DNA Recombination

DNA Recombination

The particular combination of genes present in any individual genome is often altered by such DNA rearrangements. In a population, this sort of genetic variation is important to in order to allow organisms to evolve in response to a changing environment. These DNA rearrangements are caused by a class of mechanisms called genetic recombination.

DNA recombination can be

Homologous    Homologous recombination takes place between DNA molecules with similar nucleotide sequences. The breaking and rejoining of two homologous DNA double helices creates two DNA molecules which have “crossed over.” (exchanged strands)Although the two original DNA molecules must have similar nucleotide sequences in order to cross over, they do not have to be identical; thus a crossover can create DNA molecules of novel nucleotide sequence. Homologous recombination begins with a doublestrand break in a chromosome. A DNA-digesting enzyme then creates protruding 3' ends, which find the homologous region of a second chromosome. The joint molecule formed can eventually be resolved by selective strand cuts to produce two chromosomes that have crossed over.

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Another more specialized type of recombination, called site-specific recombination, allows DNA exchanges to occur between DNA double helices that are dissimilar in nucleotide sequence.

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The most likely fuction of this type of recombination process is to shuffle specialized bits of DNA called mobile genetic elements. These elements, found in the genomes of nearly all organisms, are short sequences of DNA that can move from one position in the

genome to another through site-specific recombination. Some of these mobile genetic elements are viruses that take advantage of site-directed recombination to move their genomes into and out of the chromosomes of their host cell. A virus can package its nucleic acid into viral particles that can move from one cell to another through

the extracellular environment. Unlike homologous recombination, site-specific recombination is guided by recombination enzymes that recognize short, specific nucleotide sequences present on one or both of the recombining DNA molecules; extensive DNA homology is not required. Each type of mobile genetic element generally encodes the enzyme that mediates its own movement and contains special sites upon which the enzyme acts. Bacteria contain many types of mobile genetic elements called transposons.  Each of these DNA

transposons contains a gene that encodes a transposase , an enzyme that carries out some of the DNA breaking and joining reactions needed for the transposon to move. Each transposon also carries DNA sequences that are recognized only by the transposase encoded by that element and are necessary for movement of the transposon. Some transposons carry, in addition, genes that encode enzymes that inactivate antibiotics such as ampicillin (ampR) and tetracycline (tetR). Movement of these genes presents a growing problem in medicine, as many disease-causing bacteria have become resistant to many of the antibiotics developed during the twentieth century.

Although there are many similarities between bacterial and eukaryotic viruses, one important type of virus (retrovirus) is found only in eucaryotic cells. Retroviruses resemble the retrotransposons which are transposons that synthesize DNA using RNA as a template (the term “retro” refers to this backward flow of the central dogma). The enzyme that carries out this step is reverse transcriptase; the retroviral genome (which is single-stranded RNA) encodes this enzyme.

The life cycle of a retrovirus.

The retrovirus genome consists of an RNA molecule of about 8500 nucleotides; two such molecules are packaged into each viral particle. The enzyme reverse transcriptase first makes a DNA copy of the viral RNA molecule and then a second DNA strand, generating a double-stranded DNA copy of the RNA genome. The integration of this DNA double helix into the host chromosome is then catalyzed by a virus-encoded integrase enzyme. This integration is required for the synthesis of new viral RNA molecules by the host cell RNA polymerase, the enzyme that transcribes DNA into RNA.