Overview
We have discussed how the DNA sequences in cells can be maintained from generation to generation with very little change. However, it is also clear that the DNA sequence in chromosomes does change with time and can, as we discuss in this section, even be rearranged. 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 allow organisms to evolve in response to a changing environment. These DNA rearrangements are caused by a class of mechanisms called genetic recombination.
Homologous Recombination Results in an Exact Exchange of Genetic Information
Of all the recombination mechanisms that exist, perhaps the most fundamental is homologous recombination. The central features that lie at the heart of homologous recombination seem to be the same in all organisms on Earth. Although the mechanism is not completely understood,
the following characteristics are probably common to homologous recombination in all cells:
the following characteristics are probably common to homologous recombination in all cells:
1. Two double-stranded DNA molecules that have regions of very similar (homologous) DNA sequence align so that their homologous sequences are in register. They can then “cross over”: in a complex reaction, both strands of each double helix are broken and the broken ends are rejoined to the ends of the opposite DNA molecule to re-form two intact double helices, each made up of parts of the two different DNA molecules (Figure 6–28).
2. The site of exchange (that is, where a red double helix is joined to a green double helix in Figure 6–28) can occur anywhere in the homologous nucleotide sequences of the two participating DNA molecules.
3. No nucleotide sequences are altered at the site of exchange; the cleavage and rejoining events occur so precisely that not a single nucleotide is lost or gained.
Homologous recombination begins with a bold stroke: a special enzyme simultaneously cuts both strands of the double helix, creating a complete break in the DNA molecule (Figure 6–29). The 5¢ ends at the break are then chewed back by a DNA-digesting enzyme, creating protruding single-stranded 3¢ ends. Each of these single strands then searches for a homologous, complementary DNA helix with which to pair—leading to the formation of a “joint molecule” between the two chromosomes. The nicks in the DNA strands are then sealed so that the two DNA molecules are now held together physically by a crossing-over of one of each of their strands. This crucial intermediate in homologous recombination is known as a cross-strand exchange, or Holliday junction (Figure 6–30).
To regenerate two separate DNA molecules, the two crossing strands must be cut. But if they are cut while the structure is still in the form shown in Figure 6–30A, the two original DNA molecules would separate from each other almost unaltered (Figure 6–30D). The structure can, however, undergo a series of rotational movements so that the two original noncrossing strands become crossing strands and vice versa (Figure 6–30B and C, and Figure 6–31). If the crossing strands are cut after rotation, one section of each original DNA helix is joined to a
section of the other DNA helix; in other words, the two DNA molecules have crossed over, and two molecules of novel DNA sequence have been produced (Figure 6–30E).
section of the other DNA helix; in other words, the two DNA molecules have crossed over, and two molecules of novel DNA sequence have been produced (Figure 6–30E).
As might be expected, cells use a set of specialized proteins to facilitate homologous recombination; these proteins break the DNA, catalyze strand exchange, and cleave Holliday structures. Because the essential features of homologous recombination are highly conserved, the proteins that carry out this process in different organisms are often very similar to one another in amino acid sequence. Homologous recombination provides many advantages to cells and organisms. The process allows an organism to repair DNA that is damaged on both strands of the double helix, and it can fix other genetic accidents that occur during nearly every round of DNA replication. It is also essential for the accurate chromosome segregation that occurs during meiosis in fungi, plants, and animals. The chromosomal “crossing-over” that occurs when homologous chromosomes come together causes bits of genetic information to be exchanged, generating new combinations of DNA sequences in each chromosome. The benefit of such gene mixing for the progeny organisms is apparently so great that the reassortment of genes by homologous recombination is not confined to sexually reproducing organisms; it is also widespread in asexually reproducing organisms, such as bacteria.
Recombination Can Also Occur Between Nonhomologous DNA Sequences
In homologous recombination, DNA rearrangements occur between DNA segments that are very similar in sequence. A second, more specialized type of recombination, called site-specific recombination, allows DNA exchanges to occur between DNA double helices that are dissimilar in nucleotide sequence. Although site-specific recombination performs a variety of tasks in the cell, perhaps its most prevalent function 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. However, most mobile elements can move only within a single cell and its descendants, as they lack any intrinsic ability to leave the cell in which they reside.
Mobile genetic elements often comprise a sizable fraction of an organism’s DNA. For example, approximately 45% of the human genome is made up of mobile genetic elements; most of these elements, however, are fossils that—because they have been accumulating random mutations throughout the course of human evolution—have lost the ability to move within the genome. Because they have a tendency to multiply, mobile DNA elements are sometimes called parasitic DNA. However, mobile genetic elements also provide some advantages to their host genomes by generating the genetic variation upon which evolution depends.
Mobile Genetic Elements Encode the Components They Need for Movement
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 (Figure 6–32). Many elements also carry other genes. For example, viruses encode coat proteins that enable them to exist outside cells, in addition to essential viral enzymes. The spread of mobile genetic elements that carry antibiotic resistance genes is a major factor underlying the widespread dissemination of antibiotic resistance in bacterial populations.
In bacteria, the most common genetic elements are called DNAonly transposons; these generally have only modest selectivity for their target sites and can thus insert themselves into many different DNA sequences. These transposons move from place to place within the genome by means of specialized recombination enzymes, called transposases, that are encoded by the transposable elements themselves (see Figure 6–32). The transposase first disconnects the transposon from the flanking DNA and then inserts it into a new target DNA site. Again, there is no requirement for homology between the ends of the element and the insertion site. Some bacterial transposons move to the target site using a cut-and-paste mechanism; others replicate before inserting into the new chromosomal site, leaving the original copy intact at its previous location (Figure 6–33).
