A personal account of the naming of the klingon gene.

Samanth Butler

For my thesis project, I chose to work on an enhancer trap line with the unromantic but practical designation, H214. "H"because lacZ is expressed from the hsp70 promoter and "214"presumably because it was the 214th line that my thesis advisor, Yash Hiromi, isolated in a screen for such lines. I considered H214 to be a good prospect for a thesis project because of its unique expression pattern. The H214 line was the only marker known that specifically labels a single neuronal cell type in the developing eye, the R7 photoreceptor neuron, and it did so independently of the information that specifies the final position of the R7 cell. Thus, it could be reasonably inferred, the associated gene would have a role in determining the identity of R7.
Somewhere during the six years that I worked on the H214 line, Sandip Ray and I cloned the associated gene (which we temporarily called h214) and characterised its expression pattern (which mirrored that of the H214 line). h214 turned out to be an adhesion molecule of the Ig domain superfamily that could mediate the homophilic adhesion of S2 tissue culture cells. But what did it actually do in the developing eye? To answer this I attempted to characterise h214 mutants, made from imprecisely excising the P-element insertion. And here the trouble began. Apart from the fact that the h214 gene was essential (mutant animals do not survive the second instar larval stage) I could find no defect in eye development in the mutants. All the photoreceptor neurons formed normally with their axon projections intact.
This result led to two problems: a potentially rather uninteresting paper and difficulty permanently naming the gene. The cleverest Drosophila gene names refer to their mutant (usually loss-of-function) phenotype. My personal favourite is the tinman gene, which affects heart development (Americans may have an easier time understanding this one), and I also love the Heidelberg names, such as hedgehog, armadillo, windbeutel, torpedo etc. However, it is tricky to be clever when you lack phenotypic clues. Thus, it looked as if we would have to turn to an alternative strategy, often employed for both vertebrates and invertebrates, naming the genes based on an educated guess as to the function of the protein. Examples here are fasciculin, integrin and neuregulin. In this latter strategy the two requirements appear to be wishful thinking and that the gene name end in "in". I had, however, seen a further naming strategy in action, next door in the Schedl lab. Martin Muller had named his genes involved in pairing sensitivity after liquors. grappa was the most interesting at the time. This approach was considered a rare example of the gene name saying more about the author than the gene.
Permanently naming the gene h214 was not an option. The name "h214"lacked imagination and would have showed a sign of defeat of sorts. In addition, we risked the gene being re-named by the next person isolating it by an alternative method. I wondered if I could adopt both of the last two naming approaches I described above. Could "my"gene name be both relevant to the unknown function of h214 and relevant to me? Perhaps. h214 was a presumptive adhesion molecule. I was a Star Trek fan. Klingon was the answer. We mulled over this possibility in lab and tried to get cleverer. How about the Klingon word for eye? Yash, however, strongly indicated that he would not be able to give a seminar using this name, after hearing my guttural estimation of what such a word would sound like. Thus, I chose klingon.
We still do not know precisely what klingon does. My later misexpression studies have suggested that klingon may have a redundant role correctly positioning the neural precursor cells so that they make the right contacts within the developing unit eye. However, I adhere to the possibility that the klingon gene has other roles yet to be uncovered. After all, surely the namers of Notch could not have anticipated that their wing defect gene would be so pleiotropic?