First analysis of chicken genome offers many new insights

Red jungle fowl
Red jungle fowl

The first detailed analysis of the chicken genome has identified a chicken counterpart to an important human immune system protein, revised scientists’ assessment of the chicken’s sense of smell, and suggested that the chicken, long used to study gene activity in the earliest stages of life, may provide a good model for studying changes in DNA linked to aging and death.

Other findings from the analysis, reported in the Dec. 9 issue of Nature by the International Chicken Genome Sequencing Consortium, include the identification of genes that affirm the chicken’s value as a model for study of developmental disorders like cleft palate and diseases like muscular dystrophy.

Researchers completed and made available the genetic sequence of the red jungle fowl — a wild ancestor of the domestic chicken whose scientific name is Gallus gallus — in March 2004. The genome provides several firsts: it is the first bird, the first agricultural animal, and the first descendant of the dinosaurs to have its genome sequenced.

The International Chicken Genome Sequencing Consortium is directed by Richard K. Wilson, Ph.D., director of the Genome Sequencing Center at Washington University School of Medicine in St. Louis.

Wilson and other project leaders predict that the chicken genome will help biomedical researchers seeking to better understand the human genome in order to improve diagnosis and treatment of human disease. Another paper appearing in the Dec. 9 Nature found relatively little genetic difference between Gallus gallus and domesticated chicken breeds, highlighting the genome’s potential to aid agricultural scientists trying to improve the chicken as a nutritional resource and to limit the spread of avian flu viruses.

Scientists found the chicken genome has about the same number of genes as the human genome: 20,000-23,000 versus the human genome’s estimated 20,000-25,000 genes. However, those genes are contained in only 1 billion DNA base pairs, a mere third of human DNA’s 2.8 billion base pairs. After confirming the chicken genome’s size, scientists searched for reasons why chickens have less DNA.

“A part of what’s missing is some of the ‘junk’ DNA — the recognizable repetitive content of the chicken genome is only about 10 percent as compared to about 50 percent for humans,” says lead author LaDeana Hillier, senior research scientist at the GSC.

Scientists identified a chicken gene for interleukin 26, an important immune response protein only previously seen in humans. Researchers hope that further study of the chicken’s immune system will lead to the development of better ways to control the spread of viruses, such as the bird flu in Asia. These viruses sometimes jump across species and infect humans.

“With both the human and the chicken genome sequences completed, we can ask more questions about what types of resistance to viral infections and other pathogens are possible for humans and chickens,” Wilson says.

The chicken has traditionally been regarded as having a poor sense of smell, but an assessment of the number of smell receptors in the chicken genome has scientists reconsidering. The total number of receptors doesn’t put the chicken in the same league as olfactory champions like the dog or the mouse, but it may place the chicken’s sense of smell on a par with the human sense of smell. However, a search for taste receptors turned up relatively few results, suggesting chickens have a poor sense of taste.

By function, one area of strong chicken-to-human similarity was in genetic sequences related to early development. Several developmental genes, including genes linked to disorders that cause limb loss or deformity, were found in what the authors call ultraconserved regions—large, identical regions of DNA found in the genomes of chickens, mammals and humans.

“Because it’s so easy to look at and manipulate gene activity as an embryo develops in the egg, scientists often use the chicken in studies of development. The finding that some of these ultraconserved regions are involved in development affirms the chicken as a valuable model for these studies,” Hillier says.

Analysis of the chicken’s telomeres, cap-like structures on the ends of chromosomes, revealed that they are more similar to human telomeres than rodent telomeres. Scientists believe telomeres shorten the DNA slightly every time a cell divides, eventually making it impossible for the cell to divide. This inability to renew through cell division is thought to be a primary component of the structural and functional breakdowns produced by aging.

Increased telomere similarity may mean that the chicken, already a valuable tool for study of the earliest stages of life, also will become useful for study of its final stages.

Wilson compares the chicken genome and other genomes to Rosetta Stones scientists are using to better understand the human genome. As life on Earth evolved over time, genes have been created, kept, discarded or deactivated, and reorganized. At the particular point in evolutionary time over which a species first develops, these processes may have changed a gene in ways that allow scientists to use it to get a better fix on the human version of the gene.

“For every human gene, there’s a gene in another species that’s going to be most helpful in understanding the human version,” Wilson explains. “For some human genes, we might be able to learn more by looking at the genome of the mouse; for others, we might have to look at the version of the gene found in the chicken.”

Based on their initial look at the chicken genome, scientists have suggested that they may need to alter the proposed starting point for as many as 2,000 human genes.

Their analysis showed that chickens and humans share about 60 percent of their genes, as opposed to the approximately 88 percent shared by humans and rodents.

“The chicken is really in an evolutionary sweet spot,” says Wilson. “It’s at just the right evolutionary distance from all the other genomes we already have to provide us with a great deal of fresh insight into the human genome.”

The International Chicken Genome Sequencing Consortium includes scientists from China, Denmark, France, Germany, Japan, Poland, Singapore, Spain, Sweden, Switzerland, the United Kingdom and the United States.

International Chicken Genome Sequencing Consortium. Sequence and analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature, Dec. 9, 2004.

Funding from the National Human Genome Research Institute, Biotechnology and Biological Sciences Research Council, Center for Integrative Genomics Funds, Childcare and Lejeune Foundations, Chinese Academy of Science and Ministry of Science and Technology, Department of Energy, Desiree and Niels Yde Foundation, European Union, European Molecular Biology Laboratory, Fonds Quebecois de la Recherche sur la Nature et les Technologies, Howard Hughes Medical Institute, National Institute for Diabetes and Digestive and Kidney Diseases, National Institutes of Health, National Natural Science Foundation of China, National Science Foundation, Novo Nordisk Foundation, Stowers Institute for Medical Research, Swedish Research Council, Swiss NCRR Frontiers in Genetics, Swiss National Science Foundation, USDA/CSREES National Research Initiative, USDA/CSREES National Animal Genome Research Program, Wallenberg Consortium North and the AgriFunGen program at the Swedish University of Agricultural Sciences, UK Medical Research Council, University of California Presidential Chair Fund, University of Pennsylvania Genomics Institute Award, University of Texas at Arlington, and the Wellcome Trust.