Academic journal article Genetics

Duplication Frequency in a Population of Salmonella Enterica Rapidly Approaches Steady State with or without Recombination

Academic journal article Genetics

Duplication Frequency in a Population of Salmonella Enterica Rapidly Approaches Steady State with or without Recombination

Article excerpt

ABSTRACT

Tandem duplications are among the most common mutation events. The high loss rate of duplication suggested that the frequency of duplications in a bacterial population (1/1000) might reflect a steady state dictated by relative rates of formation (k^sub F^) and loss (k^sub L^). This possibility was tested for three genetic loci. Without homologous recombination (RecA), duplication loss rate dropped essentially to zero, but formation rate decreased only slightly and a steady state was still reached rapidly. Under all conditions, steady state was reached faster than predicted by formation and loss rates alone. A major factor in determining steady state proved to be the fitness cost, which can exceed 40% for some genomic regions. Depending on the region tested, duplications reached 40-98% of the steady-state frequency within 30 generations-approximately the growth required for a single cell to produce a saturated overnight culture or form a large colony on solid medium (10^sup 9^ cells). Long-term bacterial populations are stably polymorphic for duplications of every region of their genome. These polymorphisms contribute to rapid genetic adaptation by providing frequent preexisting mutations that are beneficial whenever imposed selection favors increases in some gene activity. While the reported results were obtained with the bacterium Salmonella enterica, the genetic implications seem likely to be of broader biological relevance.

TANDEM genetic duplications are probably the most common mutation type in terms of their rate of formation and their frequency in an overnight culture. Roughly 10% of cells in an unselected laboratory culture of Salmonella enterica carry a duplication of some chromosomal region and 0.005-3% have a duplication of a specified gene (Anderson and Roth 1977). The situation may be even more extreme in humans, whose genomes contain hundreds of copy number variations (CNVs) (Sharp et al. 2005; Korbel et al. 2007; Kidd et al. 2008). The phenotypes caused by duplications can be detected by selection and contribute to fitness whenever growth is limited by quantity or activity of a particular protein (Sonti and Roth 1989; Tlsty et al. 1989; Andersson et al. 1998). Selected increases in gene copy number can enhance the likelihood of point mutations that further increase fitness by providing more targets for change (Roth et al. 2006; Sandegren and Andersson 2009; Sun et al. 2009).

Little is known about duplication formation or why duplications are so frequent in unselected populations. Duplications form frequently between separated sequence repeats, suggesting a role for homologous recombination (Figure 1, top). For example, the most frequently duplicated regions of the chromosome of S. enterica are those between copies of the rrn cistrons, with 6.5 kb of nearly identical sequence (Anderson and Roth 1981). In contrast, less common duplications arise between regions with little or no sequence homology, whose formation seems unlikely to require recombination (Kugelberg et al. 2006). The role of recombination in duplication formation has been difficult to assess because previous duplication assays depended on recombination proficiency. New assays described here suggest that duplications can form without homologous recombination even when extensive sequence repeats serve as junction points. Duplication loss occurs at ∼1% per generation and is essentially eliminated in recA mutant strains (Anderson and Roth 1981), which lack a catalyst of strand invasion that is essential to homologous recombination in otherwise normal strains. Exchanges like those leading to duplication loss can also further amplify gene copy number (Figure 1, bottom).

This study was initiated to test the possibility that duplication frequency in a population might reach a steady state dictated by the relative rates of formation (k;^sub F^) and loss (k^sub L^), as diagrammed in Figure 2 (top). Initially, the fitness cost (growth deficit) of duplications was assumed to be small and was not considered. …

Search by... Author
Show... All Results Primary Sources Peer-reviewed

Oops!

An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.