Speciation, the evolution of morphologically, behaviorally and/or ecologically distinct lineages from a common ancestor, is the fundamental process generating biodiversity. The rapidly developing field of speciation genomics is challenging traditional views of speciation as a gradual, genome-wide process, and highlighting the role of divergent natural selection in the speciation process. This study investigates morphological evolution and the genomic architecture of speciation in a clade of 12 "munias" in the genus Lonchura, one of the most extraordinary cases of recent and rapid diversification in birds. With a diversity of plumage patterns and replicate examples of closely related species living in sympatry, this group is ideally suited
for addressing fundamental questions about the genomics of speciation. In this study, I (1) test for evidence of character displacement between sympatric species using quantitative measurements of plumage coloration and morphology; (2) examine the structure of genome-wide variation using ddRAD-seq (double-digest Restriction Site Associated DNA sequencing); and (3) investigate the genomic structure of divergence using whole-genome sequencing. I find some evidence for character displacement, particularly in morphometrics and crown coloration. There is also a trend, however, for sympatric species to be more similar in coloration than allopatric species, particularly those that have come into contact more recently. Analysis of 7,043 ddRAD-seq loci reveals evidence of introgression among sympatric populations, with overall genomic variation corresponding more closely to geography than species identity. There is also substantial heterogeneity in genetic structure among mitochondrial, autosomal, and Z-linked markers. Finally, whole-genome sequencing reveals low overall genomic divergence while pinpointing "islands of differentiation" that exhibit elevated divergence between species. Two of these islands overlap genes known to be associated with coloration—Agouti signaling protein (ASIP) and Kit ligand (KITLG)—and allelic variation at these genes is associated with phenotypic traits. I also find evidence of a ~26 million base pair inversion on the Z chromosome, which groups the focal species differently than genome-wide variation. A strongly mosaic pattern of population structure among genomic regions supports a genic view of speciation, in which a small fraction of the genome is involved in the initial divergence of species.

Speciationisusuallyaslowprocessoccurringoverthousandstomillionsofyears.Thismakes speciation research difficult because no direct observation or manipulation is possible. At best, we can gain some insight by inferring the population history and structure in very fine detail by investigating genetic markers in multiple individuals of the nascent species. Today, speciationresearchisinanunprecedentedpositionthankstotheadventofhigh-throughput sequencingmethods,whichmakeiteasier and cheaper than ever before to evaluate multiple markers in many individuals. Speciation is not a straightforward process that happens in the same way every time, but rather a phenomenon occurring when genetic and ecological circumstancesactinginsymphonyultimatelyleadtoreproductiveisolationoftwosubpopula- tions. This is why it is important to study multiple model systems to understand the general principles behind speciation. We worked with two species of nightingales (Luscinia luscinia andL.megarhynchos)thatdivergedapproximately1.8Mya,likelyduetoglacialfluctuations in Europe. Our main goal was to use these new high-throughput sequencing methods to (1) detect interspecific hybrids between the species, (2) estimate levels of interspecific gene flow,(3)findareasofthenightingalegenomethatunderliereproductiveisolationand,finally, (4)...

Population dynamics of large ungulates are complex and vary with fluctuations in factors such as predation, resource availability, human disturbance, and weather (Gaillard et al. 1998, Forrester and Wittmer 2013). These regulating factors exhibit similar effects on ungulate populations by changing vital rates such as birthrate, death rate, emigration or immigration (Gaillard et al. 2000). To better understand the mechanisms influencing population change, it is useful to involve tools from multiple disciplines (Krausman et al. 2013). Here we explore population dynamics of mule deer (Odocoileus hemionus) through the lenses of two distinct fields: population ecology and genomics. In the first chapter we examine the influence of maternal effects on offspring fitness. In the second chapter we present a high-quality, chromosome-level reference genome for mule deer. We expect results from each of these studies to provide valuable resources for continued research and conservation of mule deer.

Many angiosperms have undergone some series of polyploidization events over the course of their evolutionary history. In these genomes, especially those resulting from multiple autopolyploidization, it may be relatively easy to recognize all the sets of n homeologous chromosomes, but it is much harder, if not impossible, to partition these chromosomes into n subgenomes, each representing one distinct genomic component of chromosomes making up the original polyploid. Thus, if we wish to infer the polyploidization history of the genome, we could make use of all the gene trees inferred from the genes in one set of homeologous chromosomes to construct a consensus tree, but there is no evident way of combining the trees from the different sets because we have no labelling of the chromosomes that is known to be consistent across these sets. We suggest here that lacking a consistent leaf-labelling, the topological structure of the trees may display sufficient resemblance so that a higher level consensus could be revealing of evolutionary history. This would be especially true of the peripheral structures of the tree, likely representing events that occurred more recently and have thus been less obscured by subsequent evolutionary processes. Here, we present a statistical test to assess whether the subgenomes in a polyploid genome could have been added one at a time. The null hypothesis is that the accumulation of chromosomes follows a stochastic process in which transition from one generation to the next is through randomly choosing an edge, and then subdividing this edge in order to link the new internal vertex to a new external vertex. We analyze the probability distributions of a number of peripheral tree substructures, namely leaf- or terminal-pairs, triples and quadruples, arising from this stochastic process, in terms of some exact recurrences. We propose some conjectures regarding the asymptotic behaviours of these distributions. Applying our analysis to a sugarcane genome, we demonstrate that it is unlikely that the accumulation of subgenomes has occurred one at a time in this genome.

No description available.

DNA replication is a fundamental process that is primarily regulated at the initiation step. In higher eukaryotes, the location and properties of replication origins are not well understood. Existing genome-wide approaches to map origins—such as nascent strand abundance mapping, Okazaki fragment mapping, or chromatin immunoprecipitation-based assays—average the behavior of a population of cells. However, due to cell-to-cell variability in origin usage, single molecule techniques are necessary to investigate the actual behavior of a cell. Here, I investigate the feasibility of using three single molecule, genome-wide technologies to map origins of replication. The Pacific Biosciences Single Molecule Real-Time (SMRT) sequencing technology, the BioNano Genomics Irys optical mapping technology, and the Oxford Nanopore Technologies MinION nanopore sequencing technology are promising approaches that can advance our understanding of DNA replication in higher eukaryotes.

Saudi Arabia is highly accessible to marine water, receives year-round availability of sunlight and generates a high annual carbon dioxide emission, all of which are justifications that merits the deployment of cyanobacterial cell factories. However, industrial cyanobacterial strains capable of thriving in conditions of the Arabian Peninsula are currently lacking. Given the fact that native cyanobacteria from the Red Sea are adapted to the local conditions, they are therefore good cell factory candidates where their inherent attributes can be harnessed. In this dissertation, an isolation and screening pipeline was developed to specifically identify physiologically robust cyanobacterial strains from the central Red Sea. Seventeen unicellular cyanobacterial strains were extensively cataloged through a series of physiological characterization and their evolutionary relationships were ascertained through phylogenetic analyses. Arising from this survey work, a high light, thermo- and halo-tolerant Synechococcus sp. RSCCF101 was selected for metabolic analysis under various growth conditions to assess its suitability as a platform for cell factory development. Significant metabolic changes were observed in cells subjected to different light regimes. High phycocyanin and chlorophyll a content were obtained under the low-light growth (50 μmol photons.m-2.s-1) while high biomass was accumulated, along with an increase external nitrate demand, under the high light growth (200 μmol photons.m-2.s-1). A genomic and transcriptomic approach was undertaken to elucidate the molecular signatures of Synechococcus sp. RSCCF101. Synechococcus sp. RSCCF101 contains a small genome (3 Mbp) that is rich in guanine cytosine content (68%) and harbors genes that encode for compatible solutes biosynthetic pathway and phycobilisome subunits which may account for its halo-tolerant and phycocyanin rich phenotype. Upon high-light treatment, the light harvesting machineries of Synechococcus sp. RSCCF101 was downregulated while the photosystem protection and carbon fixation capacity were upregulated. Taken together, the findings of this research will facilitate in the development of a new model system for industrial applications in high-light, high temperature and high salinity environments in general and Saudi Arabia in particular.

Analyse intégrative de données génomiques et pharmacologiques pour améliorer la prédiction de la réponse aux thérapies cibléesL'utilisation de thérapies ciblées dans le contexte de la médecine personnalisée du cancer a permis d’améliorer le traitement des patients dans différents types de cancer. Cependant, alors que la décision thérapeutique est basée sur une unique altération moléculaire (par exemple une mutation ou un changement du nombre de copies d’un gène), les tumeurs montrent différents degrés de réponse. Dans cette thèse, nous démontrons que la décision thérapeutique basée sur une unique altération n’est pas optimale et nous proposons un modèle mathématique intégrant des données génomiques et pharmacologiques pour identifier de nouveaux biomarqueurs prédictifs de la réponse thérapeutique. Le modèle a été construit à partir de deux bases de données de lignées cellulaires (the Genomics of Drug Sensitivity in Cancer, GDSC and the Cancer Cell Line Encyclopedia, CCLE) et validé avec des données de lignées et des données cliniques. De plus, nous avons également développé une nouvelle méthode pour améliorer la détection des mutations somatiques à partir de données de séquençage d'exomes complets et proposons un nouvel outil, cmDetect, disponible gratuitement pour la communauté scientifique. / Integrated analysis of genomic and pharmacological data to better predict the response to targeted therapiesThe use of targeted therapies in the context of cancer personalized medicine has shown great improvement of patients’ treatment in different cancer types. However, while the therapeutic decision is based on a single molecular alteration (for example a mutation or a gene copy number change), tumors will show different degrees of response. In this thesis, we demonstrate that a therapeutic decision based on a unique alteration is not optimal and we propose a mathematical model integrating genomic and pharmacological data to identify new single predictive biomarkers as well as combinations of biomarkers of therapy response. The model was trained using two public large-scale cell line data sets (the Genomics of Drug Sensitivity in Cancer, GDSC and the Cancer Cell Line Encyclopedia, CCLE) and validated with cell line and clinical data. Additionally, we also developed a new method for improving the detection of somatic mutations using whole exome sequencing data and propose a new tool, cmDetect, freely available to the scientific community.

Northern Pike (Esox lucius) is an economically and ecologically valuable species with a circumpolar distribution across the Northern Hemisphere. Northern Pike have been shown to have low levels of genetic variation despite their great capacity to colonize new environments. Here, high-resolution resequencing data from 47 Northern Pike from across North America was used for SNP discovery and population analysis. Our analysis reveals an extraordinary lack of genetic variation among Northern Pike with observed heterozygosity (Ho) of just 0.0835. Our analyses suggest that two major groups of Northern Pike exist in North America that are separated by the North American Continental Divide. Genetic variation associated with the stratification of these two groups resides across the genome particularly in gene regions with multiple copy number variants and functions related to immunity, tissue permeability, and development. Northern Pike from Alaska and the Yukon River harbour about two times more heterozygosity than Northern Pike east of the Continental Divide with an average of one heterozygous SNP every 6,250 bases. Populations east of the Continental Divide possess a remarkable level of genetic homogenization with an average of just one heterozygous SNP every 16,500 bases. For comparison, an average of one heterozygous SNP per 309 bases was reported in herring (Martinez Barrio et al., 2016), one per 500 in Atlantic cod (Star et al., 2011), and one per 750 bases in Coho and chinook salmon (Koop, 2018). This is at least 5 – 10 fold less variation than is seen in humans (the 1000 Genomes Project Consortium, 2015). We observed a recently described master sex-determining gene, amhby, in three western North American populations but not in populations east of the Continental Divide. We could not resolve any signals indicating a genetic sex determination system was present in populations from southern Manitoba or the St. Lawrence River. This may indicate that environmental sex determination is at play in these populations. We found evidence of a possible female-heterozygous, male homozygous ZW-ZZ genetic sex-determination system in New Jersey Northern Pike. With the highest average of 181,268 heterozygous SNPs genome wide and the greatest Ho (0.3228) of all populations, as well as the presence of the sex-determining gene amhby indicate that Northern Pike from our Alaskan population are the oldest in North America. Fewer numbers of heterozygous SNPs (61,073), low Ho (0.0922), and the absence of amhby in Northern Pike east of the Continental Divide suggests that these are relatively young populations and are descended from a small founding population. These results imply that Northern Pike first came to North America through Beringia and colonized its North American range from there, possibly via pro-glacial lake formation and drainage. However, from the data herein it was not possible to trace how re-colonization occurred after the final retreat of glaciers at the end of the last ice age. This thesis provides a genetically high-resolution snapshot of Northern Pike population structure in North America. It demonstrates that organisms with largely homogenous genomes can be incredibly successful and resilient. Finally, it adds to the complex subject of sex determination in fish and provides insight into a sex determination system in transition. / Graduate / 2020-10-15

Anglerfishes are easily one of the most popular deep-sea creatures due to their menacing appearance, extreme sexual dimorphism, parasitic mating approach, and eye catching bioluminescent lure. Unlike most bioluminescent fishes, which intrinsically generate light, female anglerfishes belonging to nine of the 11 families within the suborder Ceratioidei (deep-sea anglerfishes) have developed a symbiotic relationship with bioluminescent bacteria that are housed within the light organs. Previous molecular work had identified symbionts from two anglerfish species as novel and possibly unculturable taxa (Haygood et al., 1992), but nothing more has been revealed about the bioluminecent symbionts of ceratioids. As part of the Gulf of Mexico Research Initiative-funded DEEPEND project (Deependconsortium.org), the objective of this study is to characterize the escal microbiome of deep-sea anglerfishes and identify potential-symbiont taxa. A total of 36 anglerfish specimens were collected on DEEPEND cruises DP01 through DP04. These specimens consist of adult and larval individuals belonging to six of the families with the suborder Ceratioidei: Ceratiidae (n=22), Oneirodidae (n=7), Linophrynidae (n=3), Melanocetidae (n=2), Centrophrynidae (n=1), Melanocetidae (n=2), Gigantactinidae (n=1). DNA was extracted from esca, skin, fin, gill, gut, and caruncle tissues, as well as seawater. High-throughput sequencing of the 16S rRNA hypervariable V4 region was carried out using the Illumina MiSeq. Sequencing revealed five potential bioluminescent-symbiont taxa (OTU IDs: 9129, 9131, 160210, 523223, and 939811), which had the greatest relative abundance (25.2% - 98.7%) within 12 of 21 adult specimens. These taxa belong to the family Vibrionaceae and were found at greater than 10% relative abundance in the escal samples of adult anglerfishes belonging to the Ceratiidae and Melanocetidae families, but they were not found in high abundance in larval individuals of the same families. Sequencing of larval samples revealed five potential bioluminescent-symbiont taxa (OTU IDs: 136178, 176420, 523223, 837366, 939811) which were of greatest relative abundance (8.1%-67.1%) within nine of 13 specimens. Also members of the family Vibrionaceae, these taxa were found in high abundance in larval anglerfishes belonging to the Oneirodidae, Linophrynidae, Gigantactinidae, and Ceratiidae families. This study is the first to to examine the bioluminescent symbionts from seven different ceratioid families.