Determining the detailed structure and nucleotide sequence of chromosomes from model eucaryotic organisms will be important for understanding how chromosomes function to express, replicate and transmit genetic information. It is anticipated that this information will have important consequences for understanding human chromosome function and gaining knowledge about genetic disease. The yeast, Saccharomyces cerevisiae is one of the most well characterized model organisms and has the advantages of having chromosomes that both are relatively small and behave like the chromosomes of higher organisms. Chromosome I is the smallest S. cerevisiae chromosome and contains a DNA molecule that is only 240 kb making it the smallest normal eucaryotic chromosome yet found. Virtually all of chromosome I is cloned; transcription has been analyzed on two-thirds of it and deletion mutations have been produced in approximately half of its 90-100 genes. In addition, the genetic and physical maps for 90% of the DNA molecule have been aligned and reveal that similar to small human chromosomes, this chromosome undergoes high rates of meiotic recombination. These studies make chromosome I one of the best characterized yeast chromosomes. We now propose to determine the entire nucleotide sequence of chromosome I in collaboration with a consortium of 7 Canadian laboratories as mandated by the International yeast community. Conventional methodology will be used throughout due to the small size of the DNA molecule. Sequences will be analyzed for transcripts, open reading frames, proteins homologies, origins of DNA replication, transposons, etc. Based on the number of genes that currently are mutationally defined on this chromosome, this project will provide fast and important information for relating sequence to biological function and provide a paradigm for the study of other larger chromosomes.
