Thank goodness for bad genes

panda by popofatticus

Developmental buffering, or how to live with your bad genes
[Via The Panda’s Thumb]

Mutate. Select. Repeat. Mutate. Select. Repeat. You can’t understand evolutionary biology if you don’t get the significance of that process. And yet, if you think that’s all there is to it, you’re way off track. PZ explained this very nicely here last week. Let’s focus on one simple point that he made, and look at some recent and significant work on that subject that shows just how misleading some of the common simplifications of evolutionary biology can become.

Here’s PZ on simple views of mutation and selection:

Stop thinking of mutations as unitary events that either get swiftly culled, because they’re deleterious, or get swiftly hauled into prominence by the uplifting crane of natural selection. Mutations are usually negligible changes that get tossed into the stewpot of the gene pool, where they simmer mostly unnoticed and invisible to selection.

I think this is an extremely important point, both for those seeking to answer creationist propaganda and for anyone else trying to understand the process of evolutionary change. The common picture, painted all too often by commentators of various stripes, depicts a world in which mutations run a harrowing gauntlet of selection that is likely to foolishly discard both the gems and the proto-gems of biological function. Oh sure, the cream eventually rises to the top, but only through the magic of seemingly endless eons and limitless opportunities.
I hope that most readers of the Panda’s Thumb are annoyed by this crude caricature, but it’s the standard tale, and when the narrator only has a paragraph, it’s the one we’re most likely to hear.

To improve the situation, we might first add the concept of random drift. And that helps a lot. Then we would emphasize the selective neutrality of the vast majority of all mutations, as PZ did. And that helps a lot, too. Let’s look at another helpful concept, one from the evo-devo playbook, almost crazy at first glance but remarkably interesting and important.

Suppose that one reason many mutations are selectively near-neutral is because genetic systems are able to tolerate mutations that have the capacity to be strongly deleterious. Suppose, in other words, that organisms are robust enough to live with seriously nasty genetic problems. This would mean that such mutations could escape selection, and that populations could harbor even more genetic diversity than our simplistic account would seem to suggest.


I mentioned this the other week but the point can not be hit home enough – most mutations have little selective effect on an organism, even if they have a tremendous on the activity of the mutated protein. When I was at Immunex, we noticed this when we deleted the gene for Interleukin-2 in mice. This gene codes for a protein that is required for the growth of important immune cells called T-cells. Yet mice lacking IL-2 seemed normal and healthy.

Few proteins absolutely require the optimal activity to work. There is a lot of redundancy, allowing mutated genes for damaged proteins to stick around. The animal bearing them does not immediately lose the battle of natural selection.

This means that all sorts of altered proteins can be maintained in a population of animals, increasing their genetic diversity. For a species, the best approach for dealing with changing environments is to have a lot of genetic diversity, so that it is likely that at least some of the members of the population will bear genes that now help. Thus, when the environment changes, a species of goby can infiltrate a new ecosystem and thrive.

The work discussed in this post reveal more details about the buffering abilities of genetic systems. It makes sense – organisms that did not have redundant systems would die off easily with just normal mutations. But those which developed ways to cope with suboptimal proteins would continue to thrive.

So, while natural selection would seems to drive a population to a single set of perfect genes, the best response for many species is to find a way to maintain a lot of genetic diversity, especially diversity that can not immediately be selected against. It is a eternal dance between the specificity driven by natural selection and the diversity needed for survival. I’ve discussed how the red deer in Scotland is managing this balance – by interbreeding with another type of deer and spreading those genes amongst 4 possible species instead of one. Or, more accurately, 4 new subspecies representing one type of deer. It has increased genetic diversity, allowing itself to have a greater chance that some of the population will survive a changing environment.

Genetic buffering has been seen in many species. These recent papers have elucidated the process better, giving us further ideas of how an animals genome can buffer itself against deleterious mutations and preserve diversity.

And some of those genes with deleterious mutations may end up being useful in the future, under the right conditions.

I wonder if many species that are having a hard time adapting to the changing environmental conditions seen today have lower levels of genetic and developmental buffering. Perhaps, after this extinction event, most species will have advanced buffering capacities, as that would seem to be the ultimate survival trick.