Page 155 - Genetics_From_Genes_to_Genomes_6th_FULL_Part1

5.3 Mapping: Locating Genes Along a Chromosome 147

double-crossover progeny are the rarest by looking at the Interference is not uniform and may vary even for dif-
probability of their occurrence. If an exchange in region 1 ferent regions of the same chromosome. Investigators can
of a chromosome does not affect the probability of an ex- obtain a quantitative measure of the amount of interference
change in region 2, the probability that both will occur si- in different chromosomal intervals by first calculating a
multaneously is the product of their separate probabilities coefficient of coincidence, defined as the ratio between
(recall the product rule in Chapter 2). For example, if prog- the actual frequency of double crossovers observed in an
eny resulting from recombination in region 1 alone account experiment and the number of double crossovers expected
for 10% of the total progeny (that is, if region 1 is 10 m.u.) on the basis of independent probabilities.
and progeny resulting from recombination in region 2 alone frequency observed
account for 20%, then the probability of a double crossover coefficient of coincidence =
(one event in region 1, the second in region 2) is 0.10 × frequency expected
0.20 = 0.02, or 2%. This makes sense because the likeli- For the three-point cross involving vg, pr, and b, the coef-
hood of two rare events occurring simultaneously is even ficient of coincidence is
smaller than that of either rare event occurring alone.
If eight classes of progeny are obtained in a three-point 0.52 = 0.66.
cross, the two classes containing the fewest progeny must 0.79
have arisen from double crossovers. The numerical fre-
quencies of observed double crossovers, however, almost The definition of interference itself is
never coincide with expectations derived from the product Interference = 1 − coefficient of coincidence.
rule. Let’s look at the actual numbers from the cross we
have been discussing. The probability of a single crossover In this case, the interference is
between vg and pr is 0.123 (corresponding to 12.3 m.u.), 1 − 0.66 = 0.34.
and the probability of a single crossover between pr and b
is 0.064 (6.4 m.u.). The product of these probabilities is To understand the meaning of interference, it is helpful
to contrast what happens when there is no interference with
0.123 × 0.064 = 0.0079 = 0.79%. what happens when interference is complete. If interfer-
But the observed proportion of double crossovers (see ence is 0, the frequency of observed double crossovers
Fig. 5.11) was equals expectations, and crossovers in adjacent regions of a
chromosome occur independently of each other. If interfer-
13 + 9 × 100 = 0.52%. ence is complete (that is, if interference = 1), no double
4197 crossovers occur in the experimental progeny because one
The fact that the number of observed double cross- exchange effectively prevents another. As an example, in a
overs is less than the number expected if the two exchanges particular three-point cross in mice, the recombination fre-
are independent events suggests that the occurrence of one quency for the pair of genes on the left (region 1) is 20, and
crossover reduces the likelihood that another crossover for the pair of genes on the right (region 2), it is also 20.
will occur in an adjacent part of the chromosome. This Without interference, the expected rate of double cross-
phenomenon—of crossovers not occurring independently— overs in this chromosomal interval is
is called chromosomal interference. 0.20 × 0.20 = 0.04 , or 4%,
As was shown in Fig. 5.7, interference likely exists to
ensure that every pair of homologous chromosomes under- but when investigators observed 1000 progeny of this cross,
goes at least one crossover. It is crucial that every pair of they found 0 double recombinants instead of the expected 40.
homologous chromosomes sustain one or more crossovers
because such events help the chromosomes orient properly A method to determine the gene in the middle
at the metaphase plate during the first meiotic division. The smallest of the eight possible classes of progeny in a
Indeed, homologous chromosome pairs without crossovers three-point cross are the two that contain double recombi-
often segregate improperly. If only a limited number of nants generated by double crossovers. It is possible to use
crossovers can occur during each meiosis, and interference the composition of alleles in these double crossover classes
lowers the number of crossovers on large chromosomes, to determine which of the three genes lies in the middle,
then the remaining possible crossovers are more likely to even without calculating any recombination frequencies.
occur on small chromosomes. This increases the probabil- Consider again the progeny of a three-point testcross
ity that at least one crossover will take place on every ho- looking at the vg, pr, and b genes. The F 1 females are vg pr
+
+
+
mologous pair. Though the molecular mechanism b / vg pr b . As Fig. 5.14d demonstrated, testcross prog-
underlying interference is not yet clear, recent experiments eny resulting from double crossovers in the trihybrid fe-
suggest that interference is mediated by the synaptonemal males of the F 1 generation received gametes from their
+
+
complex. mothers carrying the allelic combinations vg pr b and vg