Mammalian recombination hot spots: properties, control and evolution

Abstract

Recombination, together with mutation, generates the raw material of evolution, is essential for reproduction and lies at the heart of all genetic analysis. Recent advances in our ability to construct genome-scale, high-resolution recombination maps and new molecular techniques for analysing recombination products have substantially furthered our understanding of this important biological phenomenon in humans and mice: from describing the properties of recombination hot spots in male and female meiosis to the recombination landscape along chromosomes. This progress has been accompanied by the identification of trans-acting systems that regulate the location and relative activity of individual hot spots.

Figure 1. Hot spot positioning and intensity

a | Recombination rate variation along human chromosome 12. The graph shows the recombination rate estimated from a genome-wide survey of genetic variation (black bars) and estimated recombination rates from the deCODE genetic map (red line). Recombination hot spots are evident as black spikes surrounded by regions of low or no recombination. Underneath the graph is a cytological banding map of the chromosome. Note the lack of recombination activity near the centromere (purple), b | Estimated locations and intensities of several hot spots in the human major histocompatibility complex (MHC) region inferred by coalescent-based statistical methods (left panel, human leukocyte antigen (HLA)-DMA; right panel, HLA-DMB). Positions along the x-axis are in base pairs according to the consensus map of the human MHC The green lines show estimates from the coalescent method, and the vertical black lines and dashed grey lines show the approximate hot spot centre and the approximate hot spot boundaries, respectively, as estimated from sperm-typing results. Part a is modified, with permission, from REF. 24 © (2005) American Association for the Advancement of Science. Part b is reproduced, with permission, from Nature Genetics REF. 22

Figure 2. High-resolution sex-specific maps of a mouse chromosome segment

The plot shows the recombination map of a 27-Mb telomeric region of mouse chromosome 1 in a cross between C57BL/6J and CAST/EiJ strains, highlighting the difference in the recombination rate between the two sexes. The F₁ hybrids were either female or male and derived from reciprocal parental combinations (a total of 6,000 progeny). The width of each vertical line indicates the resolution attained. Female recombination rates are in red and male recombination rates are in blue. The arrows show sex-specific hot spots.

Figure 3. Distribution of crossover exchange points in hot spots

a | Sperm crossover (CO) distribution across the NID1 hot spot. The COs were recovered from a total of 980,000 amplifiable molecules in the sperm DNA of two men. The intervals are defined by SNP markers, and the number of COs is shown above each interval. Exchange sites of crossing over form a single normal distribution, b | Distribution of COs at the Hlx1 hot spot in 6,000 progeny of female and male B6×CAST F₁ mouse hybrids. The number of COs in female (red) and male (blue) meiosis is shown above each interval. Exchange sites of crossing over form two overlapping distributions. Part a is modified, with permission, from Nature Genetics REF. 18 © (2005) Macmillan Publishers Ltd. All rights reserved. Part b is modified from REF .