COLLEGE STATION, TX-In a new study published in PLoS Genetics, an international team of researchers report that two independent mutations are required to explain the development of the sex-linked barring pattern in chickens. Both mutations affect the function of CDKN2A, a tumor suppressor gene associated with melanoma in humans.
Leif Andersson, Uppsala University, Swedish University of Agricultural Sciences and Texas A&M University, led the study that illustrates how useful domestic animals are as models for evolutionary processes in nature. Andersson argues that a similar evolution of gene variants comprising multiple genetic changes affecting the function of a single gene is the rule rather than the exception in natural populations.
Research in pigmentation biology has made major advances the last 20 years in identifying genes controlling variation in pigmentation in mammals and birds; however, the most challenging question is still how color patterns are genetically controlled. Birds are outstanding as regards the diversity and complexity in color patterning, according to Andersson.
The study published April 7 has revealed the genetic basis for the striped feather characteristic of sex-linked barring. Sex-linked barring refers to the alternating of pigmented (usually red or black) and apigmented (white) stripes that occur on certain breeds of chickens.
One example is the French breed Coucou de Rennes, the name of which refers to the fact that its plumage color resembles the barring patterns present in the common cuckoo (Cuculus
canorus). The sex-linked barring locus is on the Z chromosome. In chickens, as well as in other birds, the male has chromosomes ZZ while females have ZW.
“Our data show that sex-linked barring is caused by two independent mutations that act together. One is a regulatory mutation that increases the expression of CDKN2A. The other changes the protein sequence and makes the protein less functionally active,” Andersson said. “We are sure that both mutations contribute to the sex-linked barring pattern because we have also studied chicken that only carry the regulatory mutation and they show a very pale plumage with only weak dark stripes. Thus, this represents an evolutionary process in which the regulatory mutation occurred first followed by the mutation affecting the protein structure. The combined effect of the two mutations causes an even more appealing phenotype for the human eye.
Anderson also believes the most important reason for the extensive color variation among the domestic animals is that we appreciate its diversity, as long as the mutations underlying the variation are not causing health issues for the animals.
CDKN2A is a well-studied tumor suppressor gene that takes part in the regulation of cell division and cell survival. Mutations that inactivate CDKN2A are the most common explanation for familiar forms of melanomas in humans. However, the great majority of melanoma cases are not associated with a strong genetic risk factor.
“The gene variant underlying sex-linked barring has an opposite effect compared with the mutations causing melanoma in humans. Sex-linked barring is associated with a gene variant that makes CDKN2A more active, leading to a cyclic deficit of pigment cells and causing the white stripes during the development of an individual feather. It appears that pigment cells are particularly susceptible to changes in the function of CDKN2A as inactivating mutations in humans are associated with melanoma but rarely other cancer forms and activating mutations cause sex-linked barring in chickens but no other side effects are known,” said Doreen Schwochow Thalmann, PhD student and first author of the paper.
“It is fascinating that a large proportion of chickens used for egg and meat production around the world carry these mutations in a tumor suppressor gene. An example of such a breed is White Leghorn, which is one of the most prominent breeds used for egg production, but sex-linked barring is not apparent in these breeds because they also carry the dominant white color that eliminates all pigment production and masks the effect of sex-linked barring,” Andersson said.