Keep Calm and Evolve On

Lauren Richardson, Associate Editor for PLOS Biology, discusses a new paper published in the journal.

We generally think of evolution as a beneficial process, letting organisms adapt and excel in new and different environments. But as we all know, not all change is good. Deleterious mutations are common in natural populations, and often piggy-back on adaptive, beneficial mutations. When a harmful mutation crops up in the genome, restricting or altering an organism’s ability to function well, evolution must respond to restore the ideal condition. The main way this is done is through compensatory evolution, where the effects of detrimental mutations are compensated by other mutations elsewhere in the genome. In a recent study published in PLOS Biology, a group based in Szeged, Hungary, led by Csaba Pal, characterized – on a massive scale – how compensatory evolution is able to restore peace and harmony after a disruptive genomic event, gene loss.

Saccharomyces cerevisiae (baker’s yeast), in lab conditions, likes to double every one-and-a-half hours. You could practically set your watch to a happily growing culture. Deletion of certain genes, however, will slow yeast’s growth rate. Slow growth is a highly unfavorable state for a yeast, as it’s in direct competition with neighboring yeasts in a culture (or on a rotting apple). Slower growth means a higher chance of getting swamped out of a population. To combat this, compensatory evolution leads to additional mutations in the genome to restore fitness. But how does this process work?

Using the awesome power of yeast genetics, the authors characterized 180 slow-growing yeast strains, each one missing a single gene. Amazingly, they found that nearly 70% of the strains were able to improve their growth rate following laboratory evolution experiments. The authors grew the yeast for 400 generations, which, if these yeasts were humans with a 20-year generation time, would be roughly equivalent to 8000 years! The 180 missing genes covered a wide range of molecular processes, showing that evolution can solve almost any kind of genetic problem.

The authors did their studies in quadruplicate, meaning that for each gene deletion they grew four independent cultures. By sequencing the genomes of evolved strains, they found that, in general, each independent culture used different compensatory mutations to fix the same slow-growth problem. Interestingly, by comparing gene expression profiles, they found that the compensatory fix never restored the original state. Instead the yeast found new ways to regain optimal growth – a workaround instead of a faithful restoration. The effects of these diverse fixes were revealed when they grew the evolved strains in various stressful conditions – each independently evolved strain responded differently. This demonstrates how gene loss can “drive populations to new adaptive peaks,” and can make them potentially better or worse suited to a new environment.

And because all biological studies can be tied in to cancer biology (see anyone applying for postdoctoral funding), I should mention that gene loss events are frequent during tumorigenesis. From these studies you could hypothesize that a gene loss event early on in tumorigenesis could drive compensatory mutations that might promote an increased growth rate and adaptation to the completely crazy tumor microenvironment. But to yeast geneticists, their first thought is probably: what does this mean for the knock-out collections? It means you should probably freeze them down. FAST.

Szamecz, B., Boross, G., Kalapis, D., Kovács, K., Fekete, G., Farkas, Z., Lázár, V., Hrtyan, M., Kemmeren, P., Groot Koerkamp, M., Rutkai, E., Holstege, F., Papp, B., & Pál, C. (2014). The Genomic Landscape of Compensatory Evolution PLoS Biology, 12 (8) DOI: 10.1371/journal.pbio.1001935