Viral Evolution

By Mubasher Ahmed, Genetics ‘15

Viral evolution is an emerging field in biology that has great implications for human health. T7 is a phage virus, meaning it infects bacteria, and is a powerful model system in evolutionary virology. In a recent experiment, a team of biologists sought to understand the degree to which genetic elements engineered into the T7 phage genome affected the phage’s rate of propagation. In this context, the genetic elements are sequences of DNA that are inserted between genes that allow for researchers to manipulate gene regulatory networks. This allows biologists to probe how phenotypes change when gene-gene interactions are perturbed.  Previous studies had shown that such genomic elements led to decreased fitness for the virus, but these investigators hoped to better understand how exactly such a system would evolve in laboratory conditions.

To address their questions, the scientists grew both T7 viruses with and without design elements in each of two conditions. One condition was in a nutritious broth that used one intestinal bacterium as a host, and the other in a glucose sugar medium that had a different host bacterium. Both T7 strains were allowed to grow for 700-1000 generations in the glucose media and 100 generations in the broth media. Limitless bacteria were provided for the phages in order to encourage growth, and the researchers hypothesized that their experiment would allow enough time for the maladapted viruses to slough off deleterious design elements through evolutionary adaptation.

A growth rate assay of both T7 strains before and after the experiment added insight into the changes in fitness of the evolved populations. The results of the assay showed that the fitness levels of the engineered T7 strains were much closer to the wild-type strains after the experiment than before, indicating successful adaptation. They also compared the genomes of the strains before and after the experiment to pinpoint where evolution had occurred.

The researchers found that the broth-reared viruses retained 45 of 65 design elements while the glucose-reared populations kept 40 of the 60 elements. Curiously enough, there were regions in the wild-type T7 that were also lost in the engineered T7 over evolutionary time. Furthermore, one such region contained approximately nine of the design elements in the engineered genome, suggesting that the evolutionary conditions favored the deletion of that region irrespective of design elements. The results also showed that the wild-type T7 strain raised in the glucose medium exhibited a greater degree of molecular evolution (as measured by DNA sequence changes) than the engineered strains. The researchers did raise the point, however, that the genetic differences between the wild-type and engineered strains could be a result of the design elements altering the type of sequence changes that are beneficial, rather than causing primary fitness effects. Of primary interest was that, due to a lack of gene addition or deletion, the engineered elements reduced fitness by altering gene regulation rather than gene number.

 

Springman R, Molineux IJ, Duong C, Bull RJ, and Bull JJ. 2012. Evolutionary Stability of a Refactored Phage Genome. ACS Synth Biol 1(9): 425-430

Image credit:

Phoebus87 at en.wikipedia [GFDL (http://www.gnu.org/copyleft/fdl.html), CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/) or CC-BY-SA-2.5-2.0-1.0 (http://creativecommons.org/licenses/by-sa/2.5-2.0-1.0)], from Wikimedia Commons