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Radical environmental change that provokes population decline can impose constraints on the sources of genetic variation that may enable evolutionary rescue. Adaptive toxicant resistance has rapidly evolved in Gulf killifish (Fundulus grandis) that occupy polluted habitats. We show that resistance scales with pollution level and negatively correlates with inducibility of aryl hydrocarbon receptor (AHR) signaling. Loci with the strongest signatures of recent selection harbor genes regulating AHR signaling. Two of these loci introgressed recently (18 to 34 generations ago) from Atlantic killifish (F. heteroclitus). One introgressed locus contains a deletion in AHR that confers a large adaptive advantage [selection coefficient (s) = 0.8]. Given the limited migration of killifish, recent adaptive introgression was likely mediated by human-assisted transport. We suggest that interspecies connectivity may be an important source of adaptive variation during extreme environmental change.

Parallel adaptation provides valuable insight into the predictability of evolutionary change through replicated natural experiments. A steadily increasing number of studies have demonstrated genomic parallelism, yet the magnitude of this parallelism varies depending on whether populations, species, or genera are compared. This led us to hypothesize that the magnitude of genomic parallelism scales with genetic divergence between lineages, but whether this is the case and the underlying evolutionary processes remain unknown. Here, we resequenced seven parallel lineages of two Arabidopsis species, which repeatedly adapted to challenging alpine environments. By combining genome-wide divergence scans with model-based approaches, we detected a suite of 151 genes that show parallel signatures of positive selection associated with alpine colonization, involved in response to cold, high radiation, short season, herbivores, and pathogens. We complemented these parallel candidates with published gene lists from five additional alpine Brassicaceae and tested our hypothesis on a broad scale spanning ∼0.02 to 18 My of divergence. Indeed, we found quantitatively variable genomic parallelism whose extent significantly decreased with increasing divergence between the compared lineages. We further modeled parallel evolution over the Arabidopsis candidate genes and showed that a decreasing probability of repeated selection on the same standing or introgressed alleles drives the observed pattern of divergence-dependent parallelism. We therefore conclude that genetic divergence between populations, species, and genera, affecting the pool of shared variants, is an important factor in the predictability of genome evolution.

Many longstanding questions in evolution concern the major forces that shape genetic variation in natural populations: natural selection, genetic drift, mutation, gene flow, and recombination. Their interaction determines the means by which populations adapt and explains patterns of genetic and phenotypic variation within and among populations. In this dissertation, I use recent developments in population genetics to study the genomic signatures of these outcomes and their implications for inferring the history of adaptation and predicting phenotypes.In chapters 1 and 2, I focus on the process of adaptive introgression, whereby selection favors the spread of alleles introduced by gene flow from another species. For both of these chapters, I develop methods based on coalescent theory that use recombination as a signal to understand how and when introgressed alleles facilitated adaptation to new environments. In chapter 1, I analyzed both ancient- and present-day DNA samples from humans and Neanderthals, determining genomic regions where Neanderthal introgression provided standing variation for future adaptation in human populations. In chapter 2, I analyzed samples from two sister killifish species in which some populations can survive extremely toxic waters from pollution. In resistant Fundulus grandis populations of the Houston ship channel, I identified cases of extremely strong selection acting on rare introgressed variation that was introduced recently from a resistant Fundulus heteroclitus population along the Atlantic coast. Together, these chapters uncover the selection pressures acting on populations and highlight that admixture between closely related species can be a source of adaptive variation immediately and in the long term.In chapter 3, I provide an evolutionary perspective on the limitations of genome-wide association study results to understand complex trait variation in understudied populations. I model how mutation, stabilizing selection, and genetic drift interact to shape quantitative trait variation and quantify their implications for phenotype prediction across populations when ascertaining underlying genetic variation in a subset of populations.The combination of theoretical models and analysis of population genomic data in this dissertation provide a rich investigation into the genetics of adaptation and limitations of common approaches in understanding the relationship between genetic and phenotypic variation.

Given the many loci uncovered by genome-wide association studies (GWAS), polygenic scores have become central to the drive for genomic medicine and have spread into various areas including evolutionary studies of adaptation. While promising, these scores are fraught with issues of portability across populations, due to the misestimation of effect sizes and missing causal loci across populations not represented in large-scale GWAS. The poor portability of polygenic scores at first seems at odds with the view that much of common genetic variation is shared among populations (Lewontin 1972). Here we investigate one potential cause of this discrepancy: phenotypic stabilizing selection drives the turnover of genetic variation shared between populations at causal loci. Somewhat counter-intuitively, while stabilizing selection to the same optimum phenotype leads to lower phenotypic differentiation among populations, it increases genetic differentiation at GWAS loci and reduces the portability of polygenic scores constructed for unrepresented populations. We also find that stabilizing selection can lead to potentially misleading signals of the differentiation of average polygenic scores among populations. We extend our baseline model to investigate the impact of pleiotropy, gene-by-environment interactions, and directional selection on polygenic score predictions. Our work emphasizes stabilizing selection as a null evolutionary model to understand patterns of allele frequency differentiation and its impact on polygenic score portability and differentiation. Competing Interest Statement The authors have declared no competing interest.

Abstract Admixture has the potential to facilitate adaptation by providing alleles that are immediately adaptive in a new environment or by simply increasing the long term reservoir of genetic diversity for future adaptation. A growing number of cases of adaptive introgression are being identified in species across the tree of life, however the timing of selection, and therefore the importance of the different evolutionary roles of admixture, is typically unknown. Here, we investigate the spatio-temporal history of selection favoring Neanderthal-introgressed alleles in modern human populations. Using both ancient and present-day samples of modern humans, we integrate the known demographic history of populations, namely population divergence and migration, with tests for selection. We model how a sweep placed along different branches of an admixture graph acts to modify the variance and covariance in neutral allele frequencies among populations at linked loci. Using a method based on this model of allele frequencies, we study previously identified cases of Neanderthal adaptive introgression. From these, we identify cases in which Neanderthal introgressed alleles were quickly beneficial and other cases in which they persisted at low frequency for some time. For some of the alleles that persisted at low frequency, we show that selection likely independently favored them later on in geographically separated populations. Our work highlights how admixture with ancient hominins has contributed to modern human adaptation and contextualizes observed levels of Neanderthal ancestry in present-day and ancient samples. Competing Interest Statement The authors have declared no competing interest.

Abstract Parallel adaptation provides valuable insight into the predictability of evolutionary change through replicated natural experiments. A steadily increasing number of studies have demonstrated genomic parallelism, yet the magnitude of this parallelism varies depending on whether populations, species or genera are compared. This led us to hypothesize that the magnitude of genomic parallelism scales with genetic divergence between lineages, but whether this is the case and the underlying evolutionary processes remain unknown. Here, we resequenced seven parallel lineages of two Arabidopsis species which repeatedly adapted to challenging alpine environments. By combining genome-wide divergence scans with model-based approaches we detected a suite of 151 genes that show parallel signatures of positive selection associated with alpine colonization, involved in response to cold, high radiation, short season, herbivores and pathogens. We complemented these parallel candidates with published gene lists from five additional alpine Brassicaceae and tested our hypothesis on a broad scale spanning ~ 0.02 to 18 million years of divergence. Indeed, we found quantitatively variable genomic parallelism whose extent significantly decreased with increasing divergence between the compared lineages. We further modeled parallel evolution over the Arabidopsis candidate genes and showed that a decreasing probability of repeated selection of the same standing or introgressed alleles drives the observed pattern of divergence-dependent parallelism. We therefore conclude that genetic divergence between populations, species and genera, affecting the pool of shared variants, is an important factor in the predictability of genome evolution. Significance statement Repeated evolution tends to be more predictable. The impressive spectrum of recent reports on genomic parallelism, however, revealed that the fraction of the genome that evolves in parallel largely varies, possibly reflecting different evolutionary scales investigated. Here, we demonstrate divergence-dependent parallelism using a comprehensive genome-wide dataset comprising 12 cases of parallel alpine adaptation and identify decreasing probability of adaptive re-use of genetic variation as the major underlying cause. This finding empirically demonstrates that evolutionary predictability is scale dependent and suggests that availability of pre-existing variation drives parallelism within and among populations and species. Altogether, our results inform the ongoing discussion about the (un)predictability of evolution, relevant for applications in pest control, nature conservation, or the evolution of pathogen resistance. Competing Interest Statement The authors have declared no competing interest. Footnotes * Classification BIOLOGICAL SCIENCES: Evolution

Studies of ciliopathies have served in elucidating much of our knowledge of structure and function of primary cilia. We report humans with Bardet-Biedl syndrome who display intellectual disability, retinitis pigmentosa, obesity, short stature and brachydactyly, stemming from a homozyogous truncation mutation in SCAPER, a gene previously associated with mitotic progression. Our findings, based on linkage analysis and exome sequencing studies of two remotely related large consanguineous families, are in line with recent reports of SCAPER variants associated with intellectual disability and retinitis pigmentosa. Using immuno-fluorescence and live cell imaging in NIH/3T3 fibroblasts and SH-SY5Y neuroblastoma cell lines over-expressing SCAPER, we demonstrate that both wild type and mutant SCAPER are expressed in primary cilia and co-localize with tubulin, forming bundles of microtubules. While wild type SCAPER was rarely localized along the ciliary axoneme and basal body, the aberrant protein remained sequestered to the cilia, mostly at the ciliary tip. Notably, longer cilia were demonstrated both in human affected fibroblasts compared to controls, as well as in NIH/3T3 cells transfected with mutant versus wildtype SCAPER. As SCAPER expression is known to peak at late G1 and S phase, overlapping the timing of ciliary resorption, our data suggest a possible role of SCAPER in ciliary dynamics and disassembly, also affecting microtubule-related mitotic progression. Thus, we outline a human ciliopathy syndrome and demonstrate that it is caused by a mutation in SCAPER, affecting primary cilia.

Currently, table olives, unlike oil olives, are harvested manually. Shortage of manpower and increasing labor costs are the main incentives to mechanizing the harvesting of table olives. One of the major limiting factors in adopting mechanical harvest of table olives is the injury to fruit during mechanical harvest, which lowers the quality of the final product. In this study, we used the Israeli germplasm collection of olive cultivars at the Volcani Institute to screen the sensitivity of many olive cultivars to browning in response to injury. The browning process after induced mechanical injury was characterized in 106 olive cultivars. The proportional area of brown coloring after injury, compared to the total fruit surface area, ranged from 0 to 83.61%. Fourteen cultivars were found to be resistant to browning and did not show any brown spot 3 h after application of pressure. Among them, there are some cultivars that can serve as table olives. The different response to mechanical damage shown by the cultivars could be mainly due to genetic differences. Mesocarp cells in the fruits of the sensitive cultivars were damaged and missing the cell wall as a result of the applied pressure. The cuticles of resistant cultivars were thicker compared to those of susceptible cultivars. Finally, we showed that the browning process is enzymatic. We suggest cuticle thickness as an indicator of table olive cultivars suitable for mechanical harvest. A shift to browning-resistant cultivars in place of the popular cultivars currently in use will enable the mechanical harvest of table olive without affecting fruit quality.