Nature 423, 241-254 (15 May 2003) | doi:10.1038/nature01644; Received 27 February 2003; Accepted 1 April 2003

Sequencing and comparison of yeast species to identify genes and regulatory elements

Manolis Kellis1,2, Nick Patterson1, Matthew Endrizzi1, Bruce Birren1 & Eric S. Lander1,3

  1. Whitehead/MIT Center for Genome Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
  2. Department of Computer Science and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

Correspondence to: Manolis Kellis1,2Eric S. Lander1,3 Correspondence and requests for materials should be addressed to M.K. (Email: or E.S.L. (Email: GenBank accession numbers are AABY01000000 for S. paradoxus, AABZ01000000 for S. mikatae, and AACA01000000 for S. bayanus.


Identifying the functional elements encoded in a genome is one of the principal challenges in modern biology. Comparative genomics should offer a powerful, general approach. Here, we present a comparative analysis of the yeast Saccharomyces cerevisiae based on high-quality draft sequences of three related species (S. paradoxus, S. mikatae and S. bayanus). We first aligned the genomes and characterized their evolution, defining the regions and mechanisms of change. We then developed methods for direct identification of genes and regulatory motifs. The gene analysis yielded a major revision to the yeast gene catalogue, affecting approximately 15% of all genes and reducing the total count by about 500 genes. The motif analysis automatically identified 72 genome-wide elements, including most known regulatory motifs and numerous new motifs. We inferred a putative function for most of these motifs, and provided insights into their combinatorial interactions. The results have implications for genome analysis of diverse organisms, including the human.