The humble chicken has provided humanity with meat, eggs, and wake-up calls for centuries, and new research probing the bird's DNA may point to an expansion of another role for the flightless fowl: biomedical model organism.

Image: Michael Gäbler via Wikipedia Commons

Uppsala University functional genomicist Leif Andersson and colleagues used cutting-edge sequencing technology to comb the chicken genome and identified some genetic signatures of domestication, according to a study published today (10th March) on Nature's website. These genetic signatures code for traits that make domestic chickens useful as egg or meat producers, but in humans, changes to homologous genes can lead to complex "lifestyle diseases" -- such as obesity and diabetes. This suggests that biomedical researchers may be able to use the domesticated chicken to research these conditions.

Scientists already use the chicken to study some human diseases, and this study suggests the animal could become even more important in the lab, said University of Arkansas physiologist Wayne Kuenzel, who wasn't involved with the study.

"It's a really useful paper to highlight what the chicken can do," he told The Scientist. Kuenzel himself has studied the relationship between diet and intracranial cerebrospinal fluid pressure in chickens as a model of human headaches.

Through decades of selective breeding, humans have developed several different chicken strains that display distinct traits -- such as rapid growth in chickens used for meat or increased reproductive output in egg-laying chickens -- the underlying genetics of which can now be interrogated using modern sequencing. "It's a bit like an experiment that's been going on for 100 years," said University of Edinburgh comparative genomicist David Burt, who did not participate in the research.

Andersson and his coauthors performed high-throughput sequencing on eight populations of domestic chickens -- originally sequenced in 2004 using the more laborious and expensive Sanger method -- as well as one of the chicken's closest wild relatives, the red jungle fowl. They found more than 7 million single nucleotide polymorphisms and more than 1,000 deletions. They also found evidence of several "selective sweeps," when changes in the genome become fixed over time as breeders select for desirable phenotypic traits.

The researchers uncovered one such selective sweep -- a mutation in the gene that codes for the thyroid stimulating hormone receptor (TSHR) -- shared by all domestic chicken breeds. Finding such an allele shared by all chicken breeds is no small matter, explained Andersson, because chickens are on average about five times more genetically diverse than humans.

Susan Lamont, a geneticist at Iowa State University who was not involved with the study, said that chickens may yield important insights into diseases, such as obesity and diabetes, that are common in increasingly sedentary human populations. TSHR, for example, plays a crucial role in metabolic pathways and in regulating photoperiod control of reproduction in all vertebrates. "What we're seeing is the opportunity to look at the genes that are likely going to be good models for the same kinds of issues in humans," she told The Scientist.

There are other reasons why chickens, which have already been used to study epilepsy, autoimmune diseases, and the human pigment disorder vitiligo, make good biomedical models, Kuenzel said. For one thing, he noted, like humans, chickens are bipedal, diurnal organisms (unlike mice and rats). Also, embryonic development in chickens takes place largely outside the mother's body in eggs, making studying that process easier than in placental mammals. "The beauty of the chicken is that you can follow the development and do very detailed expression studies during development," said Andersson.

In total, Andersson and his colleagues found more than 30 genetic loci that appeared to be signatures of domestication in different domestic chicken breeds. TSHR and two other selective sweeps were (to some degree) shared by all domestic chickens, and the others seemed to correspond to physiological traits associated with a particular breed's role in the human food chain. "Every one of those [loci] is like a follow-up project, where you need to do more research," Andersson said.

His group is currently exploring TBC1D1 -- a gene involved in the regulation of insulin-mediated glucose uptake in muscles that was similarly mutated in all chicken breeds used for meat production. TBC1D1 has been associated with susceptibility to obesity in humans, Andersson said. "Now we can really study that gene in detail."


Related stories:

Immunity for breakfast?
[March 2008]

Chicken in the city
[11th May 2007]

Why did the chicken cross the DNA?
[6th December 2000]