Natural competence

In microbiology, genetics, cell biology, and molecular biology, competence is the ability of a cell to alter its genetics by taking up extracellular ('naked') DNA from its environment in the process called transformation. Competence may be differentiated between natural competence, a genetically specified ability of bacteria which is thought to occur under natural conditions as well as in the laboratory, and induced or artificial competence, which arises when cells in laboratory cultures are treated to make them transiently permeable to DNA. Competence allows for rapid adaptation and DNA repair of the cell. This article primarily deals with natural competence in bacteria, although information about artificial competence is also provided. In microbiology, genetics, cell biology, and molecular biology, competence is the ability of a cell to alter its genetics by taking up extracellular ('naked') DNA from its environment in the process called transformation. Competence may be differentiated between natural competence, a genetically specified ability of bacteria which is thought to occur under natural conditions as well as in the laboratory, and induced or artificial competence, which arises when cells in laboratory cultures are treated to make them transiently permeable to DNA. Competence allows for rapid adaptation and DNA repair of the cell. This article primarily deals with natural competence in bacteria, although information about artificial competence is also provided. Natural competence was discovered by Frederick Griffith in 1928, when he showed that a preparation of killed cells of a pathogenic bacterium contained something that could transform related non-pathogenic cells into the pathogenic type. In 1944 Oswald Avery, Colin MacLeod, and Maclyn McCarty demonstrated that this 'transforming factor' was pure DNA . This was the first compelling evidence that DNA carries the genetic information of the cell. Since then, natural competence has been studied in a number of different bacteria, particularly Bacillus subtilis, Streptococcus pneumoniae (Griffith's 'pneumococcus'), Neisseria gonorrhoeae and Haemophilus influenzae. Areas of active research include the mechanisms of DNA transport, the regulation of competence in different bacteria, and the evolutionary function of competence. In the natural world DNA usually becomes available by death and lysis of other cells, but in the laboratory it is provided by the researcher, often as a genetically engineered fragment or plasmid. During uptake, DNA is transported across the cell membrane(s), and the cell wall if one is present. Once the DNA is inside the cell it may be degraded to nucleotides, which are reused for DNA replication and other metabolic functions. Alternatively it may be recombined into the cell's genome by its DNA repair enzymes. If this recombination changes the cell's genotype the cell is said to have been transformed. Artificial competence and transformation are used as research tools in many organisms (see Transformation (genetics)). In almost all naturally competent bacteria components of extracellular filaments called type 4 pili (a type of fimbria) bind extracellular double stranded DNA. The DNA is then translocated across the membrane (or membranes for gram negative bacteria) through multi-component protein complexes driven by the degradation of one strand of the DNA. Single stranded DNA in the cell is bound by a well-conserved protein, DprA, which loads the DNA onto RecA, which mediates homologous recombination through the classic DNA repair pathway. In laboratory cultures, natural competence is usually tightly regulated and often triggered by nutritional shortages or adverse conditions. However the specific inducing signals and regulatory machinery are much more variable than the uptake machinery, and little is known about the regulation of competence in the natural environments of these bacteria. Transcription factors have been discovered which regulate competence; an example is sxy (also known as tfoX) which has been found to be regulated in turn by a 5' non-coding RNA element. In bacteria capable of forming spores, conditions inducing sporulation often overlap with those inducing competence. Thus cultures or colonies containing sporulating cells often also contain competent cells. Recent research by Süel et al. has identified an excitable core module of genes which can explain entry into and exit from competence when cellular noise is taken into account. Most competent bacteria are thought to take up all DNA molecules with roughly equal efficiencies, but bacteria in the families Neisseriaceae and Pasteurellaceae preferentially take up DNA fragments containing short DNA sequences, termed DNA uptake sequence (DUS) in Neisseriaceae and uptake signal sequence (USS) in Pasteurellaceae, that are very frequent in their own genomes. Neisserial genomes contain thousands of copies of the preferred sequence GCCGTCTGAA, and Pasteurellacean genomes contain either AAGTGCGGT or ACAAGCGGT. Most proposals made for the primary evolutionary function of natural competence as a part of natural bacterial transformation fall into three categories: (1) the selective advantage of genetic diversity; (2) DNA uptake as a source of nucleotides (DNA as “food”); and (3) the selective advantage of a new strand of DNA to promote homologous recombinational repair of damaged DNA (DNA repair). A secondary suggestion has also been made, noting the occasional advantage of horizontal gene transfer. Arguments to support genetic diversity as the primary evolutionary function of sex (including bacterial transformation) are given by Barton and Charleworth . and by Otto and Gerstein. However, the theoretical difficulties associated with the evolution of sex suggest that sex for genetic diversity is problematic. Specifically with respect to bacterial transformation, competence requires the high cost of a global protein synthesis switch, with, for example, more than 16 genes that are switched on only during competence of Streptococcus pneumoniae. However, since bacteria tend to grow in clones, the DNA available for transformation would generally have the same genotype as that of the recipient cells. Thus, there is always a high cost in protein expression without, in general, an increase in diversity. Other differences between competence and sex have been considered in models of the evolution of genes causing competence; these models found that competence's postulated recombinational benefits were even more elusive than those of sex.