Macrotene chromosomes provide insights to a new mechanism of high-order gene amplification in eukaryotes

Agnès Thierry, Varun Khanna, Sophie Créno, Ingrid Lafontaine, Laurence Ma, Christiane Bouchier and Bernard Dujon ()
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Agnès Thierry: Institut Pasteur, Unité de Génétique moléculaire des levures, CNRS UMR3525, Sorbonne Universités, UPMC, Univ. Paris 06 UFR927, 25, rue du Docteur Roux
Varun Khanna: Institut Pasteur, Unité de Génétique moléculaire des levures, CNRS UMR3525, Sorbonne Universités, UPMC, Univ. Paris 06 UFR927, 25, rue du Docteur Roux
Sophie Créno: Institut Pasteur, Genomic platform, 28, rue du Docteur Roux
Ingrid Lafontaine: Institut Pasteur, Unité de Génétique moléculaire des levures, CNRS UMR3525, Sorbonne Universités, UPMC, Univ. Paris 06 UFR927, 25, rue du Docteur Roux
Laurence Ma: Institut Pasteur, Genomic platform, 28, rue du Docteur Roux
Christiane Bouchier: Institut Pasteur, Genomic platform, 28, rue du Docteur Roux
Bernard Dujon: Institut Pasteur, Unité de Génétique moléculaire des levures, CNRS UMR3525, Sorbonne Universités, UPMC, Univ. Paris 06 UFR927, 25, rue du Docteur Roux

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: Abstract Copy number variation of chromosomal segments is now recognized as a major source of genetic polymorphism within natural populations of eukaryotes, as well as a possible cause of genetic diseases in humans, including cancer, but its molecular bases remain incompletely understood. In the baker’s yeast Saccharomyces cerevisiae, a variety of low-order amplifications (segmental duplications) were observed after adaptation to limiting environmental conditions or recovery from gene dosage imbalance, and interpreted in terms of replication-based mechanisms associated or not with homologous recombination. Here we show the emergence of novel high-order amplification structures, with corresponding overexpression of embedded genes, during evolution under favourable growth conditions of severely unfit yeast cells bearing genetically disabled genomes. Such events form massively extended chromosomes, which we propose to call macrotene, whose characteristics suggest the products of intrachromosomal rolling-circle type of replication structures, probably initiated by increased accidental template switches under important cellular stress conditions.

Date: 2015
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DOI: 10.1038/ncomms7154

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