Tuesday, February 06, 2007

Molecular hopeful monsters?

When I took evolutionary theory as an undergraduate one of the concepts we learned about was that of of a hopeful monster-a radically new form of an organism arising, say by mutation. The hopeful part refers to the idea that these abruptly produced form might be adaptive in it's environment. The prevailing thought today is that this sort of leap probably doesn't happen at least not in the way envisioned by it's proponents.

A recent paper by Joanna Masel in Genetics 172:1985-1991(2006) takes a fresh look at the hopeful monster issue in terms of a model of two types of mutations that she calls "Hopeful monster" mutations and conversely "hopeless monster" mutations. Her use of these terms is crucially different than other uses because they refer to the fitnesses of the mutations rather than to a large phenotypic change. A "hopeful monster" mutation has reduced fitness in most environments but only slightly reduced fitness and may be adaptive in certain rare circumstances if the environment changes. "Hopeless monster" mutations have greatly reduced fitness in all environments.

Most of the time, both types of mutations ought to decrease in frequency relative to the alleles with the highest fitness in a particular environment. But what about when the population is subject to reduced selection for a time? Various authors cited by Masel have speculated that this sort of reduced selection, or as she terms it "shielding" may lead to a build up of potentially adaptive combinations of mutations when the environment changes and the mutations then become subject to natural selection. But she notes that this idea is controversial; After all if a population is adapted to it's environment then it is unlikely that a mutation will arise that will make it more adaptive.

From the point of view of her model, both sorts of mutations may accumulate when selection is muted or "shielded" but possibly adaptive combinations of "hopeful monster" mutations might be swamped by the fitness effects of hopeless monster mutations.

Masel investigates a simple model of a haploid population and she makes a number of simplifications to make the mathematics tractable, a very common strategy in population genetics. Indeed rather than being just two classes of mutations based on fitness effects it is more likely that there is a broader range of fitness distributions. She also assumes that the shielding or 'hiding' parameter S2 is constant across all mutants. So for instance in terms of selective coefficients, the fitness of a "hopeful monster" allele would be 1-S1*S2 where S1 is a small selection coefficient. For a hopeless monster allele a corresponding fitness would be 1-S2 since she makes the simplifying assumption that when these alleles are lethal. This may seem confusing but if the hopeless monster mutant is lethal then its corresponding selective coefficient when S2 is one is itself 1.0.

Another assumption she makes and one I wonder about is an assumption that environmental change is rare relative to the time scale of genetic drift, something that may not be true for very large populations. However this seems a conservative assumption since large populations are exactly the sort of populations where her model ought to work best, if it is going to work at all.

Her simplified model yields some interesting results. First of all her results suggest a Goldilocks effect with respect to when selection is weakened (S2 <>> 1/U. Again this makes some sort of sense, if most mutations that arise are of the hopeless monster sort, then it should difficult for potentially adaptive mutations to be maintained as part of the variation when selection is weakened.

What is really interesting is that the amount of potentially adaptive cryptic genetic variation that accumulates when selection is shielded is increased as deleterious mutations accumulate when selection is weak. This affect is enhanced, according to her model, for adaptations that might require particular combinations of mutations. She claims this is relevant to theoretical attempts to estimate the rate at which adaptive combinations of mutants might arise, which she sees as significantly underestimating this rate because the do not account for the enrichment of "cryptic" genetic variation when selection is relaxed.

She then discusses some situations where her model's concepts might apply. For instance yeasts have a prion called PSI+ that when it appears, clumps the non prion protein Sup35, depleting this protein. Sup35 is a termination factor for translation so the effect of removing this protein is to cause the ribosome to increase the rate at which it reads through the normal termination site, exposing cryptic variation presumably in the normally untranslated trailer region of the RNA.

It seems to me that good experimental systems might involve domestication especially in animals where domestication often seems to lead to relaxed selection on certain aspects of the phenotype. Presumably the affects of relaxed selection could be investigated in yeast or bacterial systems to mimic the effects of domestication. Her model is also relevant to the concept of preadaptation to which the term exaptation is applied today. She notes that the sort of cryptic variation she discusses can be "coopted" in the same way that a trait adapted for one function is often adapted for another function. Indeed she seems to be arguing for a use of the word preadaptation for populations in which the sort of enrichment of cryptic variation she postulates has taken place.

She also sees her work as relevant to an important theoretical question namely whether or evolvability itself can evolve. In other words perhaps mechanisms that allow populations to tap into hidden variation or otherwise evolve more rapidly might themselves might evolve. Personally I have been skeptical of this sort of thing, but maybe it is worth another look.

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