ena-STUDY-INSTITUT PASTEUR-03-12-2014-17:10:56:742-144
Macrotene chromosomes provides insights to a new mechanism of high-order gene amplification in eukaryotes
Copy number variation (CNV) 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, that we propose to call macrotene, whose characteristics suggest the products of intra-chromosomal rolling-circle type of replication structures, probably initiated by increased accidental template switches under important cellular stress conditions.
Copy number variation (CNV) 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, that we propose to call macrotene, whose characteristics suggest the products of intra-chromosomal rolling-circle type of replication structures, probably initiated by increased accidental template switches under important cellular stress conditions.