Names are generally very arbitrary things. In the words of The Bard: "A rose by any other name would smell as sweet." This may be true for roses, but for mutations, names carry a great deal of meaning. Beneficial mutations are good, they improve an organism's chances for survival (i.e. raise its fitness). Deleterious mutations are bad, they reduce an organisms chances for survival (lower fitness). One type of mutation is distinctly sweet, the other distinctly wretched.
Mutations are assigned their names when they first appear in a population. A mutation that improves fitness is assumed to be good and a mutation that lowers fitness are assumed to be bad. These name assignments seem nice and neat and simple, but they are predicated on the assumption that a mutation's fate is unalterable. Good mutations are kept, bad mutations are purged by selection, very neat and tidy just as we scientists prefer it.
The picture becomes murkier when you allow for a second mutation that appears on the same genome as the first. That second mutation has the potential to alter the effect of the first. Good mutations may become bad and bad mutations become good (Figure 1).
Figure 1: An example of the two mutation system described above (From Covert et al 2013). Both mutations A and B individually are deleterious, but A and B together are extremely beneficial.
So if a second mutation can alter the effect of the first then all bets are off, right? Classical evolutionary theory doesn't think so, and has held that such infrequent occurrences are probably unimportant. Mutations are rare; getting two mutations is even rarer. Getting the right two mutations, close together, to not only ameliorate a deleterious mutation, but to actually open up new beneficial mutations that weren't accessible before? Pishaw! You get better odds at the blackjack table! So the literature generally holds that bad mutations stay bad, and good mutations stay good, and that's how it's been in evolutionary theory for a long time.[1][2]
Evolution isn't about playing one hand of blackjack though, its about playing lots and lots of hands, over a very long period of time. On a long enough timescale, you will eventually see one of these rare chance events. Deleterious mutations are extremely common, a genotype with a deleterious mutation will persist in the population for a few generations before it's purged. In that short time, if one of that genotype's progeny acquires a second mutation there is a small chance that the two mutations together will actually be good. There is also a possibility that in addition to ameliorating the deleterious effect, the pair of mutations also pushes the population's genotypes closer to other beneficial mutations. These super-compensatory mutations are rare, but have a huge impact when they finally emerge.
The question is not "if" or "when", but of how important these super-compensatory mutations are. Until now this question has been open, but now my colleagues and I have begun to shed light on it. Using self-replicating computer programs (digital organisms) we examine the effects of deleterious mutations in two ways that are not possible with organic study systems.
In our first set of experiments, we replace all deleterious mutations with beneficial or neutral mutations making it impossible for deleterious mutations to appear at all. In contrast, mutations in the population normally occur completely at random with the vast majority of them having deleterious or lethal fitness effects. Surprisingly, when we compare the no-deleterious populations to normal populations we find that the normal populations have much much higher fitness. So, at least some immediately deleterious mutations in the long run are creating a net benefit. But is it all deleterious mutations that are important or just a few?
With our second set of experiments we undid every instance of a deleterious mutation on the lineage from the starting organism to the most successful genotype in each population. Undoing these mutations asks the question "what would have happened without this one mutation?" Throughout all of the populations with deleterious mutations we found rare instances of super-compensatory deleterious mutations, which also lead populations to previously inaccessible beneficial mutations. In other words, occasional steps that are not immediately beneficial may lead to huge rebounds.
This isolation of historically significant super-compensatory mutations is what sets our work apart from other works on the role of deleterious mutations. We actually identify which deleterious mutations are leading to higher fitness in the long run and we measure their impact on the long-term evolution of the population.
The most startling thing we found when we looked at individual super-compensatory mutations, is that they occur in minuscule quantities. Out of 50 replicate populations, each experiencing 45,000 generations of evolution, we found only 36 super-compensatory mutations. Of those 36, only 11 were found to be necessary for the populations' continued evolution. But theses 11 super-compensatory mutations fundamentally altered the outcome of evolution. Without these extremely rare events the evolutionary process stalls out, possibly for very long periods of time.
So the story is not told by the name alone. Every once in a while, a deleterious mutation will interact with other mutations in a way that makes them more beneficial together; interactions such as these are known in the literature as "epistatic" mutatitons. These rare, but historic events are pathways to essential variation in evolving populations that may become evolutionarily stuck otherwise. Furthermore, it's impossible to predict *which* deleterious mutation will be the lucky one. But one thing from my work is clear: deleterious mutations do provide essential variation needed by evolving populations.
Covert, Lenski, Wilke and Ofria (2013) Experiments on the role of deleterious mutations as stepping stones in adaptive evolution. PNAS doi: 10.1073/pnas.1313424110
EDIT (9/5/2013):Correcting minor typos
Cool ideas, but don't forget that things like ecology play a role, too. For example, if the selection pressures change and begin to favor what was labeled a deleterious mutation, then the deleterious mutation will increase fitness. Another example would be a deleterious mutation that affects an unused character; it's not bad, but it's not good, either. Mutations are not easily defined as good and bad; often, they're simply neutral. The effect depends on both the other genes of the organism with which a mutation can interact, as well as the selective environment in which the mutation takes place.
ReplyDeleteHi Choosy,
DeleteThanks for you comments! You raised a lot of good points, many of which we're working on in follow up literature.
You're correct in that ecology does play a role, and we've actually begun addressing that in a paper in last year's alife: http://artcovert.is-a-teacher.com/al13_paper1.html. This paper will be the subject of a blog post in the near future.
Changing the environment during our replacement experiments would be computationally expensive (long story). So we haven't done that experiment directly, but we're working on it! Stay tuned!
As to unused characters (or unexpressed characters), if the character has no impact on the fitness of its phenotype then any mutations effecting *only* that character will be neutral, not deleterious. There's nothing in our experiments that prevents neutral mutations from becoming beneficial via epistatic interactions. However, as you point out, our environment isn't changing, so we won't see any shifts from neutral to beneficial (or deleterious) from ecological interactions.
Bear in mind that while most mutations that reach fixation in populations are neutral, those neutral mutations are only a fraction of mutations that actually occur. The vast majority of mutations are deleterious or lethal, and will be purged by selection unless they are rescued by epistatic interactions (as we discuss in the paper). The window of time for that compensatory mutation to rescue a mutant is very narrow; the second mutation must occur during those few generations it will take for selection to wipe out the deleterious mutant.
As I said, super-compensatory pairs are extremely rare events, brought to the forefront by random chance, but when they do occur they occur in only a few generations. In many cases environments are stable long enough for super-compensatory pairs to emerge. Ecological shifts will eventually occur making a particular pair irrelevant... but as Jared and I showed in the Alife paper I linked to, even when the environment changes, deleterious mutations can still be important!