What's in a name?

Abstract

We humans love to name things, be they living or inanimate. Names help us as a mental short cut, so that when we refer to an object or a living being we do not have to resort to lengthy descriptions of their attributes. Names simplify and smoothen our conversations. Many names directly reflect specific characteristics of the named, such as “eumelanin” (from Greek ευ = good, true, and μελασ = black, dark), but others are entirely devoid of any inner meaning. A typical example for this latter group is “q” for the long arm of a human chromosome. That does not mean, however, that the choice of “q” does not have its history. As the story is told, battles raged at a Chicago conference in 1966 about how to name the chromosome arms. Some argued for “s” and “l” (for short and long). The German-born American geneticist Klaus Patau, of fame for having discovered the cytogenetic basis of trisomy 13, argued that the short arm should be called “k” (for kurz, German for short), but the French geneticist Jérôme Jean Louis Marie Lejeune, of fame for having co-discovered the cytogenetic basis of Down syndrome, strongly argued for “p” (for petit, French for short). Nevertheless, the common “l” (for English long; French long; or German lang) could be confused with “1,” and so Lionel Penrose, a British psychiatrist and medical geneticist who is known, among many other things, for having associated the risk for Down syndrome with maternal age, proposed a compromise: “p” and “q,” simply because “q” followed “p” in the alphabet and perhaps because p + q = 1 (one chromosome), in allusion to the Hardy-Weinberg equilibrium, where the frequency of the dominant allele p + the frequency of the recessive allele q also equals 1. Why do I write about these hard-fought battles of a distant past? Well, HUGO, the Human Genome Organization, recently redefined MITF, a gene dear to our hearts. They now call it “melanogenesis-associated transcription factor” instead of the well-known “microphthalmia-associated transcription factor.” We all agree, of course, that MITF mutations cause microphthalmia (=small eyes) only in mice and not usually in humans or many of the other species in which its homologues are found. But neither do MITF mutations just cause deficiencies in melanogenesis. No, MITF is a jack-of-all-trades, involved in many physiological processes in melanocytes and melanoma, which include the regulation of cell proliferation, autophagy, and even DNA repair. It also operates in many other cell types, such as in osteoclasts and mast cells, and in a variety of organs, such as kidneys and, in Drosophila, the gut. It is called microphthalmia-associated transcription factor for purely historical reasons. The corresponding locus was discovered in mice by Paula Hertwig in 1942 (for a short description, see PCMR 23, 729–735, 2010). She originally named it “m” for microphthalmia, perhaps because the small-eye phenotype seemed the most unusual to her or because the original cross also segregated an allele for albino, which independently made some offspring white (though not microphthalmic). Hans Grüneberg, the eminent mouse geneticist, then proposed the symbol “mi” because “m” was already taken for another locus, misty. The cloning of the mi gene was reported in 1993 and in negotiations with the International Committee on Standardized Genetic Nomenclature for Mice and HUGO, we later named it Mitf rather than “Mi” because gene names required at least four letters and because it indeed encoded a transcription factor. Redefining it now as “melanogenesis-associated transcription factor” obfuscates this historical context and replaces an admittedly restricted definition with one that is equally restricted. This is totally unnecessary, only creates confusion for people working with different species, and does a disservice to the gene's interesting history of discovery and analysis. Hence, I urge everyone working in this area to ignore HUGO's unenlightened redefinition and continue using the established term. After all, as Eirikur Steingrimsson has pointed out, if one really wanted to be consequential, using the term “melanogenesis-associated transcription factor” would also require a renaming of the gene from MITF to METF, a change even HUGO did not have the courage to propose!