Local Rates of Recombination Are Positively Correlated with GC Content in the Human Genome

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Abstract
The GC content of human DNA varies widely across the genome, ranging from 30% to 60%, and regions of hundreds of kilobases (often referred to as isochores [Bernardi 2000]) may have relatively homogeneous base compositions. This compositional heterogeneity appears to be very widespread in eukaryotes (Nekrutenko and Li 2000) and may represent an important level of genome organization, insofar as gene density (Zouback, Clay, and Bernardi 1996 ), gene length (Duret, Mouchiroud, and Gautier 1995 ), and patterns of codon usage (Sharp et al. 1995 ), as well as the distribution of different classes of repetitive elements (Soriano, Meunier-Rotival, and Bernardi 1983 ; Duret, Mouchiroud, and Gautier 1995 ), are all correlated with GC content. Despite intensive investigation, the underlying cause(s) of the observed heterogeneity remains contested, with two major hypotheses competing: Bernardi has suggested that selection is primarily responsible for maintaining the observed patterns (Bernardi and Bernardi 1986 ; Bernardi 2000 ), a view supported by recent analysis of polymorphism in the human MHC cluster (Eyre-Walker 1999 ), whereas the balance of opinion has favored systematic mutational bias as the ultimate cause (Filipski 1987 ; Suoeka 1988; Wolfe, Sharp, and Li 1989 ; Francino and Ochman 1999 ). Ultimately, however, it is not clear why either selection for increased GC content or mutation bias should promote such marked local variation in genomic nucleotide content.