How does the cell decide which Spo11-induced double-strand breaks to resolve as crossovers? The answer is not yet known, but we know the decision is an important one. The relatively few crossovers that do form are distributed along chromosomes in such a way that a crossover in one position inhibits crossing-over in neighboring regions. Termed crossover control, this fascinating but poorly understood regulatory mechanism ensures the roughly even distribution of crossover points along chromosomes. It also ensures that each chromosome— no matter how small—undergoes at least one crossover every meiosis. For many organisms, roughly two crossovers per chromosome occur during each meiosis, one on each arm. As discussed in detail in Chapter 17, these crossovers play an important mechanical role in the proper segregation of chromosomes during meiosis.
Whether a meiotic recombination event is resolved as a crossover or a non-crossover, the recombination machinery leaves behind a heteroduplex region where a strand with the DNA sequence of the paternal homolog is base-paired with a strand from the maternal homolog (Figure 5–58). These heteroduplex regions can tolerate a small percentage of mismatched base pairs, and because of branch migration, they often extend for thousands of nucleotide pairs. The many non-crossover events that occur in meiosis thereby produce scattered sites in the germ cells where short DNA sequences from one homolog have been pasted into the other homolog. Heteroduplex regions mark sites of potential gene conversion—where the four haploid chromosomes produced by meiosis contain three copies of a DNA sequence from one homolog and only one copy of this sequence from the other homolog (see Figure 5–53), as explained next.
Figure 5–58 Heteroduplexes formed during meiosis. Heteroduplex DNA is present at sites of recombination that are resolved either as crossovers or non-crossovers. Because the DNA sequences of maternal and paternal chromosomes differ at many positions along their lengths, heteroduplexes often contain a small number of base-pair mismatches.
Figure 5–59 Gene conversion caused by mismatch correction. In this process, heteroduplex DNA is formed at the sites of homologous recombination between maternal and paternal chromosomes. If the maternal and paternal DNA sequences are slightly different, the heteroduplex region will include some mismatched base pairs, which may then be corrected by the DNA mismatch repair machinery (see Figure 5–19). Such repair can “erase” nucleotide sequences on either the paternal or the maternal strand. The consequence of this mismatch repair is gene conversion, detected as a deviation from the segregation of equal copies of maternal and paternal alleles that normally occurs in meiosis.
In sexually reproducing organisms, it is a fundamental law of genetics that—aside from mitochondrial DNA, which is inherited only through the mother—each parent makes an equal genetic contribution to an offspring. One complete set of nuclear genes is inherited from the father and one complete set is inherited from the mother. Underlying this law is the accurate parceling out of chromosomes to the germ cells (eggs and sperm) that takes place during meiosis. Thus, when a diploid cell in a parent undergoes meiosis to produce four haploid germ cells, exactly half of the genes distributed among these four cells should be maternal (genes inherited from the mother of this parent) and the other half paternal (genes inherited from the father of this parent). In some organisms (fungi, for example), it is possible to recover and analyze all four of the haploid gametes produced from a single cell by meiosis. Studies in such organisms have revealed rare cases in which the parceling out of genes violates the standard genetic rules. Occasionally, for example, meiosis yields three copies of the maternal version of a gene and only one copy of the paternal allele. Alternative versions of the same gene are called alleles, and it is the divergence from their expected distribution during meiosis that is known as gene conversion. Genetic studies show that only small sections of DNA typically undergo gene conversion, and in many cases only a part of a gene is changed.