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. 2008 Jul 11;4(7):e1000119.
doi: 10.1371/journal.pgen.1000119.

The Recombinational Anatomy of a Mouse Chromosome

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Free PMC article

The Recombinational Anatomy of a Mouse Chromosome

Kenneth Paigen et al. PLoS Genet. .
Free PMC article

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 1.2x 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.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Recombination map of Chr 1.
A. Sex-averaged recombination map of Chr 1 in C57BL/6J×CAST/EiJ cross. Boxes represent runs of consecutive intervals showing recombination (red) or no recombination (blue). B. Cytological map of Chr 1 (from ENSEMBL). C. Correlation between recombination rates in C57BL/6J×CAST/EiJ backcross and HS mice at different resolution. The red line represents the best fitting logarithmic trend extrapolated to zero correlation. The best fitting function and its correlation coefficient are shown, indicating that correlation between the two crosses approaches zero at distances around 0.05 Mb.
Figure 2
Figure 2. Distribution of recombination rates on Chr 1.
A. Distribution of recombination in intervals of increasing rates (intervals lacking recombination are not included). The rates are presented in logarithmic scale to emphasize the exponential shape of the distribution. The deviation at the lower end of the distribution represents low-activity intervals mapped to a lower resolution. Red line represents the best fitting exponential function. The exponential function and its correlation coefficient are shown. B. Cumulative recombination as a function of chromosomal size. Both recombination rates and chromosomal length are expressed as fractions of the total. The intervals are in rank order of increasing recombination rate.
Figure 3
Figure 3. Fine mapping of recombination activities.
A. Sex-averaged map of the region of 168.8–193.5 on Chr 1. Recombination rates in intervals that are off scale are shown as numbers over each interval. The red circles mark newly identified hotspots; full circles, hotspots that were sequenced through to determine the fine positioning of crossover exchanges. B. Hotspots in the third intron of Esrrg (189.75–189.8 Mb). C. Number of intervals containing recombination activity higher than given thresholds at different interval size. The threshold levels are shown in the legend.
Figure 4
Figure 4. Sex specificity of recombination.
A. Sex-specific recombination map of Chr 1. Red line, female recombination rates; blue line, male recombination rates. B. Female:male ratio along the chromosome. Dark blue line: female:male ratio; purple line: sex-averaged recombination rate over the entire Chr 1.
Figure 5
Figure 5. High-resolution sex-specific recombination maps of the interval between 168.8–193.5 Mb.
Recombination rates in intervals that are off scale are shown as numbers over each interval. Red arrows: hotspots predominantly active in females; blue arrows: hotspots predominantly active in males.
Figure 6
Figure 6. Distribution of crossover exchange points at hotspot 186.3.
A. Physical positions of the SNPs used to determine the crossover exchange points according to NCBI Build 36. In panels B, C and D, the left end (0) corresponds to 186,316,643 A/G. B. Distribution of crossover exchange points in female and male progeny. The number of crossovers in each interval is shown. Red, females; blue, males. C. Distribution of reciprocal crossovers (B-C and C-B) in female progeny. The number of crossovers in each interval is shown. Red, B-C; tan, C-B. D. Distribution of reciprocal crossovers (B-C and C-B) in male progeny. The number of crossovers in each interval is shown. Blue, B-C; green, C-B.

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