I. Haldane's rule
A. Statement of Haldane's rule: When in the F offspring produced
by crossing two taxa, one sex is absent,
rare or sterile, that sex is the heterogametic sex.
1. In organisms with X-Y sex determination (e.g. Drosophila, mammals),
males are the hetergametic
sex (i.e. males are XY, females are XX).
2. Consequently, Haldane's rule states that in these organisms, whenever
there is partial reproductive
isolation, males should exhibit reduced viability or sterility more so than
females.
3. By contrast, in organisms with Z-W sex determination (e.g. birds,
butterflies), females are the
heterogametic sex (i.e. males are ZZ, females are ZW).
4. Haldane's rule states that in these organisms, whenever there is
partial reproductive isolation,
females should exhibit reduced viability or sterility more so than males.
B. Evidence
1. A recent compendium of several hundred
cases of sex-specific reproductive isolation indicates that
in most cases, Haldane's rule is obeyed.
2. The near universality of this phenomenon indicates that it is one
of the most robust generalizations
in evolutionary biology.
1. As the figure shows, hybrids obtain one copy of each chromosome
from each parental species.
3. However, by crosses, one can make males that that carry all chromosomes
from one species,
but a Y-chromosome from the other species:
4. Consequently, it does not appear that the presence of incompatibility
alleles on the Y chromosome
can be a general explanation for Haldane's rule.
III. Explaining Haldane's rule: Muller's X-Autosome imbalance theory ("dominance theory")
A. Explanation of theory
1. Suppose genetic incompatibility between two species, with genotypes
AAbb and aaBB
respectively, results from alleles A and B being combined in hybrids (i.e.
A and B together
is detrimental.)
2. This effect by itself will not produce hybrid inviability or sterility
that is confined to just the
heterogametic sex.
3. However, let us further assume that the detrimental A-B interaction
is buffered by the presence
of a and b alleles, so that in the heterozygote AaBb, the detrimental
interaction is recessive and
not expressed.
4. In this case, if both A and B are on autosomes, then both
sexes will be buffered and neither sex
will exhibit hybrid inviability or sterility.
5. However, if one gene, say A, is on the X chromosome, the result is more interesting.
a. Female hybrids are AaBb, the A-B interaction is buffered, and females
exhibit no
detrimental effects.
b. By contrast, male hybrids are AYBb (Y chromosomes are essentially
devoid of genes).
c. At the A locus, male hybrids are "hemizygous" they contain only
one copy of the A gene.
d. There is thus no a allele to provide an a-b interaction to buffer
the A-B interaction and
males are thus inviable or sterile.
6. Thus, according to Muller's hypothesis, recessive incompatibility
alleles accumulate on all
chromosomes.
a. Given recessivity of detrimental interactions, pairs of incompatibility
alleles that are
both on autosomes do not contribute to hybrid inviability or infertility.
b. But pairs of alleles in which at least one locus is on the X chromosome
will contribute
to hybrid inviability/sterility in males but not in females.
7. This effect depends on incompatibility alleles being on average
recessive--it has been shown
theoretically that if such alleles are dominant on average, then hybrid inviability/sterility
will
tend to occur in females rather than males.
8. There is no reason to expect incompatibility alleles to be recessive
on average, but we can't rule
out this possibility either. Whether Muller's hypothesis is correct
is thus an empirical matter
open to experiment.
B. Experimental test of Muller's hypothesis--rationale
1. If hybrid breakdown is stronger in the heterogametic sex (males)
because there isn't a sex
chromosome carrying an allele to buffer the A-B interaction, then one should
see similar
breakdown in females in which there isn't a buffering allele.
2. To create such females, use attached-X chromosome: two X-chromosomes
that are connected and
segregate together at meiosis.
3. The cross that is done, then is
AAbb female x a-BB male
Using Normal female:
XAXA bb x XaY BB => XAXaBb female: viable and fertile
XAY Bb male: inviable or sterile
Using Attached-X female:
XA--XAYbb x
XaY BB =>
XA--XAXa Bb dies (too
many X's)
XA--XA Y Bb female (2 X's)
4. If Muller's hypothesis is correct, then the XA--XA
YBb females should also be inviable or sterile
because they carry an A-B interaction that is not buffered by an a.
C. Experimental test of Muller's hypothesis--results.
(From, C. C. Laurie. 1997.
The weaker sex is
heterogametic:
75 years of Haldane's rule.
Genetics 147:
937-951.)
1. Two sets of crosses (D. melanogaster female x D. simulans
or D.mauritiana male, and
D. simulans female x D. teissieri male) are consistent with
Muller's explanation in that
the attached-X females are inviable, just as are the regular hybrid males.
2. However, a cross between D.simulans female and D. mauritiana
or D. sechellia male does not
support Muller's explanation because the attached-X females are viable and
fertile, while
the normal hybrid males are sterile.
3. One possible explanation for these different results arises from
the recognition that in the
two cases supporting Muller's explanation, hybrid males were inviable, whereas
in the one case
that does not support explanation, hybrid males were viable but infertile.
4. The data thus suggests that Muller's explanation may hold for sex-limited
hybrid inviability,
but not for sex-limited hybrid sterility.
5. This makes sense.
a. Viability tends to be affected by the same genes in males and females.
Consequently,
any incompatibility genes on the X chromosome that are expressed in hybrid
males and
cause inviability will also be expressed in hybrid attached-X females and
cause inviability:
c. In such a situation, Haldane's rule would hold, but the attached-X
test of Muller's
explanation would fail. (see Figure)
a. Incompatibility genes affecting male fertility may accumulate more
quickly on all
chromosomes than inc. genes affecting female fertility.
--One possible reason is that male traits evolve faster due to sexual selection.
b. Such genes affecting male fertility may accumulate more rapidly
than those affecting
female sterility on X chromosome alone, accumulating at similar rates on
autosomes.
--See below for explanation.
IV. Explaining Haldane's rule for fertility: differential accumulation theory
A. Experimental method
1. General rationale:
a. introgress small pieces of single chromosomes into the genome
of another species
b. determine, for each piece, whether it carries incompatibility alleles
affecting male
fertility, female fertility, or both.
c. If there are more pieces that affect male fertility, implies alleles
affecting male fertility
accumulate (evolve) more rapidly than alleles affecting female fertility.
2. Procedure: Backcross
a. Insert a small gene segment carrying a marker allele into a chromosome
of one species.
b. Make this segment homozygous by appropriate crosses.
c. Cross with a second species. The hybrid carries one copy of
the chromosome with the
insert.
d. Backcross repeatedly to second species, selecting individuals with
the marker each
generation.
e. Each generation, recombination shortens the segment from the first
species' chromosome
f. After, say, 15 generations, the segment from the first species is
very small.
3. Procedure: Testing effects of introgressed segment on fertility.
a. Cross a male and female, each heterozygous for the introgressed
segment, to
produce individuals that are homozygous for that segment.
4. Repeat this procedure for many introgressed segments located in different parts of the genome.
a. Each segment that has an effect on viability or fertility indicates
the presence of at
least one incompatability gene within that segment.
b. Hence, can obtain a mininimum estimate of the number of incompatibility
genes of
various types.
B. Example: True et.al. 1996. Genetics 142: 819-837.
1. Backcrossing
a. Introduced a marker using P-element (a transposon) tagging into
D. mauritiana.
b. P-element carried mini-white gene affecting eye color, which allows individuals
carrying the marker to be scored easily.
c. P-elements insert essentially randomly all over the genome.
d. Obtained single inserts in 185 individuals, all in different autosomal
locations.
e. Each of these individuals was used to establish a backcross line
and the corresponding
marker and flanking DNA was introgressed into D. simulans.
f. Each line was then tested for the effect of the introgressed segment
on viability and
fertility.
2. Results
a. Results presented in table, which shows the number of introgression
lines in each
category:
Male Male Male
fertile sterile untested
Female fertile
112 53
---
Female sterile
6 4
2
Female untested ---
8 ----
b. Of the 175 segments, 112 had no detectable effects on viability
or sterility in either sex.
c. Of the remaining segments, 53 reduced only male fertility, while
6 reduced only female
fertility and 4 reduced both male and female fertility.
d. In other words, about 9 times as many segments had incompatibility
alleles affecting
male fertility.
3. Conclusion:
Incompatibility alleles affecting male fertility accumulate much faster
than those
affecting female fertility, supporting the differential accumulation theory.
C. Differential Accumulation on X chromosome.
1. Wu et
al. performed a similar experiment introgressing X-chromosome segments
from D.mauritiana into D. simulans.
2. Results indicate that there are more than 40 incompatibility genes
on the X-chromosome
contributing to male sterility.
3. By contrast,
there are apparently no X-chromosome incompatibility genes affecting female
fertility (this is demonstrated by complete fertility of attached-X females).
4. Conclusion:
Results support the differential accumulation theory.
V. Conclusions
A. As a general phenomenon, Haldane's rule seems to be caused by several different phenomena.
1. In some cases, it seems to be due to the type of recessivity of incompatibility
interactions
envisioned by Muller's theory.
2. In other cases, it seems to be due to a generally more rapid accumulation
of alleles affecting
male hybrid inviability/sterility than alleles affecting female hybrid inviability/sterility.
3. There is some evidence that there may also be more rapid accumulation
of incompatibility
alleles on the X chromosome than on autosomes, which can account for not
only Haldane's
rule but also the Large-X effect.
B. This multiplicity of explanations seems to be the rule in evolutionary
biology: the same phenomenon
may have different explanations in different groups of organisms.