Sunday, October 28, 2007

Hooray for Mutation

I've always tried to cover the most up-to-date research in my journal club series, but today's paper is an exception. "Strong Selective Sweep Associated with a Transposon Insertion in Drosophila simulans" was published in 2004, and I actually covered it for my old lab's journal club when it first came out.

So why am I coming back to this research now?

The answer is that Todd Schlenke and David Begun's paper is a fantastic illustration of positive selective pressure acting on a beneficial mutation. It is therefore extremely useful when debating creationists, as I found out in the extended comments thread on an older post. (For some reason, fruit fly genetics papers often make good rebuttals to creationist thinking.) Some creationists claim that mutations are always harmful and therefore can't be used as the basis of natural selection and evolution. They believe that the likelihood of a mutation being beneficial to the organism is practically nil, and that species therefore did not evolve but had to be designed. The evolutionary model proposes that beneficial mutations are indeed rare, but are powerful drivers of natural selection when they do occur.

Are you positive there was selection?

The "selective sweep" of the paper's title refers to rapid positive selection of a beneficial mutation. That means that the mutation conferred a strong enough advantage that the mutant fly and its offspring reproduced much more successfully than other flies, and the original mutation quickly became the population's new "normal" sequence. When a mutation spreads rapidly, there is not enough time for the mutated chromosome to exchange segments with its sister, normal, chromosome1, and a block of the original fly's DNA surrounding the mutation is passed down to all offspring more or less intact.

It is possible to scan the DNA of different members of the same population for blocks of chromosome that show no sign of crossing over. Schlenke and Begun, who are based at the University of California, Davis, performed just such a scan with local fruit flies of the D. simulans species. They found a large chromosomal segment with no evidence of chromosomal exchange on which to focus their studies.

Time flies like an arrow, fruit flies like a mutated regulatory region

There are 22 different genes in the region of interest, and one of them looked particularly interesting. Cyp6g1 codes for a protein that is involved in detoxifying various chemicals, including insecticides. It also has a transposable element (similar to an endogenous retrovirus) inserted in its transcriptional regulatory region. The element is almost identical to the standard sequence for its family, which indicates that it hopped into position recently enough not to have accumulated many mutations. 98% of the flies caught in California possessed the exact same insertion. So this is a recent mutation that has spread extremely rapidly to become the new normal sequence in this particular population. What an excellent candidate for the cause of the selective sweep in this region of the genome.

But what does the insertion do? It must have something to do with the expression of the Cyp6g1 gene, right? Right. Flies with the transposable element expressed higher levels of the detoxifying gene than flies without the mutation, and were slightly more resistant to the notorious DDT insecticide. Another example of the potential evolutionary impact of changes to the regulation of gene expression.

Under pressure

A beneficial mutation will not spread rapidly unless there is some kind of selective pressure acting on it. In this case, the pressure was probably exposure to a toxic chemical of some kind, rendering an increase in Cyp6g1 expression much more useful than it would have been in a less toxic environment. DDT was used extensively in California between 1945 and 1972, but the slight increase in DDT resistance in the mutated flies does not appear to provide enough of an advantage to explain the speed of the selective sweep. In addition, the frequency of the mutation would most likely have fallen in the last 35 years once DDT was removed from the environment. Cyp6g1 provides protection from a range of chemicals, and it is likely that something other than DDT was responsible for the initial rapid spread of the transposable element insertion, and is now responsible for maintaining the high frequency of the insertion in the population.

The proof of the pudding...

The importance of a research paper can be inferred from the number of times it is cited by other authors. The Schlenke-Begun study has been cited an impressive 54 times to date2, by authors who have found their own examples of selective sweeps as well as those who are interested in transposable elements or pesticide resistance. So this paper stands out not just because it's a neat scientific story that beautifully illustrates a key point in evolutionary theory, but also because of its cross-disciplinary impact on multiple fields of research.

Beat that, creationists!

1This process, known as crossing over, occurs between pairs of identical chromosomes as the sperm or egg cells are produced. Recombination ensures that the chromosome sets you inherited from your mother and from your father are not passed down intact to your own children, but instead swap segments between the two sets to create a unique chromosome sequence in each new individual.

2Bastards. Yes I'm


  1. so,... any day now we should be seeing fruit flys turning into birds.... I am not holding my breath.

  2. Yes, because obviously the theory of evolution predicts that insects will turn into birds, zebras and crocodiles all the time.


    Please read this and have a look at the List of Claims.

    Fruit flies will remain fruit flies, but they will evolve new features such as increased insecticide resistance given the right combination of mutation and selective pressure. That's pretty cool, yeah?

  3. Their brand new paper just got published today on PLoS ONE:

    Take a look. Let me know if you want to do a REAL journal club on it.

    Bora Zivkovic
    PLoS online community Manager

  4. Nice timing for this post then - complete coincidence!

    The new paper has too many stats and too little molecular biology for me to be able to offer much in the way of informed comment though. I never could get my head around stats properly.

    Do you guys have an actual journal club feature, or are you looking more for comments on published articles?


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