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WHERE THE CROSSOVERS ARE: RECOMBINATION DISTRIBUTIONS IN MAMMALS
Liisa Kauppi*,Alec J. Jeffreys* and Scott Keeney
Until recently, recombination studies in humans and mice had identified only a few anecdotal examples of crossover hot spots. Recently, the pace of discovery has accelerated. In every genomic segment that has been examined at sufficiently high resolution, recombination events have a punctate recombination distribution: they are clustered within small (12-kb) regions that are surrounded by large stretches of recombinationally suppressed DNA. Here, we review progress in understanding the distribution of mammalian recombination events, tie mammalian results together with informative studies in budding yeast and discuss the consequences of these findings for genome diversity and evolution.
In most sexually reproducing organisms, crossover recombination events provide physical connections between homologous chromosomes. These connections work in conjunction with sister-chromatid cohesion to ensure proper chromosome segregation during the first meiotic division1,2.The formation of crossovers also has the effect of breaking up HAPLOTYPES,therefore
increasing genetic diversity from one generation to the next. Because of this effect, meiotic recombination exerts a profound influence on genome diversity and evolution. Studies in many organisms demonstrate that recombination events are more likely to occur in some parts of the genome than in others. Understanding this nonrandom distribution has important implications for explaining genome plasticity and for our ability to map disease-related loci.
In the past few years, our understanding of the distribution of recombination events in humans has drastically changed. Recent studies strongly support the view that most recombination events occur at highly localized hot spots, whereas the bulk of the DNA is cold. In this review, we discuss low-resolution experiments that first documented the existence of recombination hot spots in humans and mice, and review more recent high-resolution studies that reveal the highly localized clustering of recombination events. Because the emerging
pattern in mammals seems similar to that documented in budding yeast (Saccharomyces cerevisiae), we review molecular details in this model organism that are informative for understanding the mechanisms that dictate recombination distributions in mammals. We then discuss the implications that this highly punctuated recombination distribution has for understanding genome architecture.
Several experimental approaches have been used to characterize the frequency and spatial distribution of meiotic recombination events. All show that recombination in mammals is nonrandomly...