The Recombinational Anatomy of a Mouse Chromosome

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.

Scrambling Eggs: Meiotic Drive and the Evolution of Female Recombination Rates

“…This pattern has been noted in fish (Sakamoto et al 2000;, humans (Broman et al 1998;Clark et al 2010), dogs (Wong et al 2010), and mice Paigen et al 2008), although there are some exceptions [e.g., opossums (Samollow et al , 2007]. Utilizing data from a recent fine-scale analysis of sex-specific recombination rate in humans (Kong et al 2010), we display an example of this pattern in Figure 1B.…”

Evolution of the Genomic Recombination Rate in Murid Rodents

“…Because reciprocal F 1 's are genetically identical, barring the parental origin of their sex chromosomes and mitochondria, these findings provide preliminary evidence for sex-linked and/or mitochondrial factors contributing to subspecies polymorphism in recombination rate. However, we cannot rule out the possibility that these patterns are influenced by imprinting or maternal effects (Paigen et al 2008;Ng et al 2009), especially given that our analysis is limited to males.…”

Recombination rate variation in closely related species

“…In comparing the same intervals between two closely related species in the absence of a genome sequence, one runs the risk of concluding increased divergence between species when in actuality, an inversion, insertion or deletion segregating in only one species is obscuring their comparable recombination rates. Third, recombination is variable within individuals and populations (Brooks and Marks, 1986;True et al, 1996;Carrington and Cullen, 2004;Neumann and Jeffreys, 2006;Graffelman et al, 2007;Coop et al, 2008;Paigen et al, 2008;Cheng et al, 2009;Dumont et al, 2009;Kong et al, 2010 etc). This variation may stem from actual heritable variation in recombination rates among individuals; variation within an individual among regions of its genome (as discussed above) or from environmental variation.…”