Gene expression profiling of cells, tissues, and developmental stages of the nematode C. elegans.
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Biomedical subjects
Publications and source records attributed to E Sonnhammer.
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The complete genome sequence of the nematode Caenorhabditis elegans provides an excellent basis for studying the distribution and evolution of protein families in higher eukaryotes. Three fundamental questions are as follows: How many paralog clusters exist in one species, how many of these are shared with other species, and how many proteins can be assigned a functional counterpart in other species? We have addressed these questions in a detailed study of predicted membrane proteins in C. elegans and their mammalian homologs. All worm proteins predicted to contain at least two transmembrane segments were clustered on the basis of sequence similarity. This resulted in 189 groups with two or more sequences, containing, in total, 2647 worm proteins. Hidden Markov models (HMMs) were created for each family, and were used to retrieve mammalian homologs from the SWISSPROT, TREMBL, and VTS databases. About one-half of these clusters had mammalian homologs. Putative worm-mammalian orthologs were extracted by use of nine different phylogenetic methods and BLAST. Eight clusters initially thought to be worm-specific were assigned mammalian homologs after searching EST and genomic sequences. A compilation of 174 orthology assignments made with high confidence is presented.
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With the completion of the first phase of the European yeast genome sequencing project, the complete DNA sequence of chromosome III of Saccharomyces cerevisiae has become available (Oliver, S. G., et al., 1992, Nature 357, 38-46). We have tested the predictive power of computer sequence analysis of the 176 probable protein products of this chromosome, after exclusion of six problem cases. When the results of database similarity searches are pooled with prior knowledge, a likely function can be assigned to 42% of the proteins, and a predicted three-dimensional structure to a third of these (14% of the total). The function of the remaining 58% remains to be determined. Of these, about one-third have one or more probable transmembrane segments. Among the most interesting proteins with predicted functions are a new member of the type X polymerase family, a transcription factor with an N-terminal DNA-binding domain related to GAL4, a "fork head" DNA-binding domain previously known only in Drosophila and in mammals, and a putative methyltransferase. Our analysis increased the number of known significant sequence similarities on chromosome III by 13, to now 67. Although the near 40% success rate of identifying unknown protein function by sequence analysis is surprisingly high, the information gap between known protein sequences and unknown function is expected to widen and become a major bottleneck of genome projects in the near future. Based on the experience gained in this test study, we suggest that the development of an automated computer workbench for protein sequence analysis must be an important item in genome projects.