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From Sonic hedgehog to sasquatch

Expression of sonic hedgehog gene
Sonic hedgehog is a fundamentally important gene in human development. So why does it have such an odd name?

Its roots lie in the traditions of genetics research. Modern genetics owes much to Thomas Hunt Morgan who was the first to use fruit flies in research, in the search for the gene in the 1920s. He was looking for a mutation that changed the fly's eye colour - a nice obvious phenotypic effect. The mutation was known as 'white' and other mutations that affected eye colour were given similarly appropriate names.

Thus began the tradition of naming fly genes after their mutant phenotypes. It has also given fly geneticists a chance to exhibit their inner creativity, learning and, on occasion, sly sense of humour.

A series of mutant strains with sterility were named after European Royal houses, which suffered similar problems; a set of strains with long-term memory issues were named after Pavlov's dogs. Inspired by the Wizard of Oz, flies lacking a heart became known as 'tinman'.

And who says scientists are not up with popular culture? The 'grunge' mutation was so called because it affected activity of the 'teeshirt' gene, while flies which died prematurely were named 'kenny', in honour of the 'South Park' character.

Some names are more risqué. Flies with a disrupted 'ken and barbie' gene lack external genitalia. 'Lush' flies have a fondness for alcohol, while 'cheap date' flies are especially susceptible to its effects. Flies with the misfortune to inherit a 'stuck' mutation have difficulty disengaging after mating, while 'baboon' flies have large anal pads

Although physical appearance commonly inspires gene names, so too does behaviour. Flies with deformed wings that could run but not take off were named 'taxi' (others include 'grounded', 'rhea' and 'moa'). 'Ether a go go' flies jiggle uncontrollably in the presence of ether.

So what of 'Sonic hedgehog'? This name originated via the famous developmental screen carried out by Ed Lewis, Christiane Nüsslein-Volhard and Eric Wieschaus, which earned them the 1995 Nobel Prize for Physiology or Medicine. The screen identified large numbers of mutants affecting embryogenesis, one of which was named 'hedgehog' - mutant embryos were short, stubby and their backs were coated in a mass of tiny spines. When similar genes were found, they were given related names - including 'Indian hedgehog', 'Desert hedgehog' and 'Sonic hedgehog'. (Rather delightfully, a gene found in zebrafish was called 'tiggywinkle hedgehog'.)

Only later, usually, does it become clear what the full role of a gene is. 'Shh' has turned out to have many important roles, human digit formation being one of them.

Researchers working with other organisms tend to be more restrained in their naming conventions, though some mice strains have imaginative names - one, known as 'sasquatch', had duplicated digits, and turned out to be due to altered regulation of the 'Shh' gene. Nowadays, most genes get a series of letters and numbers related to their possible function or similarity to known genes.

Sometimes, these dull but functional annotations include a reminder of their origins. Much research centres on so-called SMAD proteins, or to give them their full names, 'small mothers against death' proteins.

Though engaging, the fly approach has caused problems. A proposal to call one strain 'velcro' was vetoed by the product's manufacturers, while some Japanese businessmen were none too pleased when a fruit fly gene was linked to human tumours - thanks to “Pokemon causes cancer” headlines. More seriously, the fact that genes are found across species, and may be linked to medical conditions, can raise sensitive issues. Would you like to be told that your child's condition was linked to a gene called 'Sonic hedgehog', 'sasquatch' or 'baboon'?

Image: Lateral view of a stage 15 chick embryo showing the regions where the sonic hedgehog gene is switched on (purple). Abigail Tucker, Wellcome Images.

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