July 20, 2007

Broad Complex-tramtrack-bric-a-brac

Acording to Nicholas Wade, "Scientists Find Genetic Link for a Disorder (Next, Respect?)", NYT, 7/19/2007

Many human genes were first described by geneticists who identified counterpart genes in the laboratory fruitfly. Fruitfly researchers consider it a matter of pride to give genes colorful names, but these are often moderated or disguised by medical researchers who feel absurd names will not help attract research funds. BTBD9, the gene in today's two studies, stands for broad complex-tramtrack-bric-a-brac-domain 9.

You can sometimes learn the story behind fruitfly gene names by consulting FlyNome:

Here at FlyNome, you can find the answer to that burning question: How exactly did they come up with the name for that gene? If you'd like to know the story behind a Drosophila gene name, this is the place for you. Simply type in the gene name above, or go to the search page.

For example, FlyNome knows that bruchpilot (BRP), named in Wagh et al. (2006) Neuron: 49:833-844,

is German and means crash pilot. The gene is named after a famous German movie from the nineteenthirties "Quax, der Bruchpilot" about a pilot who always crashes his planes but survives. This name was chosen because the first flies with a severe reduction of the encoded protein due to RNAi knock-down could not sustain stable flight but crashed to the ground when released into open air.

It also knows that ken and barbie (KEN) was so named, by Kuhnlein, R.P. et. al (1998) Mech. Dev. 79(1,2):161--164, because

The external genitalia are absent in some males and females. Thus these flies are named after the famous dolls who also lack these "features."

(Why the scare quotes around features, I wonder...)

And we can learn from FlyNome the story behind fear of intimacy:

In foi mutants, gonad coalescence is affected. In wild type, the germ cells and gonadal mesoderm cells normally coalesce tightly together during stage 14 of embryogenesis. Since these cells fail to undergo the "big group hug" of coalescence in the mutant, it was named fear of intimacy.

But unfortunately, FlyNome doesn't have anything to say about broad complex-tramtrack-bric-a-brac-domain 9, or BTBD9, or even tramtrack or bric-a-brac.

The FlyNome FAQ continues:

If the story for a gene in which you're interested isn't in our database, you can ask someone to add it. Go to the request page where you can send an email request to an author of a paper referencing the gene. Once that person has entered the information in the FlyNome database, you'll be able to find the answer to why the gene is named as it is!

So I went to FlyBase -- but a search for BTBD9 also comes up empty there. FlyBase does know about bric a brac 1 (bab1) -- also bab2 -- and about tramtrack (ttk), and perhaps these are related. FlyNome has no story to tell about these genes, but the FlyBase description of bab1 gives a clue about its probable origin:

It is involved in the biological processes described with 16 unique terms, many of which group under: regulation of development; sex differentiation; primary metabolism; regulation of developmental pigmentation; organ morphogenesis; metamorphosis (sensu Insecta); regulation of metabolism; behavior; organismal physiological process; sex determination; establishment and/or maintenance of chromatin architecture. 24 alleles are reported. The phenotypes of these alleles are annotated with 25 unique terms, many of which group under: adult segment; metatarsus; metathoracic metatarsus; female reproductive system; adult mesothoracic segment; adult prothoracic segment; peripheral nervous system; ovariole; gonad; nervous system.

Next, I tried a search at euGenes. Here a search turns up BTBD9 as a human gene, in a cross-reference to fruitfly gene CG1826. The full name is given as "BTB (POZ) domain containing 9", with other cross-references to mosquito, mouse, worm and rat genes.

A wildcarded euGenes search for BTB turns up 326 hits. The string BTB itself, turns up the D. melanogaster gene bumper-to-bumper, FlyBase GBgn0015368. But as we'll soon see, this seems to be a false lead. (Anyhow, FlyNome doesn't yet know the story behind "bumper-to-bumper" either).

A further euGenes search indicates that BTBD9 is one of a series of (non-fruit-fly) genes: BTBD1 = "BTB (POZ) domain containing 1", BTBD2 = "BTB (POZ) domain containing 2", BTBD3 = "BTB (POZ) domain containing 3", etc.

The "BTB/POZ domain" is a term that defines a pretty common and important class of genes/proteins, apparently first discussed in O. Albagli et al., "The BTB/POZ domain: a new protein-protein interaction motif common to DNA- and actin-binding protein", Cell Growth Differ 6 (9), 1193-8, 1995, which says:

The BTB (3) (for Broad Complex, tramtrack and bric à brac) or POZ (4) (for poxviruses and zinc finger) is an approximately 120-amino acid conserved and hydrophobic domain present generally at the NH2-terminal end of numerous proteins including Zinc finger, poxvirus, and actin-binding proteins.

Reference (3) is S. Zollman et al., "The BTB domain, found primarily in Zinc finger proteins, defines an evolutionanily conserved family that includes several developmentally regulated genes in Drosophila", PNAS 91: 10717-10721, 1994. And this confirms the terminological history, though not the story behind it:

The Drosophila bric à brac protein and the transcriptional regulators encoded by tramtrack and Broad-Complex contain a highly conserved domain of ~115 amino acids, which we have cafled the BTB domain. We have identifed six additonal Drosophila genes that encode this domain. Five of these genes are developmentally regulated, and one of them appears to be functionally related to bric a brac. The BTB domain defines a gene family with an estimated 40 members in Drosophila. This domain is found primarily at the N terminus of zinc finger proteins and is evolutionarily conserved from Drosophila to mammals.

So the (syntactic) structure of BTBD9 is [[[Broad Complex][Tramtrack][Bric-a-brac]] Domain] (containing) 9] -- that is, the ninth in a series of genes containing a region coding for the BC/T/Bab amino-acid sequence. Apparently this sequence (or genes coding for it among other things) was independently identified three times, under different names ("Broad Complex", "Tramtrack", "Bric a brac").

The BTB/POZ domain also comes up in the famous fruitless gene, for which FlyNome does have a story to tell:

Fruitless is responsible for all aspects of courtship in Drosophila. The first fru mutants courted males and females indiscriminately. The gene was to be called "fruity", but the more P.C. "fruitless" was chosen.

Posted by Mark Liberman at July 20, 2007 08:11 AM