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

Agnès Thierry (1) , Varun Khanna (1) , Sophie Créno (2) , Ingrid Lafontaine (1) , Laurence Ma (2) , Christiane Bouchier (2) , Bernard Dujon (1)

1 Génétique Moléculaire des Levures
2 Génomique (Plate-Forme) - Genomics Platform

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 chromo-somes, 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.

Mots clés: Molecular biology; Genetics; Biological sciences

Domaines: Génétique; Microbiologie et Parasitologie

Agnès Thierry, Varun Khanna, Sophie Créno, Ingrid Lafontaine, Laurence Ma, et al.. Macrotene chromosomes provide insights to a new mechanism of high-order gene amplification in eukaryotes. Nature Communications, 2015, 6, pp.6154. ⟨10.1038/ncomms7154⟩. ⟨hal-01116452⟩