Understanding the heterogeneity in meiotic recombination rates is imperative, in light of its multifaceted role in affecting adaptive evolution and shaping genetic diversity within a population. This work is focused on studying the fine-scale (a resolution of a few kilobasepairs) variation in meiotic recombination rates in Caenorhabditis elegans in an effort to understand the mechanistic and evolutionary forces shaping the genetic diversity in this organism.;The C. elegans chromosomes (five autosomes and an X chromosome) show a reproducible pattern of low recombination in the center of the chromosome versus high recombination in the chromosome arms, distinguished by pronounced boundary regions. The causes underlying this distinct domain structure are unknown. Using C. elegans strains with a wild-type chromosomal complement for targeted genetic crosses in conjunction with dense molecular genotyping, a high-resolution recombination rate map of the chromosome 2 center-right arm recombination rate boundary region was generated. The wildtype distribution of crossovers in this 2.275 Mb region is characterized by well-defined large-scale domains with limited fine-scale rate heterogeneity. In fact, using the Gini coefficient as a summary statistic we found that this region had the least heterogeneous fine-scale distribution among the model organisms with comparable crossover distribution data available, and that our data for this region was incompatible with a mammalian-type hotspot-rich recombination landscape. The large-scale domains of recombination rate variation in this region are separated by a discrete boundary, which we localize to a small region. Our comparison of this high-resolution recombination rate map to the currently known distributions of genomic features in the C. elegans genome showed that the recombination rate boundary coincided with the arm-center boundary defined both by nuclear-envelope attachment of DNA in somatic cells and GC content. These observations are consistent with proposals that these features of chromosomal organization may be mechanical causes and evolutionary consequences of meiotic recombination.;To explore the individual contributions of local sequence features and the chromosome-wide recombination rate domain structure in dictating the crossover distribution in this region we measured the fine-scale recombination rate variation in alternative chromosomal context using whole chromosome fusion strains. We show that both sequence features and chromosomal context shape the fine-scale crossover distribution in this region. We observed that the crossover distributions measured in the contrasting chromosomal context were strikingly conserved, indicating the role of sequence in shaping this rate heterogeneity. Our comparison of the fusion and wildtype karyotype fine-scale crossover distributions along with the chromosome-wide crossover distributions allow us to uncouple the role of sequence and chromosome-wide domain structure in shaping the pattern of crossover distribution in this region of the C. elegans genome.;In order to understand the pattern of linkage disequilibrium, a reliable readout of natural selection, mutation, gene conversion, population structure and level of outcrossing in a population, knowledge of the recombination rate variation in the genomic region is crucial. The high-resolution empirical measures of recombination rates from this study make possible future investigations to explicitly test theoretical predictions of the relationship between linkage disequilibrium and recombination rate variation in C. elegans.
展开▼