Date of Degree
PhD (Doctor of Philosophy)
Comeron, Josep M.
First Committee Member
Second Committee Member
Third Committee Member
Fourth Committee Member
The study of natural variation is a principle component of biology. One process that affects levels of natural variation is meiotic recombination—the process by which homologous chromosomes break and interchange genetic information with one another during the formation of gametes. Surprisingly, this factor that shapes levels of natural variation across the genome itself presents with a great deal of variation. That variation manifests itself at many levels: within genomes, between individual organisms, across populations, and among species. The factors and mechanisms responsible for the non-random patterning of recombination events across the genome remain particularly elusive in most cases. Herein, I utilize a combination of bioinformatic and molecular genetic approaches to better explain recombination patterning. I explore several factors that are now known to contribute to the distribution of recombination events across genomes. In particular, I demonstrate that transcriptional activity during meiosis is associated with, and partially predictive of crossing over events in Drosophila melanogaster. Additionally, I present a model which is capable of accounting for approximately 40% of the variation in crossover rates in Drosophila based on the localization of several previously identified DNA motifs. Lastly, I present preliminary data describing how recombination patterns are altered under naturally stressful conditions, a key insight that is necessary for uniting our findings at one level of variation with the many others. These findings support a multifactorial model for crossover distribution that includes both genetic and epigenetic factors and will further progress the field in developing a comprehensive understanding of recombination localization.
Meiotic recombination, the process by which parental chromosomes are broken and repaired to generate a patchwork of genetic material, maintains genetic diversity by allowing individual sites in the DNA to take on separate evolutionary trajectories. This process of forming and repairing breaks in double-stranded DNA, occurs non-randomly across the genome. The reasons for the non-random distribution of breaks and the factors that affect it are poorly understood in all organisms examined. Because recombination shapes levels of genetic diversity, it is important to understand how and why recombination is varied in order to draw conclusions about the evolution of a species and in order to assist in the association between many diseases and their causative genetic mutations.
The work presented in this thesis is an investigation of recombination rate variation in a fruit fly model and the factors that affect its genomic distribution. In particular, I present a study of meiotic gene expression and how recombination rates are affected by genes that are ‘on’ during the formation of double-stranded breaks in the DNA. I also present a study of DNA motifs and how these motifs may be predictive of recombination rate variation. Lastly, I examine how recombination rates are altered under stressful conditions to better understand how the many levels of recombination variation are intertwined. My findings demonstrate that many factors—both genetic and epigenetic—are involved in shaping variation in recombination rates, and a combination of each can account for a large proportion of the variation we observe within genomes.
Crossing over, DNA, DSB, Linkage, Polymorphism, Transcription
xi, 128 pages
Copyright © 2015 Andrew Blake Adrian
Adrian, Andrew B.. "Fine scale recombination variation in Drosophila melanogaster." PhD (Doctor of Philosophy) thesis, University of Iowa, 2015.