28 January 2009

Mendel's Garden here this weekend

The 28th edition of Mendel's Garden, a genetics blog carnival, will appear here at Quintessence of Dust on Sunday. Please send submissions, whether you wrote them or not.

07 January 2009

Christianity & the Scottish Enlightenment

That's the name of our January term course, a trip to London and Edinburgh to learn about the Scottish Enlightenment and its relationship(s) to Christian belief. We'll be keeping a blog with pictures and reflections. So nothing on QoD till the end of the month.

In the meantime, share Mike Beidler's several minutes of fame. Then maybe read up on experimentally-induced out-of-body experiences. And don't miss Ken Miller's three-part series on the latest crap from the ID movement. And if you live in London or Edinburgh, think about dropping by to say hi. See you in three weeks!

06 January 2009

Mendel's Garden #27

Mendel's Garden is a genetics blog carnival overseen by Rich over at evolgen. The new edition is up at Another Blasted Weblog and there's some excellent stuff in there, including some very Mendelian tidbits. Next month's edition will be right here at Quintessence of Dust.

04 January 2009

Quintessence of Dust anthologized again

Well, wow, for the second year now one of my posts has been selected for inclusion in the science blogging anthology, The Open Laboratory. Last year it was the teosinte review; this year the honor goes to the post on Darwin's tomatoes. This year's anthology includes 50 blog posts on various scientific topics, and it looks like an excellent collection.

Thanks to Bora for his hard work as editor of the series and to Jennifer Rohn who is editing this year's edition. And thanks to Elsevier, which has granted free permission to reproduce part of a figure from the Current Biology article that I discuss in the post.

01 January 2009

Clone wars, or how evolution got a speed limit

The standard simplified narrative of evolutionary adaptation goes something like this. A population of organisms is exposed to a challenge of some kind. Perhaps a new predator has appeared on the scene, or the temperature of the environment has ticked up a degree or two, or the warm little pond is slowly accumulating a toxic chemical. Some of the organisms in the population harbor (or acquire) mutations – so-called beneficial mutations – and these individuals are more successful in the face of the challenge. The population evolves, then, as these beneficial mutations become more common until they are the new status quo. The change is brought about by selection, and the process is called adaptation.

These beneficial mutations, as one might suppose, are quite rare. Most mutations are either harmful to some degree or have little or no effect. Since the good stuff is so hard to come by, it follows that huge populations will be better able to adapt, and will do it faster, because they contain more of the good stuff.

It's a straightforward conclusion, and it's the basis of some recent challenges to evolutionary theory coming from the Intelligent Design movement. But it's mostly wrong. ResearchBlogging.org Here's the problem with the simple story.

In a very large population, many beneficial mutations will be present at the same time, in different individuals. When the challenge is presented, these beneficial mutants will compete against each other, and typically one will win. This means that most beneficial mutations – specifically those with small effects – will be erased from the population as it adapts. So, seemingly paradoxically, a very large population doesn't benefit from its bounty of beneficial mutations when it is subjected to an evolutionary challenge. It's as though adaptation has a built-in speed limit in large populations, and the effect has been clearly demonstrated experimentally. It's called clonal interference.

As geneticists examined this phenomenon, it became clear that any attempt to measure beneficial mutation rates would have been influenced, perhaps dramatically, by clonal interference. Such experiments were often done in bacteria, in the huge populations that can be so easily generated in the lab. Analyses in bacteria, published 6 or 7 years ago, had estimated the beneficial mutation rate to be about 10-8 per organism per generation. (That's 1 per 100 million genomes per generation.) Since the overall mutation rate is estimated to be about 10-3 per organism (a few per thousand genomes per generation), it was concluded that beneficial mutations are fantastically rare compared to harmful or irrelevant mutations.

Creationists have long emphasized the rarity of beneficial mutations, for obvious reasons. For their part, geneticists knew that clonal interference was obscuring the true rate, but no one knew just what that rate might be. That changed in the summer of 2007, when a group in Portugal (LĂ­lia Perfeito and colleagues) published the results of a study [abstract/full-text DOI] designed to directly address the effect of clonal interference on estimates of the beneficial mutation rate. Their cool bacterial system (based on good old E. coli) enabled them to genetically analyze the results of an evolutionary experiment, using techniques similar to those made famous by Richard Lenski and his colleagues at Michigan State University.

In short, Perfeito et al. took populations of bacteria and allowed them to adapt to a new environment for 1000 generations. Then they looked for evidence of a "selective sweep" in which one particular genetic variant (i.e., mutant) has taken over the population (their system was set up to facilitate the identification of these adaptive phenomena). The same system had been used before to estimate the beneficial mutation rate, and had arrived at the minuscule number I mentioned before.

The Portuguese group introduced one simple novelty: they studied adaptation in the typical large populations, but also in moderately-sized populations, and then compared the results. The difference was profound: the beneficial mutation rate in the smaller populations was 1000-fold greater than that in the very large populations. This means that clonal interference in the large populations led to the loss of 99.9% of the beneficial mutations that arose during experimental evolution. And that means that the actual beneficial mutation rate, at least in bacteria, is 1000 times greater than the typically-cited estimates.

Perfeito et al. further exploited their system to measure the fitness of all of the mutant clones that they recovered. They found that evolution in very large populations generally resulted in beneficial mutations with larger beneficial effects. This makes sense: the slightly-beneficial clones were eliminated by competition, so at the end of the process of adaptation, we're mostly left with the more-beneficial mutations.

Now some comments.

1. It might seem at first that the large populations are still better off during adaptation, since they do generate beneficial mutations, and selectively retain the more-beneficial ones. But the claim is not that large populations don't adapt; the point is that the vast majority of possible adaptive trajectories are lost due to competition, such that only the trajectories that begin with a relatively large first step are explored. That's a significant limitation, and quite the opposite of the simplistic models of design proponents like Michael Behe and Hugh Ross. Genetic models have shown that the only way for an asexual population to get around the barrier is to do what Michael Behe claims is almost impossible: to generate multiple mutations in the same organism. And recent experimental results show that this does indeed occur.

2. Since the early days of evolutionary genetics, the genetic benefits of sex have been postulated to include the bringing together of beneficial mutations to create more-fit genetic combinations expeditiously. In 2002, an experimental study validated this conjecture, showing that sexual reproduction circumvents the "speed limit" imposed by clonal interference in large populations, and in 2005 another experimental analysis showed that sex speeds up adaptation in yeast but confers no other obvious advantage. Perfeito et al. identified this connection as a major implication of their own work:
...if there is a chance for recombination, clonal interference will be much lower and organisms will adapt faster. [...] Given our results, we anticipate that clonal interference is important in maintaining sexual reproduction in eukaryotes.
(One of the hallmarks of sexual reproduction, besides fun, is recombination – the active shuffling of genetic material that generates offspring with wholly unique mixtures of genes from mom and dad.) In other words, one of the most important benefits of sexual reproduction – and especially of genetic recombination – is negation of the evolutionary drag of clonal interference.

3. All of the examples I've mentioned here are bacterial or viral. If clonal interference arises merely as a result of large population sizes, then it should be an issue for other populations too. And it is: in last month's issue of Nature Genetics, Kao and Sherlock present a tour de force of experimental evolution in a eukaryote, demonstrating the importance of clonal interference and multiple mutations in yeast cells growing asexually. In their study, they identified each beneficial mutation by sequencing the affected gene. Wow.

Why does all of this matter? Well, because it's cool, that's why. And it does mean that our biological enemies have a lot more adaptive resources than we used to think. Here are the closing comments of Perfeito and colleagues:
...our estimate of Ua implies that 1 in 150 newly arising mutations is beneficial and that 1 in 10 fitness-affecting mutations increases the fitness of the individual carrying it. Hence, an enterobacterium has an enormous potential for adaptation and [this] may help explain how antibiotic resistance and virulence evolve so quickly.
But also: keep clonal interference in mind when you encounter any simple story about evolution and genetics. Evolution isn't impossibly difficult to comprehend, but getting it straight requires just a little more effort (and a whole lot more integrity) than has been demonstrated in recent work by those who just can't believe that it could be true.

Article(s) discussed in this post:
L. Perfeito, L. Fernandes, C. Mota, I. Gordo (2007). Adaptive Mutations in Bacteria: High Rate and Small Effects. Science, 317 (5839), 813-815 DOI: 10.1126/science.1142284
K.C. Kao and G. Sherlock (2008). Molecular characterization of clonal interference during adaptive evolution in asexual populations of Saccharomyces cerevisiae. Nature Genetics, 40(12), 1499-1504. DOI: 10.1038/ng.280