Why uptake sequences matter (up from the data mines)

I've been slaving in the uptake sequence data mines for the past couple of weeks, and although I'm filling the manuscript with new data I'm having a hard time relating this to the big picture. I want to get a draft with all the data to my coauthor on Saturday, because on Sunday I'm off to a meeting.

This is going to be a great meeting because we aren't allowed to use PowerPoint or overheads. In the past we've had 20 minutes and a whiteboard, but this time it's going to be 15 minutes and paper pads so I really need to focus what I'll say. I'm going to talk about uptake sequences, and I'll need to start by explaining why I think they're so important. Here are some steps I could approach it by:

1. Evolvability: One big theme in the study of evolution is whether the processes that generate variation have themselves been subject to natural selection. Have mutation rates been selected to give the best balance between harmful and beneficial changes? Has the genetic code been optimized to minimize the effect of non-silent mutations on fitness? Have developmental processes been selected to channel changes into beneficial directions? Have the genes and sequences that control genetic recombination been selected to optimize the benefits of recombination?

2. Do bacteria have sex? The evolution of sex is a big unsolved problem in eukaryotes. Researchers reasonably assume that sexual reproduction (diploid meiosis + haploid fusion) exists because shuffling alleles into new combinations increases fitness, but they don't have a satisfactory explanation of why this would be true. In bacteria, natural competence (active DNA uptake) is widely assumed to be an analog of meiotic sex, selected because the genetic changes it causes are often beneficial. (At least some researchers accept (if prompted) that other processes that lead to gene transfer do so by accident.)

3. What's the 'null hypothesis'? To study evolutionary function, we need to first think about null hypotheses. If a process has more than one consequence (more than one candidate 'function') we should start by evaluating their likely relative impact. Direct effects on survival are probably more important than evolvability, and inevitable consequences are probably more important than occasional ones. And we need to consider the harmful consequences as well as the beneficial ones. For DNA uptake, the nutrients in DNA are an inevitable benefit to survival, whereas the genetic changes are occasional, indirect, and sometimes good but more often bad

4. The regulation of competence is consistent with selection for nutrients. Are there aspects of the regulation of competence that are consistent with selection for genetic consequences and not for nutrients? Have other consequences for survival been overlooked? Perhaps stalling of replication forks when nucleotide pools are depleted?

5. What about uptake sequences? Two sentence introduction: Two families of bacteria have DNA uptake machineries that prefer short sequences very abundant in their own genomes. This combination of bias and abundance has been assumed to have evolved to optimize the genetic consequences of DNA uptake (to be an adaptation for evolvability).

6. Are uptake sequences evidence of selection for genetic consequences? I've been claiming that, if the DNA uptake machinery has a sequence bias, and if the incoming DNA sometimes recombines with the chromosome, the preferred sequences are expected to accumulate in the chromosome by molecular drive. This is a suitable null hypothesis, as it follows from both the nutrient and evolvability explanations for DNA uptake. It's actually a stronger prediction of the evolvability model, because only that model requires chromosomal recombination. We've now developed a computer-simulation model that lets us test the predictions. If all the properties of real uptake sequences are consistent with accumulation by molecular drive, then there's no need to invoke selection for evolvability.

Oops, I think I've just used up all of my 15 minutes!