Recombination is proportional to the number of chromosome arms in mammals.

In sexually reproducing organisms recombination contributes significantly to the processes of DNA repair, fidelity of chromosome segregation, and generation of genetic diversity. Abnormal recombination is associated with decreased fitness of offspring, aneuploidy, and several human diseases (Chaganti et al. 1974; Charlesworth and Barton 1996; Hassold et al. 2000). Despite its importance, little is known of how the rate and pattern of recombination is regulated in higher eukaryotes, although sex, DNA sequence, chromatin structure, chromosomal location, and chromosome size have been shown to influence the recombination rate (Robinson 1996). Mammals show great interspecific variability of recombination rate. For example, the level of recombination in human is more than twice that observed in the mouse. Neither the total DNA content nor the diploid number of chromosomes account for these differences. The DNA content of the mammalian genome is fairly constant and, on average, the haploid genome consists of 3.0 × 10 bp (Sober 1968). Studies in Drosophila and other organisms indicate that proper chromosome segregation generally requires at least one recombination event per chromosome (Mather 1936). Because crossing-over is associated with proper distributive segregation of each bivalent at the first meiotic division, the diploid number of chromosomes establishes the minimum number of recombination events that occurs per meiosis. However, this parameter correlates poorly with the observed recombination frequency in mammals (Burt and Bell 1987). In an under-appreciated report, Dutrillaux (1986) demonstrated empirically that there is a strong correlation between number of chiasma (NC) and the haploid number of chromosome arms. Although he did not provide the correlation statistics for his regression analysis, the variance explained is very high (R 4 0.90; F < 1.32 × 10; b in Fig. 1a). Dutrillaux concluded that NC is proportional to the haploid number of chromosome arms (NF/2) of the karyotype, where NF is the “fundamental number” (Matthey 1945). This result was in agreement with a cytological study that indicated the occurrence of an obligatory chiasmata in each chromosomal arm in human males (Hulten 1974). In the intervening years, genome-wide recombination studies have permitted the establishment of linkage maps of several mammalian species (see below) and provided important information about the process of meiotic non-disjunction, the major cause of aneuploidy (Hassold et al. 2000). In addition, recombination still remains at the center of one of the most vexing problems in evolutionary biology, sex. Burt and Bell (1987) used mammalian chiasma frequencies as a test of two competing hypotheses to explain the selective force resulting in sex and recombination; the Red Queen and the Tangled Bank (Maynard Smith 1978; Bell 1982; Charlesworth 1985). The Red Queen hypothesis proposes that recombination is selected to counter the antagonistic advances made by the biotic environment, particularly parasites, during the previous generations. This hypothesis predicts that recombination is positively correlated with age to maturity, because the longer the time between generations, the more contrary will be the environment and the more intense the selection (Bell 1982). Burt and Bell (1987) demonstrated that the number of chiasma in excess of one per bivalent (“excess of chiasma” or EC) was strongly correlated with age to maturity. However, the number of chromosome arms was not among the parameters tested (haploid number, age to maturity, litter size, and adult body weight) for correlation with EC in this study. We have performed a regression analysis, using 21 of the 24 nondomesticated mammalian species reported by Burt and Bell (1987) for which the karyotypes are available to us. We find that, in agreement with the expectations of Dutrillaux, there is a very strong correlation (R 4 0.79; F < 7.16 × 10; a in Fig. 1a) between NC and the haploid number of chromosome arms (FN/2). The small differences between the two regression lines (NC 4 0.84(N/2) + 5.1 and NC 4 0.85(NF/2) + 7.3; a and b respectively in Fig. 1a) can be ascribed to intra-specific variability, methodological differences, and/or sampling errors. Another estimate of the genome-wide recombination rate in a species is the total length of the linkage map. Linkage maps have been reported for 11 mammalian species. The species for which linkage maps are available may be divided into two groups based on the number of independent maps, map coverage and density, and the number of informative meioses analyzed. In the first group, we include species with more than one reported map, extensive genome coverage, and moderate to high marker density. This group includes human, mouse, pig, dog, rat, and cattle (Serikawa et al. 1992; Barendse et al. 1994; Ellegren et al. 1994; Archibald et al. 1995; Dib et al. 1996; Dietrich et al. 1996, Ma el al. 1996; Rohrer et al. 1996; Bihoreau et al. 1997; Kappes et al. 1997; Andoh et al. 1998; Broman et al. 1998; Rhodes et al. 1998; Szpirer et al. 1998; Neff et al. 1999; Paszek et al. 1999; Steen et al. 1999, Werner et al. 1999; Kitada et al. 2000; McCarthy et al. 2000; Mellersh et al. 2000; Mouse Genome Informatics, http:// www.informatics.jax.org September 2000). As observed for NC, the size of the linkage map is strongly correlated with the haploid number of chromosome arms (FN/2) (R 4 0.81; F < 0.014; Fig. 1b). In Figure 1b, we have also included five species (cat, goat, sheep, horse and baboon, plotted as open circles) for which linkage maps are deficient in one or more of the criteria mentioned above (Crawford et al. 1995; Vaiman et al. 1996; Lindgren et al. 1998; Schibler et al. 1998; Menotti-Raymond et al. 1999; Kiguwa et al. 2000; Rogers et al. 2000; Swinburne et al. 2000). Although these Correspondence to: C. Sapienza; E-mail: sapienza@unix.temple.edu