I promised to discuss “evolutionary rescue” – the ability of populations to adapt to environmental change so that they do not go extinct. Like many terms in evolutionary biology this should not be taken anthropomorphically – there is no rescuer. However it is relevant in an era of anthropogenic extinctions and evolution of antibiotic resistance (where extinction, or at least population size reduction, is the desideratum). The concept gets the experimental evolution treatment in this recent Nature paper in which 1255 replicate E. coli B populations were evolved under varying regimes of exposure to the antibiotic rifampicin.
Lindsey et al. examined the effect on population survival of varying the rate of change of the environmental driver. Populations were exposed to concentrations of rifampicin that increased at different rates: suddenly, gradually or moderately. Amusingly and aptly the authors cite the Reverend William Dallinger’s 19th century experiment in which “minute septic organisms” (protists) were evolved to resist elevated temperatures that individuals from the original population could not survive. In the new study sudden increases in rifampicin also frequently caused population extinction, but populations were more resilient when changes occurred gradually. What makes this paper particularly interesting is Lindsey et al.’s examinations of the reasons for this.
Broadly there are two reasons why population survival is increased under more gradual change:
1. Under less severe pressure the population is larger. So, in a given time, the probability of sampling beneficial mutations is higher. (Note that beneficial mutations are also less likely to be lost under drift in larger populations – something not discussed in the paper).
2. Transient moderate conditions may also open up new evolutionary paths through “stepping stone” mutations.
Point number 2 is not as obvious as it appears. As the researchers argue it requires the presence of genetic and gene-environment sign epistasis. Sign epistasis describes the situation in which the direction of the effect of an allele changes depending on the background. For example, imagine two loci: a and b, with alleles (A or a) and (B or b), respectively (and think haploid). We have an instance of sign epistasis if allele A reduces fitness on a b background, but it increases fitness on a B background. What this means is that, when starting with the ab genotype, an AB genotype is inaccessible assuming one-step mutations only (that is if B behaves in the same way and is costly on an a background). In fitness landscape terms, we have to cross a valley to get to a peak = ruggedness. If this is the situation at a high antibiotic concentration then higher fitness is inaccessible. But crossing the valley is possible if the effect of an allele changes direction depending on the environment = gene-environment sign epistasis. For example, there would need to be an environment in which A increases fitness on a b background (opposite to the above description). When intermediate antibiotic concentrations provide this environment they open up new paths to adaptation – and increase the probability of population survival. If my explanation is confusing examine figure 3 in the paper.
I said Lindsey et al. gave the experimental evolution treatment to evolutionary rescue. Accordingly the authors do what is only possible within this paradigm: they reconstruct ancestral genotypes, and combinations thereof, and they expose them to varied antibiotic concentrations. Data thus collected showed that, in at least some gradually changing lineages, sign epistasis occurred (with the caveat that genotype information was limited to a single gene). Stepping stone mutations were identified that were deleterious at high rifampicin concentrations but beneficial at intermediate concentrations, while combinations of these alleles demonstrated enhanced fitness at higher concentrations (although not always at the maximal concentration, figure 4). Of course the two explanations for evolutionary rescue listed above are quite likely to operate simultaneously as the authors allow.
With respect to reversing environmental damage (mentioned in my last post) these results are interesting but not conclusive. For example, it is possible that evolution to resist environmental change will result in higher fitness even when that change is reversed (as implied by the idea of a fitness valley). But since we have acknowledged the existence of gene-environment epistasis it is also possible that the fitness of resistance alleles is lower in absence of the selective pressure (this is shown in the paper’s figure 3a where the AB genotype has low fitness in environment x). In the case of antibiotic resistance it may be more reasonable to assume that resistance carries a cost in the absence of a drug. If it does and if susceptible and resistant strains co-exist, it is wise to reduce the duration of treatment contra medical orthodoxy.
Finally it is worth noting that extinction can occur from intrinsic (mutational) causes such as Muller’s Ratchet (in small populations) and deterministic mutation accumulation (in any population). In a sense we have here a special case of the problem of induction in that any extant population is descended from an extinction-resistant lineage – but we also know that extinction is very common in the history of life and that we live in an era of unprecedented environmental change.