Sonic the Hedgehog in the Genetic Multiverse

One gene is named after Sonic the Hedgehog, the blue hedgehog hero from video games and comics. How and why?

While working as a postdoc in Tabin’s lab at Harvard, Robert Riddle glanced at a journal his wife had brought. The magazine ad featured Sonic the Hedgehog, a fast blue Japanese hedgehog from video-game. And Riddle decided to name a protein and the gene that encodes it after that video game character.

Robert Riddle’s great interest is the embryonic development of the brain. And this gene and protein have very important roles in that. So important that if something goes wrong, the development of the brain will go in the wrong direction, so a phenomenon called holoprosencephaly can occur, when the two hemispheres of the brain are not created. And not only that – this gene and its product are very important for controlling the formation and development of organs during embryonic development. Also, if something goes wrong with this gene in an adult, if there is an abnormal activation of the gene, cancer occurs in various organs, including the brain and pancreas.

Riddle based his work on the work of the American-German duo Christiane Nüsslein-Volhard and Eric Wieschaus, who were already working on the study of genetic control of embryonic development in the early 1980s, using a typical model organism – the fruit fly (Drosophila melanogaster). The two discovered that there are genes whose activation is crucial for proper embryonic development, and if there is a “wiggle”, abnormal development will occur. These genes, which controlled the formation and development of organs and segmentation of the fruit fly, were named according to the shape of the mutant larvae of the fly – for example, a cucumber or a hedgehog. Christiane and Eric received the Nobel Prize in Medicine or Physiology in 1995 for this research.

In the case of fruit fly larvae with a disturbed function of one specific gene, they would appear as teeth, small spines. Since the larvae were associated with a hedgehog, this gene was named “hedgehog”, and its abbreviation is hh.

Later, the counterparts of this gene were discovered in vertebrates, moreover, not one but even three genes, so it is a whole family of “hedgehog genes”, three gene homologues.

Hedgehog equivalents (homologs) in vertebrates were discovered by Philip Ingham, Andrew P. McMahon and Clifford Tabin. The aforementioned Robert Riddle worked in Clifford Tabin’s lab at Harvard.

The first gene was named after the desert hedgehog (Paraechinus aethipicus), the desert hedgehog homolog gene and protein (Dhh code for protein, DHH for genes), the second after the Indian hedgehog (Paraechinus micropus), the Indian hedgehog homolog protein and gene (Ihh code for protein and IHH designation for the gene).

The third hedgehog gene is the sonic hedgehog homology gene (SHH), and its protein sonic hedgehog homolog protein (Shh).

Although SHH and Shh are mostly related to brain development, this gene and protein also play important roles in tooth development and lung development.

Today, in fact, the full name of this gene is less often used and the standard abbreviations SHH and Shh are used more for the gene and protein respectively (notice how the abbreviation for the gene is usually in italics), because it would be somewhat unusual to tell patients and their families sonic hedgehog homologue. This is not the only case of unusual names in gene nomenclature.