Evolution is powerful. From a single cell, it generated the astonishing diversity of life on our planet. Yet there are also all kinds of constraints shaping evolutionary processes and limiting evolutionary possibilities. They can be genetical, developmental or physiological. So given these constraints, is it possible for evolution to take the same trajectory twice? Or let’s put it more boldly, can we even predict evolution? A recent study on the parallel evolution of dauer formation resistance in three different lab Caenorhabditis strains lends a positive answer.
The well-known model organism Caenorhabditis elegans and many other nematode species have two alternative developmental strategies to choose when they were young: 1) rapid developing into an adult within three days or so and die soon after their reproduction. 2) entering the so-called dauer larva stage in which they suspend their development for withstanding various stresses in the environment, such as food shortage, heat, or high population density. Caenorhabditis use their pheromone receptors to monitor the alarming signals accumulated in the population and trigger the dauer formation whenever necessary (e.g. when population density is too high). This system works well for wild nematodes. For the lab strain, however, crowded population does not mean limited food sources any more, which releases the necessity for shifting to the dauer stage at a cost of giving up reproduction opportunities. Not surprisingly, some lab strains gradually lost their dauer stage switching ability in the presence of crowded signals and will just keep growing and reproducing. Two C. elegans strains, LSJ2 and CC1, are such examples. These two strains, together with the standard lab strain, N2, are all descendents of the same C. elegans ancestor. Yet in contrast to N2 and the ancestral strain, LSJ2 and CC1 strains show no response to the N2 dauer formation pheromone, ascarosides. According to their isolation time relative to N2 strain, independent mutations should account for this parallel phenotypic changes.
In order to clarify the genetic basis behind the scene, the authors constructed 94 N2-LSJ2 recombinant inbred lines (RILs), an LSJ2-N2 and a CC1-N2 near-isogenic lines (NILs) for quantitative trait locus (QTL) mapping. There are four ascarosides (C3, C5, C6 and C9) that can induce the dauer formation of N2. In this study, the author focused on C3, of which the resistance seems to be controlled by a single locus. Further experiments pinpointed a ~10kb region on the X chromosome as the candidate C3 resistance locus. Within this region, a 4,906-bp deletion in LSJ2 strain and a 6,795-bp deletion in CC1 strain, both of which span across two putative G-protein-coupled receptor genes (srg-36 and srg-37), aroused most attention.
A series of assay showed that srg-36 and srg-37 both encode chemoreceptors (or subunits of chemoreceptors) of the C3 ascaroside, although with somewhat functional redundancy. For example, transgenic assay of these two genes or the genomic region covering them can reactivate the C3-induced dauer formation of C. elegans from LSJ2-N2 and CC1-N2 NILs. By using a GFP to label srg-36 and srg-37, the authors are able to trace the expression location of them in vivo and they found that they were primarily expressed in the sensory cilia of ASI neuron, which is the critical regulator of dauer formation. The misexpression assay of srg-36 and srg-37 in ASH neuron showed rapid and significant response of Ca2+, which is a good indicator of these two genes’ chemoreceptor functions. Taken together, the adaptive evolution of C. elegans lab strains repeat itself in terms of C3 resistance by undergoing the same genetic changes.
What makes this story more exciting is the authors found that this parallel evolution driven by the same genetic basis can not only happened in different strains of the same species, but across different species as well. As a sister species, Caenorhabditis briggsae diverged from C. elegans about 20-30 million years ago. Its genome does not have a one-to-one orthologous relationship with srg-36 or srg-37, but has multiple copies of srg paralogous genes instead. Similar to LSJ-2 and CC1 of C. elegans, the DR1690 strain of C. briggsae also lost their response to ascarosides when cultured with high population density. The investigation of DR1690 showed that a 33-kb deletion in its genome disrupted a srg paralog gene named CBG24690, which led to such phenotypic change. According to the authors experiment, CBG24690 encodes the C3 chemoreceptor in C. briggsae, which plays a comparable role as srg-36/srg-37 in C. elegans. And roughly the same genetic change turned off the dauer formation ability of C. briggsae DR1690 strain in crowded environment as it did in two C. elegans strains independently. Now what’s the chance of that?
There are no doubt that there are many genes participating the pheromone sensing of Caenorhabditis species. Theoretically, mutations on many, if not any, of them can convey the resistance to the corresponding pheromone (e.g. C3 in this case). The chance of parallel evolution driven by mutations on essentially the same gene three times independently is obviously too low. Yet this is what we observed here. The tape of evolution was played more than once. We normally think evolution as a pure opportunist and the evolutionary processes are dominated by randomness and contingency. There are simply so many potential paths or trajectories to take, the result of which seems to be unpredictable. The discovery made in this study may shed some optimistic light on us: at least in some cases, evolution can be predictable.
PT McGrath, Y Xu, M Ailion, JL Garrison, RA Butcher, CI Bargmann. 2011. Parallel evolution of domesticated Caenorhabditis species targets pheromone receptor genes. Nature. 477:321-325. doi:10.1038/nature10378.