The third main way that bacteria exchange DNA is called DNA transformation. Some bacteria have evolved systems that transport free DNA from the outside of the bacterial cell into the cytoplasm. These bacterial are called "naturally competent" for DNA transformation. Natural DNA transformation of Streptococcus pneumonaiae provided the first proof that DNA encoded the genetic material in experiments by Oswald Avery and colleagues. Some other naturally competent bacteria include Bacillus subtilis, Haemophilus influenzae, and Neisseria gonorrhoeae. Other bacterial species such as E. coli are not naturally competent for DNA transformation. Scientists have devised many ways to physically or chemically force noncompetant bacteria to take up DNA. These methods of artificial DNA transformation form the basis of plasmid cloning in molecular biology.
Most naturally competent bacteria regulate transformation competence so that they only take up DNA into their cells when there is a high density of cells in the environment. The ability to sense how many other cells are in an area is called quorum sensing. Bacteria that are naturally competent for DNA transformation express ten to twenty proteins that form a structure that spans the bacterial cell envelope. In some bacteria this structure also is required to form a particular type of pilus different than the F factor pilus. Other bacteria express similar structures that are involved in secreting proteins into the exterior medium (Type II secretion). Therefore, it appears that DNA transformation and protein secretion have evolved together.
During natural DNA transformation, doubled-stranded DNA is bound to the recipient cell surface by a protein receptor. One strand of the DNA is transported through the cell envelope, where it can recombine with similar sequences present in the recipient cell. If the DNA taken up is not homologous to genes already present in the cell, the DNA is usually broken down and the nucleotides released are used to synthesize new DNA during normal replication. This observation has led to the speculation that DNA transformation competence may have originally evolved to allow the acquisition of nucleic acids for food.
The source of DNA for transformation is thought to be DNA released from other cells in the same population. Most naturally competent bacteria spontaneously break apart by expressing enzymes that break the cell wall. Autolysis will release the genomic DNA into the environment where it will be available for DNA transformation. Of course, this results in the death of some cells in the population, but usually not large numbers of cells. It appears that losing a few cells from the population is counterbalanced by having the possibility of gaining new traits by DNA transformation.