Integrative and comparative genomic studies of seven model avian species. Evolutionary perspectives on gross genomic changes and on G-bands

Genome projects provide resources to study many traits and diseases. Animals may be used as models for processes that are difficult to analyse in humans or may be important agriculturally. Chickens have among the best embryos to study because they are large and easily accessible (by opening an egg), in addition, about 20% of world meat and most egg consumption arises via chicken farming. The genome is attractive to examine because it is small, because there is less 'junk' DNA in birds than mammals. Scientists interested in the genomes of vertebrates would therefore rather look at birds just as most people would rather look for something in a tidy house than a messy one. A description of the chicken genome was announced in 2004 and paved the way to start work on other birds. It is possible to generate genome maps for such birds using available chicken information. An obvious next bird to look at is the turkey, turkey is also of agricultural importance and we are in the advanced stages of making a map for this animal. Other interesting species include ducks; the recent reports both in the popular press and scientific journals have highlighted the fact that ducks are unaffected carriers of bird flu where birds like chickens and turkeys can die from it. Another interesting species is zebra finch. These tiny aviary birds are excellent models for examining brain processes because they 'talk to one another like humans' in a way that few species can. Others include goose (for agricultural reasons), ostrich (evolutionarily, it is very far removed from chicken) and vulture (as the species is endangered and because its chromosomes are very different to other birds). There are many ways in which this so-called 'comparative genomics' can be achieved. In our experience it is best to combine two approaches. The first is to use a laboratory technique (called 'FISH') to light up specific genes in chicken then repeat the experiment in another bird to spot where differences and similarities lie. The second is to use a computer and compare similar gene sequences already established. Genes are located on chromosomes, much in the same way as cities and towns are located on islands and continents. Essential to finding a gene of interest is to have a point of reference that is represented by lateral stripes across the chromosomes (bands), each of which has a unique identification number. In the website dedicated to humans, if you open up the front page (www.ensembl.org/Homo_sapiens/) then you will see, on the left hand side, a diagram of chromosomes, complete with bands. By clicking on one of these chromosomes it is possible to find your gene of interest. If you do the same for chicken (www.ensembl.org/Gallus_gallus/) however then you do see chromosomes but the banding information is absent. Of course you can still find your gene but it is much more difficult. An analogy might be, if you say Edinburgh is about three quarters of the way up the length of the UK, only partial information is given. Saying that Edinburgh is about three quarters of the way up the UK, on the east coast, on the Firth of Forth is much more accurate. We therefore propose to perform experiments that will enable us to add banding information to the chicken web site. With this information we can then ask questions about the nature of the bands themselves. For instance, are the 'dark' bands more gene-poor than the light ones? Does the composition of the building blocks of DNA (called 'bases') differ in dark and light bands and so on. We know that there are differences in mammals but, as yet, have little idea about whether similar situations pertain in birds. Comparisons of mammals and birds will provide further insight into their evolution.

The purpose of this application is to seek funds to develop an accurate cytogenetic map of the chicken and, through 'model hopping,' the turkey, duck, goose, zebra finch, vulture, and ostrich. The draft chicken sequence was published in Nature in 2004 however a complete cytogenetic map, where clones are assigned to G-bands is still required. Accurate assignment of clones to G-bands allows integration of chromosome and sequence and thereby sheds light on the nature of G-bands themselves. This has been done in humans but to date no other animals. Comparative studies of the relationships between two species in different phylogenetic classes (i.e. humans and chickens) will provide an evolutionary perspective on the molecular correlates of G-banding e.g. GC content, CpG island distribution, gene density etc. The availability of comparative maps between chicken and 6 other bird species will allow the transfer of genetic information from chicken to these other birds (expediting mapping studies), it will help to target marker development through prediction of new loci and will allow the tracing of evolutionary phylogenies to provide insight into the conservation and comparative function of sequences among vertebrates. Turkey is a close relative of chicken and thus a prime candidate for comparative functional genomic studies (we have mapped over 200 BACs in this species); duck has received attention in recent months because of its resistant to avian influenza (we have already mapped ~120 clones), zebra finch is an emerging model organism for study of many issues relevant to human health and disease because of its ability to communicate via complex learned vocalisations. Turkey, goose, duck and ostrich are also very important agriculturally while the final species (vulture) is interesting as an endangered species and because it has an atypical avian karyotype. Thus, taken together, mapping efforts in these species represent a major challenge in avian genomics.