Framing the uptake sequence problem (Intro and Discussion)

I think the last post may have been a bit incoherent, but it led me to a new perspective on the problems posed by uptake sequences, one that I think gives a much better frame for the manuscript.

INTRODUCTION (new frame):

(After introducing uptake sequences and uptake biases...)

Why bacteria take up DNA is controversial, and presence in two bacterial groups of DNA uptake sequences and their associated uptake biases pose problems for both major hypotheses.

It's generally assumed that bacteria take up DNA to get benefits from homologous genetic recombination, and that uptake sequences plus biases are a mate-choice adaptation to maximize these benefits by excluding DNAs that are not from close relatives.  Although this is intuitively appealing, it is evolutionarily problematic, both because it requires simultaneous evolution of bias in the uptake machinery and genomic sequences matching this bias, and because the genomic sequences can only be 'selected' after the cell carrying them is dead.  (There's also the bigger problem that the presumed benefits of recombination are expected to be, on average, very small or nonexistent.)

The alternative hypothesis is that bacteria take up DNA as a source of nutrients (initially nucleotides but also carbon, nitrogen and phosphate), for which the very existence of uptake sequences plus bias is counterintuitive.  If DNA in the environment is valued only as nucleotides on a string, all DNAs should be equally useful.  Although the sequence bias might play a mechanistic role in DNA uptake (such biases are typical of proteins that bind DNA, even ones whose functions are sequence independent), the high density of the preferred sequences in the genome is perplexing.

The phenomenon of molecular drive may resolve the worst of these problems for both hypotheses, by providing a hypothesis-neutral explanation for uptake sequence abundance.

(Explain molecular drive here.)

If molecular drive is indeed an inevitable consequence of biased DNA uptake and homologous recombination, its action may remove the biggest obstacles for both hypotheses.  Below we use a computer simulation of genome evolution to test its requirements and consequences.

METHODS

RESULTS

DISCUSSION (new frame):


Summarize the findings.  They are robust.

What's been gained:  Proponents of the mate-choice hypothesis now need only explain how natural selection for the benefits of recombination would favour uptake specificity in the genes encoding the uptake machinery - the corresponding uptake sequences will inevitably accumulate in the genome as the specificity strengthens.  Proponents of the DNA=food hypothesis need only explain how sequence bias would evolve for mechanistic benefits in DNA uptake; uptake sequences in the genome can be ignored.

The above paragraph is really too adversarial a perspective.  It's now much clearer what information is needed to explain uptake specificity.  First we need a much more detailed characterization of the real uptake biases (Neisserial and Pasteurellacean).  Second we need to know what role uptake bias plays in the process of uptake in each organism.  Does a dedicated cell-surface protein pre-screen DNA fragments for uptake sequences before uptake is initiated?  Do uptake sequences provide structural flexibility for DNA bending or kinking during initiation of uptake?  Do uptake sequences play any role after initiation?  Do they affect DNA synapsis or other stages of recombination?

We also need new explicit models of the evolutionary forces that would act on uptake genes and preferred sequences.  Can selection for genetic benefits of recombination be strong enough to cause evolution of uptake bias?  Or, vice versa, can exclusion of unrelated DNAs reduce the costs of DNA uptake?  Analysis of protein sequences in genomes with and without uptake sequences suggests that their evolutionary costs are small, but a theoretical framework for this is lacking.  Because the model presented in this paper tracks only a single focal genome, it is not suitable for investigating effects on organismal fitness (whether due to the costs of uptake sequences or to the genetic benefits of recombination).