"Adaption through copy number variation of eccDNA in yeast"Dewan, IanExtrachromosomal genetic elements which replicate independently of the core genome and exist in multiple copies per cell form an important component of the genomes of many organisms. This includes plasmids of bacteria, mitochondrial and plastid genomes of eukaryotes, and extrachromosomal circular DNAs (eccDNAs), small circular DNA molecules found in the nuclei of many eukaryotic cells—including normal animal cells, cancer cells from human tumours, and yeasts and other fungi—produced as byproducts of transcription or replication of chromosomal DNA. The multicopy nature of many of these elements means that stochastic effects in the replication and segregation of copes of an extrachromosomal genetic element have important implications for their genetics and effects on their hosts. We develop models of the contribution of gene amplification by eccDNAs to host adaptation. Because they exist in multiple copies and consist of small regions of chromosomal DNA which may contain genes, eccDNAs can be a source of gene copy number variation; if these genes have important fitness consequences for the cell, amplification by eccDNA can serve an adaptive function. This mechanism has been observed in experimental evolution experiments in yeast (Saccharomyces cerevisiae), where one mechanism of adaptation to high concentrations of copper was through the amplification of copper-resistance genes on eccDNA. However, eccDNAs lack mechanisms to control their replication and segregation, unlike plasmids or organelles, and therefore their copy number dynamics are particularly driven by stochastic processes. We develop a stochastic model of the variation of eccDNA copy number in a host yeast population, and combine this with branching process models at the host level to explore the circumstances in which eccDNAs can make an important contribution to the persistence of the host population in novel environmental conditions. |
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