Bonnie Berger


Whole-genome comparative annotation and regulatory motif discovery in multiple yeast species

Manolis Kellis (Kamvysselis), Nick Patterson , Bruce Birren , Bonnie Berger, and Eric Lander


With the availability of complete sequences for a number of model organisms, comparative analysis becomes an invaluable tool for understanding genomes. Complete genomes allow for global views and multiple genomes increase predictive power. We have sequenced the complete genomes of S. paradoxus, S. bayanus, and S. mikatae and compared these three yeast species to their close relative, S. cerevisiae. Genome-wide comparative analysis allowed the identification of functionally important sequences, both coding and non-coding, through sequence conservation among all four species. We present methods for the automatic comparative annotation of multiple genomes and the determination of orthologous genes and intergenic regions. We have used the comparison for the exhaustive discovery of non-coding sequence motifs that are involved in controlling gene expression in yeast. We discovered virtually all previously known DNA regulatory motifs, as well as several novel, non-coding sequence motifs that correlate strongly with data from large-scale expression and immunoprecipitation experiments. These regulatory elements were detected on the basis of conservation alone, without relying on previously known groups of co-regulated genes. Our results demonstrate that an entirely automatic genome-wide discovery of regulatory motifs is possible without using data from gene expression or transcription factor binding experiments. Our findings are validated by the extensive experimental knowledge in yeast, confirming their applicability to other genomes.