Functional Genomics

In 1996, 92 collaborating laboratories in the USA, Canada, the UK and Japan published the complete sequence of the S. cerevisiae genome (Goffeau et al., 1996). This opened up research on how genetic instructions specify a eukaryotic cell, heralding the era of comparative genomics—comparing sequences between different species—and to learn about the basic mechanisms of life that could lead to understanding how genes cause diseases and of finding rationales for treatment. Some examples of spin-offs from the yeast genome sequence are given below.

The 12 million bases in the yeast genome predicted 6213 protein-encoding genes, of which 3470 genes (56%) have homologues in other organisms. The remaining 2743 genes lack identifiable homologues in any organism. When these genes were compared with genes from 13 species of yeast, 1712 genes showed homologues, indicating their common function in this group of organisms. Among the conserved genes are those involved in cell wall biosynthesis and the pheromone response. About 78% of the genes are assigned to biological

Figure 6.11 Components of the mitochondrial protein import machinery. Precursor proteins undergo unfolding in the presence of heat shock protein-70 and mitochondrial import stimulating factor (MSF) proteins. The mitochondrial import receptor complex binds the positively charged N-terminal signal sequence before the protein is transferred to the "Tom" complex in the outer membrane (OM). The protein is transferred to the components of the "Tim" complex in the inner membrane (IM), which pulls it into the matrix where it is folded in the presence of chaperone proteins (mitochondrial heat shock protein-70 and Gro-related protein-E). Once folded, matrix-processing peptidase (MPP) cleaves the signal peptide. Reproduced from Figure 1 in Schatz, G. (1996), J. Biol. Chem. 271:31763-31766. With permission from American Society for Biochemistry and Molecular Biology.

Figure 6.11 Components of the mitochondrial protein import machinery. Precursor proteins undergo unfolding in the presence of heat shock protein-70 and mitochondrial import stimulating factor (MSF) proteins. The mitochondrial import receptor complex binds the positively charged N-terminal signal sequence before the protein is transferred to the "Tom" complex in the outer membrane (OM). The protein is transferred to the components of the "Tim" complex in the inner membrane (IM), which pulls it into the matrix where it is folded in the presence of chaperone proteins (mitochondrial heat shock protein-70 and Gro-related protein-E). Once folded, matrix-processing peptidase (MPP) cleaves the signal peptide. Reproduced from Figure 1 in Schatz, G. (1996), J. Biol. Chem. 271:31763-31766. With permission from American Society for Biochemistry and Molecular Biology.

Unknown process

Figure 6.12 Distribution of yeast genes in different biological processes. A single gene may participate in more than one cellular process. Numbers were compiled from Gene Ontology (GO) resources (http://www.geneontology.org).

processes based on sequence homology, genetic and biochemical evidences (Figure 6.12). For the first time, the availability of a complete sequence of an eukaryotic organism accelerated the discovery and use of novel experimental approaches to understand gene function described in the next sections.

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