engleski

Ends-out recombination as a source of genetic duplications in Yeast

Systematic whole-genome studies in diverse organisms emphasize the role of duplications of genetic material in evolution of the living world. However, the mechanisms underlying gene, segment, chromosome and genome duplications are still largely unknown. We studied yeast transformation with linear DNA molecules as a model for the study of genetic recombination. Yeast Saccharomycs cerevisiae is known to incorporate foreign DNA almost exclusively by homologous recombination, either during targeted plasmid integration (“ ends-in” recombination) or during one-step gene replacement (“ ends-out” recombination). However, we found out that gene replacement may be accompanied by different “ aberrant” recombination events. Detailed molecular analysis of such transformants indicated frequent illegitimate integrations of the transforming fragment, but also integrations to homology preceded by ligation of the free DNA ends. Such complex events, known as homology-associated illegitimate recombination (HAIR) give rise to tandem duplications in the genome. We also identified duplications of the target chromosome suggesting that aneuploidy may be another genetic endpoint of the transformation process. Based on these results we present a model that relates ends-out recombination not only to the generation of dispersed and tandem gene/segment repeats, but also to duplications of entire chromosomes.

gene targeting; gene duplication; aneuploidy; homologous recombination; illegitimate recombination

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