PT  - JOURNAL ARTICLE
AU  - Judith Ilhan
AU  - Anne Kupczok
AU  - Christian Woehle
AU  - Tanita Wein
AU  - Nils F. Hülter
AU  - Philip Rosenstiel
AU  - Giddy Landan
AU  - Itzhak Mizrahi
AU  - Tal Dagan
TI  - Segregational drift and the interplay between plasmid copy number and evolvability
AID  - 10.1101/369579
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 369579
4099  - http://biorxiv.org/content/early/2018/10/21/369579.short
4100  - http://biorxiv.org/content/early/2018/10/21/369579.full
AB  - The ubiquity of plasmids in all prokaryotic phyla and habitats and their ability to transfer between cells marks them as prominent constituents of prokaryotic genomes. Many plasmids are found in their host cell in multiple copies. This leads to an increased mutational supply of plasmid-encoded genes and genetically heterogeneous plasmid genomes. Nonetheless, the segregation of plasmid copies into daughter cells during cell division is considered to occur in the absence of selection on the plasmid alleles. We investigate the implications of random genetic drift of multicopy plasmids during cell division – termed here segregational drift – to plasmid evolution. Performing experimental evolution of low- and high-copy non-mobile plasmids in Escherichia coli, we find that the evolutionary rate of multicopy plasmids does not reflect the increased mutational supply expected according to their copy number. In addition, simulated evolution of multicopy plasmid alleles demonstrates that segregational drift leads to increased loss frequency and extended fixation time of plasmid mutations in comparison to haploid chromosomes. Furthermore, an examination of the experimentally evolved hosts reveals a significant impact of the plasmid type on the host chromosome evolution. Our study demonstrates that segregational drift of multicopy plasmids interferes with the retention and fixation of novel plasmid variants. Depending on the selection pressure on newly emerging variants, plasmid genomes may evolve slower than haploid chromosomes, regardless of their higher mutational supply. We suggest that plasmid copy number is an important determinant of plasmid evolvability due to the manifestation of segregational drift.