Comparisons among model organisms make clear that, despite the fundamental importance of recombination in sexually-reproducing species, the mechanisms by which it is directed to the genome can vary markedly. Notably, in mice and humans, recombination almost exclusively occurs where the protein PRDM9 binds DNA. In such species, fine-scale recombination rates along the genome are rapidly evolving, as shifts in PRDM9 binding affinity remodel the landscape. In other species such as birds or canids, PRDM9 has been lost and recombination occurs preferentially at promoter-like features, leading to the conservation of recombination rates over large evolutionary distances. Increased recombination near promoters is also seen in human and mouse knockouts for PRDM9, indicating that this mechanism is normally out-competed by PRDM9 binding. The rapid evolution of complete orthologs of PRDM9 in non-mammalian vertebrates suggests that the protein may play a similar role in directing recombination outside of mammals.
In chapter 2 of this work, we test this hypothesis by focusing on the corn snake Pantherophis guttatus, a representative vertebrate species with a single, complete PRDM9 ortholog that is rapidly evolving. We improved the assembly and annotation of the corn snake reference genome and resequenced 24 unrelated corn snake samples to high coverage in order to infer historical recombination rates across the genome from patterns of linkage disequilibrium. We find evidence for elevated recombination around computationally predicted PRDM9 binding sites but, surprisingly, also near promoter features. To verify these findings, we resequenced two pedigrees, identified the PRDM9 alleles segregating in the families and called crossover events that occurred in the parents.
This analysis confirmed that crossover events overlap both PRDM9 binding sites and promoter features more than expected by chance. Thus, unlike in mammalian species that rely on PRDM9, in corn snakes there appears to be a mixed use of PRDM9 binding sites and promoter like features, and we find evidence that the relative importance of these features differs between macro- and microchomosomes. We hypothesize that the dual usage of these features reflects a tug of war between PRDM9 and promoter features, whose strength in snakes and possibly other vertebrates has been shifted by changes to a gene that reads the histone modifications made by PRDM9, and likely other genes. In chapter 3, I discuss how follow-up experiments based on these observations could help answer long-standing questions related to the conditions under which PRDM9-directed recombination localization is favorable. Beyond the specific results, this work illustrates how the study of non-model organisms can inform our understanding of basic genetic mechanisms.
| Identifer | oai:union.ndltd.org:columbia.edu/oai:academiccommons.columbia.edu:10.7916/3bn3-ej41 |
| Date | January 2024 |
| Creators | Hoge, Carla R. |
| Source Sets | Columbia University |
| Language | English |
| Detected Language | English |
| Type | Theses |
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