11 January 2006

Applications of Evolution 3 - tradeoffs in resistance.

Someone just emailed me a copy of an interesting press release. Some time back, a particular mutation known as CCR5delta32 was identified as conferring greatly increased resistance to HIV in individuals who had two copies of that particular gene (in geek terms, those are individuals homozygous for that particular allele). According to the press release, a group of researchers have discovered that this resistance to HIV comes with a price. The individuals who are homozygous for the CCR5delta32 allele do have greatly increased resistance to HIV, but they also have greatly decreased resistance to the West Nile Virus.

This is interesting (to me, anyway) for a number of different reasons.

First, it shows that whether or not a particular mutation is beneficial, neutral, or harmful doesn't just depend on what the mutation does. It also depends on the conditions that the organism lives in. If this mutation is found in someone who lives in an area where West Nile is absent but HIV is common, then this is a beneficial mutation. If the same exact set of genes are found in someone living in an area where West Nile is common and HIV rare or absent, then the mutation is harmful. The environment is almost always important in determining the net effect that a particular mutation is likely to have on the organism.

I should probably stop for a second to make clear what I mean when I use the word "environment." In this case, I'm not just talking about the climate, or pollution, or the effects that humans are having on the natural world. In evolutionary biology (and ecology and other contexts), the "environment" that a particular organism lives in includes everything outside of the organism that has an effect on it. This includes the climate, of course, but it also includes things like predators, competition with other members of the same species, the presence or absence of alternative food sources, and a host of other such things.

In our case, as a species, our environment includes the various disease-causing agents that we are exposed to. As is the case with other environmental factors, like average temperature and rainfall, this factor can vary widely from one geographical location to another. This is true at both large and small scales. On a large scale, for example, leptospirosis is relatively common in Hawaii, but it is pretty much absent in the Northeastern US. On a smaller scale, strains of bacteria that are resistant to multiple antibiotics are more common in hospitals than they are in most homes.

If you want to look into this further, it gets more complex and more interesting, because pathogens are organisms too (that's arguable with viruses, but for these purposes they act like organisms so we'll treat them as such). Anyway, pathogens are organisms, and whether or not a particular mutation in a pathogen is beneficial will depend on the pathogen's environment. For pathogens that impact humans, humans are an environmental factor. Let's say that a strain of HIV mutates in a way that lets it attack people who have the CCR5delta32 resistance. Is that mutation beneficial? Maybe, but maybe not. It's going to depend on whether or not this gain comes with a corresponding cost, and whether the cost is worth the gain. That's going to depend in part on how common people expressing CCR5delta32 resistance are in that area.

Situations like this are things to keep in mind when you hear creationists and ID proponents making arguments like, "almost all mutations are harmful." Life is complex, environments are complex, and the relationships between organisms and environments are extrordinarily complex. The effects of a mutation will depend on an enormous range of factors, and a change in just one external factor can make a harmful mutation beneficial, or a beneficial mutation harmful.

In this case, this mutation was pretty clearly beneficial in North America just a few years back. Anyone who had two copies of the gene with this mutation was resistant to HIV, and until fairly recently West Nile wasn't present here, so the lack of resistance to West Nile wasn't a big problem. Now, it is entirely possible that the mutation is more harmful than helpful. Both HIV and West Nile are relatively uncommon in the US, but HIV transmission can largely be prevented as long as care and common sense are used, while West Nile transmission takes place through an insect vector, and is much harder to prevent. With West Nile now present in almost the entire country, we may well have seen this mutation change from being beneficial to harmful within just a couple of years.

Whether or not a particular mutation is helpful or harmful is very important to evolutionary studies, because it helps determine whether or not that particular mutant form (allele) of the gene is likely to spread, and whether it is likely to spread through the entire population or just certain geographic areas. If the allele is helpful in some locations and harmful in others, it can actually lead to a situation in which you get genetic differences in different areas of the population. That's cool, because it is one of the many scenarios that can lead to one species dividing into two.

This is a pretty cool finding, even if it isn't good news for the HIV research and treatment community. It has definitely taught us some things that are going to be really important to infectious disease specialists - not least, that the CCR5-inhibitors that are currently being tested in clinical trials may have a really big down-side - but also because it can give us some insight into the complex nature of the interactions between our genes and the environment, and how that impacts evolution.
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