The Heterotrimeric G Protein Genes of Caenorhabditis elegans
27
pendent pathways for the three repellents tested. The most likely candidate cells involved in aversion are ADL and ASH (Bargmann and Mori
1997). Finally, the effect of overexpression of GPA-5 on olfaction led us
to test functional redundancy between gpa-5 and odr-3. Surprisingly, a
double mutant of gpa-5 and odr-3 showed wild-type chemotaxis to
2,4,5-trimethylthiazole (tmt), but reduced chemotaxis to other odorants
(Table 2; Fig. 5D), suggesting that gpa-5 is a negative regulator of tmt
perception.
Mutations in only two Ga subunits, gpa-3 and odr-3, have profound
effects on perception. The other genes probably have more subtle functions, which could be masked by functional redundancy, as was described for odr-3 and gpa-2 (Roayaie et al. 1998). Given the expression
patterns of multiple a subunit genes per neuron this seems certainly
possible. Alternatively, these genes could be involved in behaviors that
have not yet been tested, for example perception of other compounds, or
they may have negative regulatory functions (like gpa-5). It will be
interesting to see if a similar ratio of central to regulatory genes holds
true also in other systems. Perhaps forward genetics has biased our focus
in functional analysis to genes with clear phenotypes, and has caused an
underestimation of the importance of regulatory pathways.
2.2.5 Why Would C. elegans Need 14 or More Ga Subunits
for Perception?
The answer to this question probably resides in the simplicity of the
animal. Mammals are thought to have each of their millions of olfactory
neurons devoted to one specificity (Buck 1996). The adult C. elegans
hermaphrodite has only 16 pairs of neurons that are in direct contact
with the animal's environment. However, the animal senses much more
than 16 compounds, and responds specifically to different stimuli perceived via the same cell (Bargmann et al. 1993; Kaplan and Horvitz
1993; Colbert and Bargmann 1995). To do so, C. elegans needs multiple
signal transduction pathways per cell. Analyses of the expression patterns of some of the approximately 650 putative serpentine receptor
genes (Troemel et al. 1995) and 29 guanylyl cyclases (Yu et al. 1997)
indicate that indeed, each chemosensory cell expresses several receptor
genes. Our data suggest that the nematode also uses multiple Ga subunit
27
pendent pathways for the three repellents tested. The most likely candidate cells involved in aversion are ADL and ASH (Bargmann and Mori
1997). Finally, the effect of overexpression of GPA-5 on olfaction led us
to test functional redundancy between gpa-5 and odr-3. Surprisingly, a
double mutant of gpa-5 and odr-3 showed wild-type chemotaxis to
2,4,5-trimethylthiazole (tmt), but reduced chemotaxis to other odorants
(Table 2; Fig. 5D), suggesting that gpa-5 is a negative regulator of tmt
perception.
Mutations in only two Ga subunits, gpa-3 and odr-3, have profound
effects on perception. The other genes probably have more subtle functions, which could be masked by functional redundancy, as was described for odr-3 and gpa-2 (Roayaie et al. 1998). Given the expression
patterns of multiple a subunit genes per neuron this seems certainly
possible. Alternatively, these genes could be involved in behaviors that
have not yet been tested, for example perception of other compounds, or
they may have negative regulatory functions (like gpa-5). It will be
interesting to see if a similar ratio of central to regulatory genes holds
true also in other systems. Perhaps forward genetics has biased our focus
in functional analysis to genes with clear phenotypes, and has caused an
underestimation of the importance of regulatory pathways.
2.2.5 Why Would C. elegans Need 14 or More Ga Subunits
for Perception?
The answer to this question probably resides in the simplicity of the
animal. Mammals are thought to have each of their millions of olfactory
neurons devoted to one specificity (Buck 1996). The adult C. elegans
hermaphrodite has only 16 pairs of neurons that are in direct contact
with the animal's environment. However, the animal senses much more
than 16 compounds, and responds specifically to different stimuli perceived via the same cell (Bargmann et al. 1993; Kaplan and Horvitz
1993; Colbert and Bargmann 1995). To do so, C. elegans needs multiple
signal transduction pathways per cell. Analyses of the expression patterns of some of the approximately 650 putative serpentine receptor
genes (Troemel et al. 1995) and 29 guanylyl cyclases (Yu et al. 1997)
indicate that indeed, each chemosensory cell expresses several receptor
genes. Our data suggest that the nematode also uses multiple Ga subunit