Page 49 - Genetics_From_Genes_to_Genomes_6th_FULL_Part2

208 Chapter 6 DNA Structure, Replication, and Recombination

spores containing one allele, and two spores containing Figure 6.28 How gene conversion occurs. Alleles B and b
the other allele (2:2 segregation)—most of the time. The differ by a single base pair; where B is G–C (yellow), b is T–A (gray).
opportunity to examine all four products of a single meio- If gene B is within the heteroduplex region after a recombination
sis together in an ascus allowed the discovery that rarely, event, repair of mismatched bases may convert B to b or vice versa.
Gene conversion results when the bases changed by DNA repair
tetrads exhibit 3:1 or 1:3 segregation patterns, thereby (black) both originated from the same chromatid. Note that the blue
breaking Mendel’s first law. These rare tetrads are a con- and red lines are single DNA strands.
sequence of heteroduplex formation during recombina- G
tion; the phenomenon that produces these tetrads is called 5' 3'
3' 5'
gene conversion. Allele di erence A
within heteroduplex T
5' 3'
Mismatched bases in heteroduplexes 3' 5'
C
The molecular model for recombination includes formation
of a heteroduplex region, which occurs because the two Mismatch
strands of a recombined DNA molecule do not break and repair
rejoin at the same location on the double helix. In addition, Gene conversion No conversion
through branch migration, the heteroduplex region can be
expanded to hundreds or even thousands of base pairs. The
name heteroduplex applies not only because the two DNA 5' G 5' T 5' G 5' T
strands came from different nonsister chromatids, but also B 3' or b 3' B 3' or b 3'
because the base pairing of the strands may produce mis- C A T C A
G
T
G
matches in which one or a few bases are not complemen- B 5' b 5' b 5' B 5'
tary. If the heteroduplex region is within a gene and the 3' C 3' A 3' A 3' C
maternal and paternal alleles of the gene are different, gene
conversion may result.

Gene conversion through mismatch repair
Mismatched heteroduplex molecules do not persist for that an A B /a b diploid yeast cell, where A and B are linked
long. The same DNA repair enzymes that operate to cor- genes, could produce tetrads of any one of the three types.
rect mismatches during replication (to be discussed in A key feature common to all three of these tetrad types is
Chapter 7) also correct heteroduplexes during recombi- that the ratio of A:a or B:b alleles is always 2:2. However,
nation. The outcome of the repair enzymes’ work de- a rare conversion of b to B results in a tetrad that is neither
pends on which strands they alter. For example, the G–A PD, NPD, nor T, because the ratio of B:b alleles is 3:1
mismatch in Fig. 6.28 can become either G–C or T–A, (Fig. 6.29).
and the T–C mismatch may be repaired to either G–C or The idea that gene conversion is due to heteroduplex for-
T–A (italics indicate the altered base). Therefore, four mation during a recombination event is supported by the
possible repair outcomes exist for the two mismatches observation that gene conversion is often associated with
generated at a heteroduplex. Two of those outcomes— crossing-over of flanking alleles. For example, suppose
those in which both heteroduplexes are repaired to gen- during meiosis in an A B C / a b c diploid yeast, a recombi-
erate the same base pair—may result in gene conversion. nation event occurs between gene A and gene C such that
Suppose that, as in Fig. 6.28, the base pair difference gene B is within the heteroduplex region (Fig. 6.29). Reso-
within a heteroduplex is the molecular difference be- lution of Holliday junctions on either side of gene B results
tween two alleles B and b. One nonsister chromatid in crossing-over—recombination between alleles of the
started out with B and the other with b. The result of flanking genes A and C. Subsequent DNA repair of the
gene conversion is that both chromatids end up with the heteroduplex regions containing gene B can result in gene
same allele—both are either B or b. conversion, producing a tetrad that displays 3:1 segregation
of B:b or b:B (Fig. 6.29a).
You should note that heteroduplexes resulting from
Gene conversion in yeast and Neurospora asci recombination events that enter the noncrossover path-
Gene conversion is noticeable in yeast and Neurospora be- way can also generate tetrads with 3:1 segregation pat-
cause all of the products of a single meiosis stay together in terns. In such cases, gene conversion occurs but is not
an ascus. Gene conversion may be detected as an unusual accompanied by recombination of the alleles of the
ascus that is neither PD, NPD, nor T. Recall from Fig. 5.22 flanking genes (Fig. 6.29b).