The Bunny Colour Code
(April 17th, 2014) On Easter, children all over Europe shall begin to keenly search their neighbourhood for gifts, chocolate eggs, and the ever-elusive Easter Rabbit. Timed to perfection, scientists have identified the genetic basis for colour variations in rabbits.
The coat colour phenotype in rabbits is described as ‘dense’ and ‘dilute’. As the word suggests, ‘dilute’ rabbits are lighter in coat colour, i.e. they possess comparably less pigment in each hair when compared to ‘dense’ (wild type) rabbits. In these bunnies, the black pigment eumelanin is diluted to a blue or grey colour and the chocolate-y pigment phelomelanin is diluted to a lilac or fawn colour.
Rabbit breeders had long known that the inheritance of the dense phenotype was dominant and that of the dilute phenotype recessive. However, the mutation that leads to this difference was unknown until very recently. Researchers from the University of Bologna, Italy, and the French National Institute for Agricultural Research (INRA) have discovered that the dilution phenotype in rabbits is caused by a mutation in the Melanophilin (MLPH) gene.
The team zeroed in on the MLPH gene based on the knowledge that similar coat colour in mice arose due to mutations in the myosin VA, Rab27a and MLPH genes. All of these genes play a vital role in visible pigmentation. The three proteins they code for are part of a protein complex that helps to secure melanosomes (pigment–producing cell organelles) to the cytoskeleton of pigment-producing cells. The genes are hence indispensable to proper pigment distribution in hair and skin.
In human beings, a mutation in the MLPH gene results in a rare autosomal disorder known as the Griscelli syndrome type 3. Affected individuals are observed to have silver-grey hair, eyebrows and eyelashes. Furthermore, irregular pigment distribution along the hair shaft leads to microscopic clumping. The disorder is recessively inherited and is not known to have any immunological or neurological manifestations.
The MLPH gene regulates the early stages of pigment production; therefore any mutation in its sequence will have an effect on both black and chocolate bunnies. The resulting dilute bunnies have a lighter appearance as pigment clumping along the length of the hair influences the reflection of light.
In this study the scientists began by generating three half sibling families of ‘Checkered Giant’ rabbits. A dilute male, homozygous for the recessive mutation, was crossed with three unrelated black female rabbits. Two of these females were born from black (dense) and grey (dilute) parents, and were hence thought to be heterozygous for the dilute mutation. The third one was thought to be homozygous for the wildtype allele based on pedigree information.
The first generation (F1) of baby bunnies coming from heterozygous mothers, were both black and grey, while those from the homozygous mother were all black. This outcome confirmed, as expected, that the dilution mutation was indeed recessively inherited in rabbits.
Analysing the DNA of the rabbits, a mutation in the MLPH gene was observed that was ‘completely associated with coat colour phenotype’. However, this mutation did not bring about the dilute colouration in all rabbits studied. This meant that a different mutation had to be responsible for the dilution, and that the current mutation was in fact linked to this one.
To resolve this mystery, a large part of the MLPH gene was sequenced from 18 rabbits of assorted breeds and colour. A frame-shift deletion (g.549853delG) was ultimately found to lead to the dilute coat colour, i.e. the deletion of nucleotides in a DNA sequence causes a shift in its reading frame. These observations were further confirmed in 198 rabbits belonging to 23 different breeds. All bunnies homozygous for the mutation possessed dilute coat colour, while those heterozygous for it were dense. This pattern reinforced the belief that this mutation is recessively inherited.
So if you do happen to see the Easter bunny in the days to follow, make sure to take a close look at his coat colour. If he happens to be dilute, perhaps you could exchange your new found knowledge for some chocolate eggs! Happy Easter!