Genus Danio includes zebrafish (Danio rerio) and several other phenotypically diverse species. To understand the history of these species and how they acquired the genetic differences underlying their diverse phenotypes, I performed two phylogenomic studies using Restriction-Site Associated DNA Sequencing and DNA hybridization-based exome enrichment. The results of these studies highlight important methodological considerations applicable to future experiments across taxa. Furthermore, these studies provide detailed understanding of the relationships within Danio including extensive introgression between lineages. The extent of introgression varies across the genome with regions of high recombination at the ends of chromosomes having the most evidence for introgression. Together, this work gives vital insight into the history of a model organism and the evolutionary processes that give rise to phenotypic diversity.

Problems of population genetics are magnified by problems of big data. My dissertation spans the disciplines of computer science and population genetics, leveraging computational approaches to biological problems to address issues in genomics research. In this dissertation I develop more efficient metric search algorithms. I also show that vast majority of the genomes of great apes are impacted by the forces of natural selection. Finally, I introduce a heuristic to identify neutralomes—regions that are evolving with minimal selective pressures—and use these neutralomes for inferences on effective population size in great apes. We begin with a formal and far-reaching problem that impacts a broad array of disciplines including biology and computer science; the 𝑘-nearest neighbors problem in generalized metric spaces. The 𝑘-nearest neighbors (𝑘-NN) problem is deceptively simple. The problem is as follows: given a query q and dataset D of size 𝑛, find the 𝑘-closest points to q. This problem can be easily solved by algorithms that compute 𝑘th order statistics in O(𝑛) time and space. It follows that if D can be ordered, then it is perhaps possible to solve 𝑘-NN queries in sublinear time. While this is not possible for an arbitrary distance function on the points in D, I show that if the points are constrained by the triangle inequality (such as with metric spaces), then the dataset can be properly organized into a dispersion tree (Appendix A). Dispersion trees are a hierarchical data structure that is built around a large dispersed set of points. Dispersion trees have construction times that are sub-quadratic (O(𝑛¹·⁵ log⁡ 𝑛)) and use O(𝑛) space, and they use a provably optimal search strategy that minimizes the number of times the distance function is invoked. While all metric data structures have worst-case O(𝑛) search times, dispersion trees have average-case search times that are substantially faster than a large sampling of comparable data structures in the vast majority of spaces sampled. Exceptions to this include extremely high dimensional space (d>20) which devolve into near-linear scans of the dataset, and unstructured low-dimensional (d<6) Euclidean spaces. Dispersion trees have empirical search times that appear to scale as O(𝑛ᶜ) for 0<c<1. As solutions to the 𝑘-NN problem are in general too slow to be used effectively in the arena of big data in genomics, it is my hope that dispersion trees may help lift this barrier. With source-code that is freely available for academic use, dispersion trees may be useful for nearest neighbor classification problems in machine learning, fast read-mapping against a reference genome, and as a general computational tool for problems such clustering. Next, I turn to problems in population genomics. Genomic patterns of diversity are a complex function of the interplay between demographics, natural selection and mechanistic forces. A central tenet of population genetics is the neutral theory of molecular evolution which states the vast majority of changes at the molecular level are (relatively) selectively neutral; that is, they do not effect fitness. A corollary of the neutral theory is that the frequency of most alleles in populations are dictated by neutral processes and not selective processes. The forces of natural selection impact not just the site of selection, but linked neutral sites as well. I proposed an empirical assessment of the extents of linked selection in the human genome (Appendix B). Recombination decouples sites of selection from the genomic background, thus it serves to mitigate the effects of linked selection. I use two metrics on recombination, both the minimum genetic distance to genes and local rates of recombination, to parse the effects of linked selection into selection from genic and nongenic sources in the human genome. My empirical assessment shows profound linked selective effects from nongenic sources, with these effects being greater than that of genic sources on the autosomes, as well as generally greater effects on the X chromosome than on the autosomes. I quantify these trends using multiple linear regression, and then I model the effects of linked selection to conserved elements across the whole of the genome. Places predicted to be neutral by my model do not, unlike the vast majority of the genome, show these linked selective effects. This demonstrates that linkage to these regulatory elements, and not some other mechanistic force, accounts for our findings. Further, neutrally evolving regions are extremely rare (~1%) in the genome, and despite generally larger linked selective effects on the X chromosome, the size of this “neutralome” is proportionally larger on the X chromosome than on the autosomes. To account for this and to extend my findings to other great apes I improve on my procedure to find neutralomes, and apply this procedure to the genome of humans, Nigerian chimpanzees, bonobos, and western lowland gorillas (Appendix C). In doing so I show that like humans, these other apes are also enormously impacted by linked selection, with their neutralomes being substantially smaller than the neutralomes of humans. I then use my genomic predictions on neutrality to see how the landscape of linked selection changes across the X chromosome and the autosomes in regions close to, and far from, genes. While I had previously demonstrated the linked selective forces near genes are stronger on the X chromosome than on the autosomes in these taxa, I show that regions far from genes show the opposite; regions far from genes show more selection from noncoding targets on the autosomes than on the X chromosome. This finding is replicated across our great ape samples. Further, inferences on the relative effective population size of the X chromosome and the autosomes both near and far from genes can be biased as a result.

Species are vital entities in biology. Species are generally considered to be discrete entities, consisting of a group of (usually interbreeding) individuals that are similar in phenotype and genetic composition, yet differ in significant ways from other species. The study of speciation has focussed on understanding general evolutionary mechanisms involved in the accumulation of differences both at the genetic and phenotypic level. In this thesis, I investigate incipient speciation, an early stage of divergence towards evolutionary independence in closely related natural populations. I make ample use of recent advances in sequencing technology that allow 1) characterizing phenotypic divergence at the level of the transcriptome and 2) delineate patterns of genetic variation at genome-scale from which processes are inferred by using principles of population genetic theory. In the first paper, we assembled a draft genome of the hooded crow and investigated population differentiation across a famous European hybrid zone. Comparing sequence differentiation peaks between and within the colour morphs, we could identify regions of the genome that show differentiation only between colour morphs and that could be related to gene expression profiles of the melanogenesis pathway coding for colour differences. The second paper expands on the first paper in that it includes crow population samples from across the entire Palaearctic distribution spanning two additional zones of contact between colour morphs. The results suggest that regions associated with selection against gene flow between colour morphs were largely idiosyncratic to each contact zone and emerged against a background of conserved 'islands of differentiation' due to shared linked selection. The third paper focusses on five killer whale ecotypes with distinct feeding and habitat specific adaptations. Differing levels of sequence differentiation between these ecotypes places them along a speciation continuum and provides a unique temporal cross-section of the speciation process. Using genome scans we identified regions of the genome that show ecotype specific differentiation patterns which might contain candidate genes involved in adaptation. In the fourth and final paper, I assumed a comparative genomic perspective to the problem of heterogeneous genomic differentiation during population divergence. The relatively high correlations in the diversity landscapes as well as differentiation patterns between crow, flycatcher and Darwin's Finch populations is best explained by conservation in broad-scale recombination rate and/or  association with telomeres and centromeres conducive to shared, linked selection.

Individuals vary from each other in their genetic content. Genetic diversity is at the core of the evolutionary theory. Rooted in a solid theoretical framework developed as early as the 1930s, current empirical observations of genomic diversity became possible due to technological advances. These measurements, originally based on a few gene sequences from several individuals, are becoming possible at the genome scale for entire populations. We can now explore how evolutionary forces shape diversity levels along different parts of the genome. In this thesis, I focus on the variation in levels of diversity within genomes using avian systems and in particular that of the collared flycatcher (Ficedula albicollis). First, I describe the variation in genetic diversity along the genome of the collared flycatcher and compare it to the amount of variation in diversity across individuals within the population. I provide guidelines on how a small number of makers can capture the extent of variability in a population. Second, I investigate the stability of the local levels of diversity in the genome across evolutionary time scales by comparing collared flycatcher to the hooded crow (Corvus (corone) corone). Third, I study how selection can maintain variation through pervasive evolutionary conflict between sexes. Lastly, I explore how shifts in genome-wide variant frequencies across few generations can be utilised to estimate the effective size of population.

Abstract Demographic history and natural selection are central forces shaping the genetic diversity of populations. Knowledge on these forces increases understanding of processes shaping genetic variability of populations. In this PhD thesis I investigated demographic history and selection in multiple populations of Arabidopsis lyrata, an outcrossing herbaceous plant species of the Brassicaceae family. Due to its wide distribution in the temperate and boreal regions, A. lyrata serves as a good model system to study population genetic consequences of colonization of northern latitudes. The first aim of this study was to characterize the demographic and colonization history of the species using site frequency spectra estimated from whole-genome diversity data. Another aim was to detect genetic loci targeted by recent selective sweeps at genome-wide scale as well as at candidate flowering time genes. Patterns of genome-wide selection at linked sites (linked selection) were also compared between populations of Capsella grandiflora and A. lyrata with contrasting demographic histories. Evidence for strong effective population size decline in the past few hundred thousand years was detected in A. lyrata populations species-wide. This study also suggests recent Scandinavian colonization from an unknown refugium, distinct from the Central European source population. Selection analyses revealed loci targeted by positive selection in two Scandinavian lineages after the recent population split as well as selective sweeps in flowering time genes in the colonizing populations. In comparison with the studied C. grandiflora population, the Norwegian A. lyrata population had weaker purifying selection and no evidence for reduction of diversity around genes was found. This thesis offers novel information on species colonization history and its genome-wide effects, which is important for understanding the framework of local adaptation. / Tiivistelmä Populaation demografinen historia ja luonnonvalinta ovat keskeisiä populaation perinnöllisen muuntelun muokkaajia. Näiden tekijöiden tutkimus on tärkeää eliöiden sopeutumisen ymmärtämiselle. Tässä väitöskirjassa tutkin demografista historiaa ja valintaa monivuotisen ristisiittoiseen ruohovartisen Brassicaceae-heimon kasvilajin idänpitkäpalon (Arabidopsis lyrata) useissa eri populaatioissa. Idänpitkäpalko on erinomainen mallilaji pohjoiseen ympäristöön sopeutumisen tutkimukseen, koska sen toisistaan eristäytyneet paikalliset populaatiot ovat levittäytyneet laajalle boreaalisella ja lauhkealla ilmastovyöhykkeellä. Tutkimuksen tarkoituksena oli luonnehtia populaatioiden demografista historiaa ja kolonisaatioreittejä käyttäen koko perimän laajuisesta muunteluaineistosta estimoituja alleelifrekvenssispektrejä. Lisäksi koko perimän laajuista aineistoa sekä kukkimisaikaa ohjaavien geenien sekvenssejä käytettiin positiivisen luonnonvalinnan merkkien tunnistukseen. Genominlaajuista kytkeytynyttä valintaa vertailtiin toiseen ristisiittoiseen Brassicaceae-heimon lajin Capsella grandifloran populaatioon, jonka demografinen historia poikkeaa huomattavasti tutkituista idänpitkäpalon populaatioista. Tutkimuksessa havaittiin, että kaikissa tutkituissa idänpitkäpalon populaatioissa tehollinen populaatiokoko oli pienentynyt viimeisen muutaman sadantuhannen vuoden aikana. Kolonisaatiohistorian tarkastelu osoitti, että idänpitkäpalon skandinaaviset populaatiot ovat todennäköisesti peräisin keskieurooppalaisesta refugiosta erillisestä läntisestä refugiosta. Skandinavian kolonisaation yhteydessä vaikuttaneen positiivisen luonnonvalinnan merkkejä havaittiin useissa eri genomin osissa sekä erityisesti valojaksoa mittaavissa geeneissä. Tämä kertoo erilaisiin valojaksoihin sopeutumisen tärkeydestä skandinaavisen kolonisaation yhteydessä. Verrattuna tutkittuun C. grandifloran populaatioon, idänpitkäpalolla puhdistavan valinnan havaittiin olevan heikompaa ja muuntelun vähenemistä geenien ympärillä ei havaittu. Tämä tutkimus tarjoaa uutta tietoa Skandinavian kolonisaatiohistoriasta ja sen genominlaajuisista vaikutuksista. Tutkimuksessa tuotettua tietoa voidaan hyödyntää paikallisen sopeutumisen ymmärtämisessä.