(Here I'm just trying to lay out the philosophical framework of the Discussion.)
Uptake sequences might seem to be a minor trivial problem (only two relatively unimportant bacterial groups), but they have important implications for the evolution of sex. The key question is, are uptake sequences (= sequence-biased DNA uptake plus abundant preferred sequences in the genome) evidence of selection for benefits of homologous recombination?
Start with recap of what needs to be explained. It's difficult to disentangle the hypotheses: Are bias and accumulation the two interdependent components of an adaptation to promote uptake of fragments that can contribute to beneficial recombination, as often assumed? The big problems with this are the weakness of the hypothesized benefits of recombination in current models of the evolution of sex, and the difficulty of selecting for sequences that only act after the owner is dead. Alternatively, each component (uptake bias and uptake sequences in the genome) could have a separate explanation; for example, uptake sequences might have a cellular function, and sequence bias might play a mechanistic role in uptake.
But an acceptable model for bacterial uptake sequences must explain the very strong correspondence between the sequences that are preferred by the uptake machinery and those that are overrepresented in the genome. Given an abundant sequence with a cellular function, might bias favouring it evolve because of genetic benefits of homologous recombination (mate choice), or because of mechanistic benefits of evolving high-affinity DNA-binding proteins specializing in a commonly available sequence? Conversely, given an intrinsically biased uptake machinery due to mechanistic constraints or the need for high-affinity DNA binding, might the preferred sequences accumulate in the genome regardless of recombination benefits?
This last is the simplest hypothesis to test. Our results show accumulation of uptake sequences like those in real genomes, provided only that DNA uptake is strongly biased and homologous recombination sometimes occurs. The results don't require that the homologous recombination provide any genetic benefits. However, the effects we have found will act regardless of whether the benefit to the cell comes from the DNA's nucleotides or its genetic information. They also don't need selection for homologous recombination, as that occurs anyway in repair-capable cells
So now we have shown that, provided DNA is taken up and bias exists, uptake sequences will accumulate. If DNA uptake is selected because it provides food, then uptake sequences have not evolved as markers of sequence homology, and we expect to find that uptake is biased for non-genetic reasons. If DNA is instead taken up for its genetic information, we need to study how the accumulation of uptake sequences affects the genetic benefits, and how the benefits can affect the evolution of the gene causing the bias..
Our finding that uptake sequences accumulate without selection removes one of the problems with the uptake-bias for sex model (that of needing to simultaneously select for bias and uptake sequences. Instead now just need to test whether uptake bias will evolve (gradually) because of benefits of homologous recombination, with uptake sequence accumulation following passively along. Our model of uptake sequence evolution is not designed to evaluate this because it is not population-based (it tracks only a single focal genome). (Can I mention here my new modeling of the effect of selection at one position?)
An alternative approach is to investigate the role bias plays in the uptake mechanism. Finding that bias is created by a mechanism-independent protein that pre-screens sequences for uptake sequences would support the hypothesis that bias exists to promote homologous recombination. Conversely, finding that bias makes a mechanistic contribution to the process of uptake would be consistent with non-genetic functions of DNA uptake. Our present focus is on properly characterizing the true uptake bias of the H. influenzae uptake system, identifying the gene or genes responsible for the bias, and finding out the role of sequence biases in the mechanism of uptake
19 hours ago in Variety of Life