Saccharomyces comparative genomics:
Genes, regulatory motifs, and genome evolution.
Manolis Kellis (Kamvysselis),
Nick Patterson, Bruce Birren, Eric Lander
Center for Genome Research, MIT / Whitehead Institute, 320 Charles St,
Cambridge, MA 02139, USA (manoli@mit.edu)
We have
sequenced the complete genomes of three relatives of S. cerevisiae to depths greater than
7X sequence coverage. Our assemblies contain 95% or more of each species and
overlapping four-way alignments cover 90% of S. cerevisiae. The data can be
obtained freely via the SGD website ./ and at
http://www-genome.wi.mit.edu/seq/Saccharomyces/. The alignments allowed us to
revisit the S. cerevisiae genome. Nearly a tenth of currently annotated S.
cerevisiae
ORFs show an accumulation of frame shift mutations, suggesting they are not
actual genes. We further proposed changed boundaries for ~300 ORFs, the merging
of ~30 pairs of consecutive ORFs and the presence of ~60 novel introns.
Additionally, we identified ~50 novel short ORFs and proposed numerous changes
to the S288C sequence that were confirmed by resequencing. We also used the
alignments for the genome-wide discovery of regulatory motifs. We discovered 72
candidate regulatory elements with strong genome-wide conservation. These
include virtually all previously characterized regulatory motifs and a number
of novel motifs. We assigned a candidate function to the majority of the motifs
discovered based on enrichment in genes of related function, similar expression
and bound by the same transcription factor. Finally, we studied the evolution
of these four closely related species. We observed molecular mechanisms of
rapid protein change, protein family expansion and chromosomal rearrangements.