Revising the USS manuscript

Our manuscript about the within-genome diversity of uptake signal sequences (USSs) and their effect on DNA uptake was provisionally accepted, but we need to do substantial revisions to satisfy the reviewers, especially as we really don't want to have to do more experiments for this manuscript. On rereading the Introduction, I realized that changing the perspective might be good.

In the present version of the Introduction we do the following (each point is a paragraph):

1. Introduce natural competence.
2. Describe the general process of DNA uptake.
3. Explain that H. influenzae and Neisseria preferentially take up DNA fragments with specific sequences.
   
4. Describe how the H. influenzae uptake specificity was determined.
5. Describe how the USSs in the H. influenzae genome were characterized once the genome sequence became available in 1995.
6. Describe the USSs in the genome and possible non-uptake functions for these USSs.
7. Describe the distribution of USSs in the genomes of related bacteria.
8. Say that USSs arise by point mutation (not insertion) and that molecular drive can explain their accumulation in the genome.
9. Provide a mechanistic explanation of why the DNA uptake machinery might be biased towards a specific sequence.
   
10. Explain why we need a better understanding of the USS motif and the specificity of the uptake machinery.
11. Summarize the results that the manuscript presents.

My alternative perspective would frame the results in the context of repeated sequence evolution rather than of competence. It would go as follows:

1. All genomes contain repeats, which usually fall into one of three kinds: dispersed multi-copy elements that spread by copying and insertion (selfish DNA); motifs that arise by point mutation and interact with specific cellular DNA-binding proteins (e.g. binding sites for transcription factors); and simple-sequence repeats that in bacteria arise by polymerase slipping and function to promote gene activation/inactivation by frameshifting. This paper is about an abundant repeat that doesn't fit any of these.
   
2. These repeats are called uptake signal sequences. Describe what's known about length, copy number, consensus, distribution in genome and between species. How we know they are motifs and not insertions.
   
3. Possible within-cell functions and relevant information from bioinformatics.
4. Occur only in a few naturally competent bacteria. Discovered because are preferred by uptake machinery. Similarity between preferred sequence and genome abundance can't be coincidental.
   
5. Describe competence. Usual explanation for USS is selection as mate-choice marker. Why this is problematic.
6. Describe alternative explanation = molecular drive: USSs accumulate as a side effect of uptake bias and recombination.
7. Provide a mechanistic explanation of why the DNA uptake machinery might be biased towards a specific sequence.
   
8. Explain why we need a better understanding of the USS motif and the specificity of the uptake machinery. Focus on molecular drive as an important phenomenon in its own right, as well as on why cells take up DNA.
   
9. Summarize the results that the manuscript presents.

I think this might be a better outline - appealing more broadly to people interested in genome evolution as well as to those interested in competence. But I wonder if it's worth making this big a change to the manuscript at this stage.