Abstract
Among mammals, genetic recombination occurs at highly delimited sites known as recombination hotspots. They are typically 1–2 kb long and vary as much as a 1,000-fold or more in recombination activity. Although much is known about the molecular details of the recombination process itself, the factors determining the location and relative activity of hotspots are poorly understood. To further our understanding, we have collected and mapped the locations of 5,472 crossover events along mouse Chromosome 1 arising in 6,028 meioses of male and female reciprocal F1 hybrids of C57BL/6J and CAST/EiJ mice. Crossovers were mapped to a minimum resolution of 225 kb, and those in the telomere-proximal 24.7 Mb were further mapped to resolve individual hotspots. Recombination rates were evolutionarily conserved on a regional scale, but not at the local level. There was a clear negative-exponential relationship between the relative activity and abundance of hotspot activity classes, such that a small number of the most active hotspots account for the majority of recombination. Females had 1.2× higher overall recombination than males did, although the sex ratio showed considerable regional variation. Locally, entirely sex-specific hotspots were rare. The initiation of recombination at the most active hotspot was regulated independently on the two parental chromatids, and analysis of reciprocal crosses indicated that parental imprinting has subtle effects on recombination rates. It appears that the regulation of mammalian recombination is a complex, dynamic process involving multiple factors reflecting species, sex, individual variation within species, and the properties of individual hotspots.
Highlights
Genetic recombination is a fundamental process common to all eukaryotic organisms, which ensures proper chromosomal segregation of homologous chromosomes in meiosis and increases genetic diversity by creating new combinations of parental alleles at each generation
According to the most widely accepted model of double-strand break processing [1], crossovers are predominantly produced by double-strand break repair (DSBR), and non-crossovers are predominantly produced by synthesisdependent strand annealing (SDSA) [2]
Hotspots are not believed to be present in organisms such as Drosophila and C. elegans where synapsis precedes recombination [6,7], local variation of recombination rates across large genomic regions exists in these organisms [8,9]
Summary
Genetic recombination is a fundamental process common to all eukaryotic organisms, which ensures proper chromosomal segregation of homologous chromosomes in meiosis and increases genetic diversity by creating new combinations of parental alleles at each generation. The resected regions are eventually repaired using the non-sister chromatid as a template, producing two types of recombination products: crossovers, and gene conversions without exchange of flanking markers (non-crossovers). The majority of recombination is localized to very limited intervals along the genome, termed hotspots, which in mammals are typically only 1-2 kilobase pairs (kb) long [3] and are surrounded by much longer regions (tens of kilobases or more) lacking recombination. Hotspots are not believed to be present in organisms such as Drosophila and C. elegans where synapsis precedes recombination [6,7], local variation of recombination rates across large genomic regions exists in these organisms [8,9]
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