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conservation categories: full , partial , split , or no conservation of coex-
pression. This approach can also be extended to study the higher-order
correlations between groups of functionally linked genes, providing a
more global view of the conserved and diverged parts of the transcription
programs. 53
Using the DCA, we systematically compared the transcription pro-
gram of the fungal pathogen Candida albicans with that of S. cerevisiae . 53
Many of the differences we identified are related to the differential
requirement for mitochondrial function in the two yeasts. In rich
medium, S. cerevisiae prefers to grow anaerobically and therefore down-
regulates mitochondrial ribosomal protein (MRP) genes; in contrast, in
C. albicans these genes are coexpressed with other genes required for
growth (such as ribosomal genes), since it usually requires mitochondr-
ial functions that use oxygen for its metabolism. While no overrepre-
sented sequence was connected to the S. cerevisiae MRP genes, in
C. albicans the MRP genes were clearly associated with an overrepresented
upstream sequence motif (AATTTT). This sequence was previously
implicated in the regulation of rRNA processing genes in S. cerevisiae ,
although its functional role was not demonstrated experimentally.
Experimental work 54 showed that the AATTTT motif is indeed a cis-
regulatory element of MRP genes in C. albicans. Examining the appearance
of this motif in more detail, we found that its position relative to the
ORF start codon is highly conserved in both S. cerevisiae and C. albi-
cans , as well as in nine other sequenced yeast species that are considered
to be intermediate in the evolution between S. cerevisiae and C. albicans .
In all species examined, the AATTTT motif is significantly overrepre-
sented in genes involved in rRNA processing. Strikingly, its over-repre-
sentation in MRP promoters was found in all genomes that diverged
from the S. cerevisiae lineage prior to the whole-genome duplication
event. Thus, it appears that the emergence of anaerobic growth capac-
ity in yeast is associated with a global rewiring of its transcriptional net-
work involving dozens of MRP genes which lost a specific regulatory
motif. Our results provide further support for the (old) idea 55 that gene
duplication can facilitate the evolution of new function not only by spe-
cialization of coding sequences, but also by facilitating the evolution of
gene expression.
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