The Questions of Developmental Biology

It is difficult for a mutation to actually affect development (Nijhout and Paulsen 1997).
It is the rare mutation that is 100% penetrant. Stress, however, in the form of environmental
factors such as temperature, can overpower the buffering systems of development and alter the
phenotype. Moreover, the altered phenotype then becomes subject to natural selection, and if
selected, will evebtually appear without the stress that originally induced it. Waddington called
this phenomenon genetic assimilationChapter21). For instance, when Waddington subjected
Drosophila larvae of a certain strain to high temperatures, they lost their wing crossveins.
After a few generations of repeated heat shock, the crossveinless phenotype continued to be
expressed in this population even without the heat shock treatment. While Waddington's results
look like a case of "inheritance of acquired characteristics," there is no evidence for that view.
Certainly, the crossveinless phenotype was not an adaptive response to heat. Nor did the heat
shock cause the mutations. Rather, the heat shock overcame the buffering systems, allowing
preexisting mutations to result in mutant phenotypes rather than wild-type phenotypes.
In 1998, Suzanne Rutherford and Susan Lindquist showed that a major agent responsible
for this buffering was the "heat shock protein" Hsp90. Hsp90 is a protein that binds to a set of
signal transduction molecules that are inherently unstable. When it binds to them, it stabilizes
their tertiary structure so that they can respond to upstream signaling molecules. Heat shock,
however, causes other proteins in the cell to become unstable, and Hsp90 is diverted from its
normal function (of stabilizing the signal transduction proteins) to the more general function of
stabilizing any of the cell's now partially denatured peptides (Jakob et al. 1995; Nathan et al.
1997). Since Hsp90 was known to be involved with inherently unstable proteins and could be
diverted by stress, it was possible that Hsp90 might be involved in buffering developmental
pathways against environmental contingencies.
Evidence for the role of Hsp90 as a developmental buffer first came from mutations of
Hsp83, the gene for Hsp90. Homozygous mutations of Hsp83 are lethal in Drosophila.
Heterozygous mutations increase the proportion of developmental abnormalities in the population
into which they are introduced. In populations of Drosophila heterozygous for Hsp83, deformed
eyes, bristle duplications, and abnormalities of legs and wings appeared (Figure 22.28). When
different mutant alleles of Hsp83 were brought together in the same flies, both the incidence and
severity of the abnormalities increased. Abnormalities were also seen when a specific inhibitor of
Hsp90 (geldanamycin) was added to the food of wild-type flies, and the types of defects differed
between different stocks of flies. The abnormalities observed did not show simple Mendelian
inheritance, but were the outcome of the interactions of several gene products. Selective breeding
of the flies with the abnormalities led over a few generations to populations in which 80 90% of
the progeny had the mutant phenotype. Moreover, these mutants did not keep the Hsp83
mutation. In other words, once the mutation in Hsp83 had allowed the cryptic mutations to
become expressed, selective matings could retain the abnormal phenotype even in the absence of
abnormal
Hsp90.