Molecular origin and fate of segmental duplications in the Saccharomyces cerevisiae genome.
Romain Koszul, Bernard Dujon, Gilles Fischer
Génétique Mol. des Levures, Institut Pasteur, 25 rue du Dr Roux, PARIS, 75724, FRANCE
The high level of gene redundancy found in all eukaryotic genomes sequenced so far revealed a major role for DNA duplication in genome evolution. We have recently demonstrated experimentally that large DNA segments, covering tens to hundreds of kilobases, can be spontaneously duplicated in the Saccharomyces cerevisiae genome. Most of these events were intrachromosomal but some interchromosomal duplications were also characterized. Three categories of recombining sequences were found at the breakpoints: transposon-related sequences, microsatellites and micro-homologous sequences. The same experiment ran in various mutant backgrounds shows that the mechanism leading to the formation of segmental duplications is independent from homologous recombination between repeated sequences. Furthermore, a replication timing defect increases 100 times the frequency of duplication, demonstrating the existence of a molecular mechanism that would be related to replication and different from unequal crossing-over. In addition, the stability of the different kind of duplicated blocks, freed from any selective pressure, was tested. Direct tandem duplicated segments are lost at relatively high frequency, whereas interchromosomal duplications appear to be strongly stabilized within the genome. The importance of segmental duplications in evolution will be discussed, in the light of the recent complete genome sequences from various hemiascomycete yeast species.
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