Mechanisms of DNA uptake are quite conserved (or convergent) but their regulation is complex and very variable. The regulation of competence hasn't been reviewed for about 15 years (Solomon and Grossman 1996, but check for more recent reviews). Much has changed, from microarray studies and followups. Studies of regulation have generally been interpreted in a genetic-consequence framework. We will try to take a broader view, emphasizing the importance of understanding regulation for the ongoing problem of why bacteria take up DNA.
(Also consider who is the intended audience, and how to effectively target them.)
2. Briefly spell out the implications of different kinds of regulation for different ideas about function. (But don't belabor this point - use a light touch here.) If uptake is selected because incoming DNA provides templates for DNA repair, competence should be regulated by the same damage signals that induce recA, or that induce the RecA-regulated SOS response. If uptake is selected because incoming DNA provides nucleotides and other nutrients, competence should be regulated by nucleotide pools and/or by processes that sense availability of sources of C, N and P. If uptake is selected because incoming DNA sometimes carries beneficial new alleles that replace 'inferior' alleles in the chromosome by recombination, then competence should be regulated by ... what? ... I've suggested that competence should be a 'when all else fails' response, induced when the cell's other stress responses have mobilized the relevant genes and expression of these genes has failed to solve the problem. How strictly this test is applied would probably depend on how costly DNA uptake and recombination were, considering both the physiological costs/risks of DNA uptake and the genetic costs of recombining in alleles that reduce fitness.
How have the components of competence regulons been identified? First, genes identified as having roles in transformation (mutant studies), and by specific investigation of regulation. Second, by genome-wide analysis of the genes actived under conditions that cause competence development, both physiological conditions and expression of/dependence on already identified regulators of competence.
What kinds of genes are competence-regulated (under control of competence regulators, bearing in mind that these regulators may not be competence-specific)? We can distinguish between genes that contribute directly to DNA uptake (call these 'competence genes'?), genes affecting what happens to DNA in the cytoplasm (degradation, protection, recombination), and genes with no apparent connection to DNA uptake or transformation. Some of these latter genes have established functions unrelated to DNA uptake, and others have no known function. Some of the genes in all of these categories are also common or ubiquitous in bacteria not known to take up DNA.
For purposes of this review, we will not consider genes that contribute to DNA uptake or transformation but that are not regulated... (maybe have a separate paragraph later?).
In the Discussion (review articles don't have Discussions, this review will have Part I (this introduction), Part II (a survey of all the well-studied organisms), and Part III (pulling-everything together), consider the distinction between how competence develops in lab culture and what might happen under more natural conditions. Does what we know about lab cultures and the regulatory and regulated genes suggest that other factors might be significant regulators in nature?
Detailed outline of Part I:
- Attention-capturing first sentence.
- Competence is the ability to take up DNA. Here we're concerned with 'natural competence'; due to expression of genetically encoded machinery for DNA uptake (distinguish from artificial permeabilization methods).
- Transformation refers to genetic changes that result from recombination of this DNA with the chromosome. This is how competence (and the role of DNA) was discovered, and remains the easiest way to detect DNA uptake. Whether or not transformation results from DNA uptake depends on whether the incoming DNA carries homologous sequences similar enough for recombination, whether it carries different alleles, the extent to which it is degraded during uptake and in the cytoplasm, and the activity of the cellular DNA replication and repair proteins that carry out recombination.
- Competence is widespread but the distribution is locally sporadic. Detecting competence is most easily done by assays of transformation, and transformable bacteria have been found in many families of both gram positive and gram negative bacteria, However, within these families, many species are reported to be not transformable, and the 'transformable' species that have been investigated usually are found to include nontransformable isolates.
- The mechanisms of DNA uptake used by different groups are very similar, with all bacteria transport a single strand of DNA into the cytoplasm with the same inner-membrane channel. Except for Helicobacter and Campylobacter (use family name?), (use ???), all bacteria also use force-generating proteins of the type 4 pili/type II secretion system complex to pull double-stranded DNA to the cytoplasmic/inner membrane.
- Regulation of competence is much more diverse. Different bacteria reported to regulate competence in many different ways (here list some of the extremes). In some cases the regulation appears to be competence-specific, but in others the 'competence' regulons include not only genes that act after DNA has been taken up (affecting its degradation and recombination, but many other genes whose functions appear unrelated to DNA uptake. Another complication is that many bacteria not known to be naturally competent have homologs of genes that are competence-regulated in other bacteria.
- The function of natural competence is controversial, which is one reason for paying close attention to its regulation. Transformation is its most widely known consequence, but DNA from the environment also provides cells with deoxynucleotides that can be recycled for DNA replication or as sources of other nutrients (C, N, P) and with DNA strands that can be used as templates for DNA repair. The genes responsible for the regulation of competence may have evolved to optimize the benefits of DNA uptake (depending on the extent to which the regulation is specific to DNA uptake).
- In this review we will examine the diversity of competence regulation, looking for unifying features, particularly those related to the various benefits DNA uptake can bring. We will also consider how the regulation observed in lab cultures is likely to affect expression of competence in the natural environment.