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| Lateral Gene Transfer |
Bacteria possess several methods for lateral gene transfer (also called horizontal gene transfer), the transmission of genes between individual cells. These mechanisms not only generate new gene assortments, they also help move genes throughout populations and from species to species. The methods include transformation, transduction, and conjugation.
Transformation involves the uptake of "naked" DNA (DNA not incorporated into structures such as chromosomes) by competent bacterial cells (Fig. 1). Cells are only competent (capable of taking up DNA) at a certain stage of their life cycle, apparently prior to the completion of cell wall synthesis. Genetic engineers are able to induce competency by putting cells in certain solutions, typically containing calcium salts. At the entry site, endonucleases cut the DNA into fragments of 7,000-10,000 nucleotides, and the double-stranded DNA separates into single strands. The single-stranded DNA may recombine with the host's chromosome once inside the cell. This recombination replaces the gene in the host with a variant - albeit homologous - gene. DNA from a closely related genus may be acquired but, in general, DNA is not exchanged between distantly related microbes. Not all bacteria can become competent. While transformation occurs in nature, the extent to which it contributes to genetic diversity is not known.
Transduction is another method for transferring genes from one bacterium to another; this time the transfer is mediated by bacteriophages (bacterial viruses, also called phages) (Fig. 2). A bacteriophage infection starts when the virus injects its DNA into a bacterial cell. The bacteriophage DNA may then direct the synthesis of new viral components assembled in the bacterium. Bacteriophage DNA is replicated and then packaged within the phage particles. Early in the infective cycle the phage encodes an enzyme that degrades the DNA of the host cell. Some of these fragments of bacterial DNA are packaged within the bacteriophage particles, taking the place of phage DNA. The phage can then break open (lyse) the cell. When released from the infected cell, a phage that contains bacterial genes can continue to infect a new bacterial cell, transferring the bacterial genes. Sometimes genes transferred in this manner become integrated into the genome of their new bacterial host by homologous recombination. Such transduced bacteria are not lysed because they do not contain adequate phage DNA for viral synthesis. Transduction occurs in a wide variety of bacteria and is a common mechanism of gene transfer.
Some bacteriophages contribute to the virulence of bacterial infections. Certain phages can enter an alternate life cycle called lysogeny. In this cycle, all the virus's DNA becomes integrated into the genome of the host bacterium. The integrated phage, called a prophage, can confer new properties to the bacterium. For example, strains of Corynebacterium diptheriae, which have undergone lysogenic conversion, synthesize the toxin in diphtheria that damages human cells. Clostridium botulinum and Streptococcus pyogenes, when lysogenized by certain phages, also manufacture toxins responsible for illness, causing botulism and scarlet fever respectively. Strains lacking the prophage do not produce the damaging toxins.
Conjugation is another means of gene transfer in many species of bacteria (Fig. 3). Cell-to-cell contact by a specialized appendage, known as the F-pilus (or sex pilus), allows a copy of an F- (fertility) plasmid to transfer to a cell that does not contain the plasmid. On rare occasions an F-plasmid may become integrated in the chromosome of its bacterial host, generating what is known as an Hfr (high frequency of recombination) cell. Such a cell can also direct the synthesis of a sex pilus. As the chromosome of the Hfr cell replicates it may begin to cross the pilus so that plasmid and chromosomal DNA transfers to the recipient cell. Such DNA may recombine with that of its new host, introducing new gene variants. Plasmids encoding antibiotic-resistance genes are passed throughout populations of bacteria, and between multiple species of bacteria by conjugation.
Lateral gene transfer is a potent evolutionary force that can create diversity within bacterial species (See the Microbial Diversity unit.) As genes for virulence factors and antibiotic resistance spread between and among bacterial populations, scientists are realizing how integral these mechanisms are to the emergence of novel pathogens.