Browsing by Author "Omer, Arina D."
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Item Chromosome size affects sequence divergence between species through the interplay of recombination and selection(Wiley, 2022) Tigano, Anna; Khan, Ruqayya; Omer, Arina D.; Weisz, David; Dudchenko, Olga; Multani, Asha S.; Pathak, Sen; Behringer, Richard R.; Aiden, Erez L.; Fisher, Heidi; MacManes, Matthew D.; Center for Theoretical and Biological PhysicsThe structure of the genome shapes the distribution of genetic diversity and sequence divergence. To investigate how the relationship between chromosome size and recombination rate affects sequence divergence between species, we combined empirical analyses and evolutionary simulations. We estimated pairwise sequence divergence among 15 species from three different mammalian clades—Peromyscus rodents, Mus mice, and great apes—from chromosome-level genome assemblies. We found a strong significant negative correlation between chromosome size and sequence divergence in all species comparisons within the Peromyscus and great apes clades but not the Mus clade, suggesting that the dramatic chromosomal rearrangements among Mus species may have masked the ancestral genomic landscape of divergence in many comparisons. Our evolutionary simulations showed that the main factor determining differences in divergence among chromosomes of different sizes is the interplay of recombination rate and selection, with greater variation in larger populations than in smaller ones. In ancestral populations, shorter chromosomes harbor greater nucleotide diversity. As ancestral populations diverge, diversity present at the onset of the split contributes to greater sequence divergence in shorter chromosomes among daughter species. The combination of empirical data and evolutionary simulations revealed that chromosomal rearrangements, demography, and divergence times may also affect the relationship between chromosome size and divergence, thus deepening our understanding of the role of genome structure in the evolution of species divergence.Item Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation(Elsevier, 2019) Senigl, Filip; Maman, Yaakov; Dinesh, Ravi K.; Alinikula, Jukka; Seth, Rashu B.; Pecnova, Lubomira; Omer, Arina D.; Rao, Suhas S. P.; Weisz, David; Buerstedde, Jean-Marie; Aiden, Erez Lieberman; Casellas, Rafael; Hejnar, Jiri; Schatz, David G.; Center for Theoretical Biological PhysicsSomatic hypermutation (SHM) introduces point mutations into immunoglobulin (Ig) genes but also causes mutations in other parts of the genome. We have used lentiviral SHM reporter vectors to identify regions of the genome that are susceptible (“hot”) and resistant (“cold”) to SHM, revealing that SHM susceptibility and resistance are often properties of entire topologically associated domains (TADs). Comparison of hot and cold TADs reveals that while levels of transcription are equivalent, hot TADs are enriched for the cohesin loader NIPBL, super-enhancers, markers of paused/stalled RNA polymerase 2, and multiple important B cell transcription factors. We demonstrate that at least some hot TADs contain enhancers that possess SHM targeting activity and that insertion of a strong Ig SHM-targeting element into a cold TAD renders it hot. Our findings lead to a model for SHM susceptibility involving the cooperative action of cis-acting SHM targeting elements and the dynamic and architectural properties of TADs.