in Europe, which indicates that there is no uniform link between contemporary geographic proximity and past interspecific gene flow in natural populations

si_files_SA.tar

SLiM simulation

si_files_SA.tar

SLiM simulation

Census sizes of Alpine ibex demes in the Swiss Alps

This file contains census population sizes of Alpine ibex in the Swiss Alps from 1906 to 2007

The Strength of Selection against Neanderthal Introgression.

Hybridization between humans and Neanderthals has resulted in a low level of Neanderthal ancestry scattered across the genomes of many modern-day humans. After hybridization, on average, selection appears to have removed Neanderthal alleles from the human population. Quantifying the strength and causes of this selection against Neanderthal ancestry is key to understanding our relationship to Neanderthals and, more broadly, how populations remain distinct after secondary contact. Here, we develop a novel method for estimating the genome-wide average strength of selection and the density of selected sites using estimates of Neanderthal allele frequency along the genomes of modern-day humans. We confirm that East Asians had somewhat higher initial levels of Neanderthal ancestry than Europeans even after accounting for selection. We find that the bulk of purifying selection against Neanderthal ancestry is best understood as acting on many weakly deleterious alleles. We propose that the majority of these alleles were effectively neutral-and segregating at high frequency-in Neanderthals, but became selected against after entering human populations of much larger effective size. While individually of small effect, these alleles potentially imposed a heavy genetic load on the early-generation human-Neanderthal hybrids. This work suggests that differences in effective population size may play a far more important role in shaping levels of introgression than previously thought