Why our work is important

On Monday I ran my ideas for my SMBE talk past the postdocs, who politely trashed them. I was making all the errors I know not to make. The worst of these was I wasn't telling the audience why they should care about what I was telling them. One of the reasons I don't worry much about competition is that nobody else is working from the perspective I am, but this means I have to spell out the issues at the start of every talk, starting from the very basics.

The big issue is the evolution of 'sex'. The word sex has lots of meanings; here I mean any biological process that evolved because of the benefits of creating new combinations of genes (new genes or new alleles of genes). (If you've stumbled onto this blog by searching for 'sex' with another meaning in mind, you might want to cut your losses now.) I use this definition because it captures the big unsolved question of why so many eukaryotes engage in 'meiotic sex', that is, they produce a diploid genome by merging two haploid genomes and later produce from this four new haploid genomes with new combinations of genes.

Evolution of sex in eukaryotes is a big issue because we biologists don't know why it's worth the trouble. That sounds feeble, but generations of the best minds have rigorously analyzed the genetic consequences without producing any compelling explanation of why the recombined genomes would be sufficiently better than the original ones to compensate for all the biological costs of sex. The costs aren't such a big deal for facultatively sexual organisms like yeast or paramecium (who can reproduce just fine without meiotic sex), but they're enormous for obligately sexual organisms like ourselves and most other plants and animals, which must use meiotic sex to reproduce.

My approach to this problem is to ask whether bacteria have sex; that is, whether they have any processes that evolved because of benefits of creating new combinations of genes. The key word here is 'because', by which I of course mean 'by natural selection for'. We know that bacteria and archaea have processes that cause recombination, and that these processes have been important in the long-term evolution of their genetic capabilities. But I want to find out whether this happens by accident (as side effects of processes evolved by natural selection for other effects), or by natural selection for the new combinations. If the answer is yes (bacteria do have sex), we'll have shown that this selection is ubiquitous, and we'll have an independent (non-meiotic) system in which to investigate it. If the answer is no, we'll have shown that the reasons for meiotic sex are specific to eukaryotes, and that bacteria get all the genetic recombination they need by accidental effects of other processes.

The reason I have almost no competitors is that researchers have traditionally assumed that the processes that cause genetic recombination in bacteria exist because of selection for such recombination, and very few are willing to seriously consider that this assumption should be rigorously tested. This is a good place for one of my favourite quotations:

"I know that most men, including those at ease with problems of the greatest complexity, can seldom accept even the simplest and most obvious truth if it be such as would oblige them to admit the falsity of conclusions which they have delighted in explaining to colleagues, which they have proudly taught to others, and which they have woven, thread by thread, into the fabric of their lives."

Leo Tolstoy

How are we testing this assumption? By looking for evidence (at the molecular level) of how selection has shaped the processes that cause recombination. There are three such processes, but two of them, conjugation and transduction, can be easily shown to cause recombination only as side effects of genetic parasitism by plasmids and phages respectively. That leaves natural competence (DNA uptake) and its genetic consequence (transformation), which is what we work on. Transformation itself arises when the so-called recombination machinery in the cell acts on DNA the cell has taken up. But this machinery exists not because of selection for making new combinations of genes using DNA brought in from outside, but because of selection for the ability to repair and replicate the cell's own DNA. Because transformation itself is an unselected side effect of the replication and repair machinery, we concentrate on understanding how natural selection has acted on natural competence (the DNA uptake process).

I'll explain how we do this in a later post.