Academic journal article Genetics

Adaptive Molecular Evolution for 13,000 Phage Generations: A Possible Arms Race

Academic journal article Genetics

Adaptive Molecular Evolution for 13,000 Phage Generations: A Possible Arms Race

Article excerpt


Bacteriophage φX174 was evolved on a continuous supply of sensitive hosts for 180 days (~13,000 phage generations). The average rate of nucleotide substitution was nearly 0.2% (11 substitutions)/20 days, and, surprisingly, substitutions accumulated in a clock-like manner throughout the study, except for a low rate during the first 20 days. Rates of silent and missense substitutions varied over time and among genes. Approximately 40% of the 71 missense changes and 25% of the 58 silent changes have been observed in previous adaptations; the rate of parallel substitution was highest in the early phase of the evolution, but 7% of the later changes had evolved in previous studies of much shorter duration. Several lines of evidence suggest that most of the changes were adaptive, even many of the silent substitutions. The sustained, high rate of adaptive evolution for 180 days defies a model of adaptation to a constant environment. We instead suggest that continuing molecular evolution reflects a potentially indefinite arms race, stemming from high levels of co-infection and the resulting conflict among genomes competing within the same cell.

MOLECULAR evolution is an established fact, but the relative contributions of various factors to that evolution remain controversial (KiMURA 1983; NEI 1987; GILLESPIE 1991; Li 1997). Advantageous, neutral, and even deleterious mutations can become common in a population, and their respective rates of evolution depend on mutation, the strength of selection, and population size, plus the influence of other loci through linkage and epistasis. While much of the work in the field has focused on neutral evolution, a current goal is to identify adaptive evolution by finding its signatures in molecular data. Yet despite considerable evidence of adaptive molecular evolution, much uncertainty remains about the nature of the selective agents.

Toward the goal of revealing the diverse mechanisms of molecular evolution, we have conducted several experimental studies of bacteriophage evolution (BULL et al 1997, 2003; WICHMAN et al 1999, 2000; GRILL et al 2000; HOLDER and BULL 2001). In some of those studies, phages were grown in continuous culture of a two-stage chemostat, whereby actively growing, sensitive bacteria were continuously pumped into a vessel containing phage, allowing the phage to infect and reproduce as if their population were expanding exponentially (BULL et al 1997; WICHMAN et al 1999, 2000). Populations of those phages accumulated nucleotide changes over the duration of the continuous culture, but those previous studies tended to be short (mostly 10 or 11 days, with approximately three phage generations per hour). The nucleotide changes in those systems exhibited characteristics of adaptive evolution: a high rate of missense/ silent substitution and high rates of parallel changes. Where the phenotypic effects of changes were identified, they could be interpreted as facilitating phage growth under the culture conditions (BULL et al. 2000; GRILL et al 2000).

To further explore the nature of molecular evolution in this system, we now report on a much longer duration of phage growth in continuous culture. In addition, the culture conditions are more benign and are meant to approximate "control conditions," which should impose less selection for change. By conducting a longer adaptation with frequent sampling of the population, the temporal characteristics of molecular evolution may now be studied. If adaptation in this system is primarily to the constant ("control") culture environment, we expect that the initial rate of molecular evolution will be low and then wane as fitness approaches its maximum (FISHER 1958; GILLESPIE 1983, 1984; ORR 1998, 2002).

In two previous adaptations to inhibitory conditions, an initial high rate of molecular evolution decreased by 66 and 80% during extended adaptation in the same environment (BULL et al. 1997), supporting the theoretical expectations of a plateau. …

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