Co-Authors:
Yanai, I., Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel
Benjamin, H., Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel, Dept. of Physics of Complex Systems, Weizmann Institute of Science, 76100 Rehovot, Israel
Shmoish, M., Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel
Chalifa-Caspi, V., Department of Biological Services, Weizmann Institute of Science, 76100 Rehovot, Israel
Shklar, M., Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel
Ophir, R., Department of Biological Services, Weizmann Institute of Science, 76100 Rehovot, Israel
Bar-Even, A., Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel
Horn-Saban, S., Department of Biological Services, Weizmann Institute of Science, 76100 Rehovot, Israel
Safran, M., Department of Biological Services, Weizmann Institute of Science, 76100 Rehovot, Israel
Domany, E., Dept. of Physics of Complex Systems, Weizmann Institute of Science, 76100 Rehovot, Israel
Lancet, D., Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel
Shmueli, O., Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel
Abstract:
Motivation: Genes are often characterized dichotomously as either housekeeping or single-tissue specific. We conjectured that crucial functional information resides in genes with midrange profiles of expression. Results: To obtain such novel information genome-wide, we have determined the mRNA expression levels for one of the largest hitherto analyzed set of 62839 probesets in 12 representative normal human tissues. Indeed, when using a newly defined graded tissue specificity index τ, valued between 0 for housekeeping genes and 1 for tissue-specific genes, genes with midrange profiles having 0.15 < τ < 0.85 were found to constitute >50% of all expression patterns. We developed a binary classification, indicating for every gene the lB tissues in which it is overly expressed, and the 12 - lB tissues in which it shows low expression. The 85 dominant midrange patterns with lB = 2-11 were found to be bimodally distributed, and to contribute most significantly to the definition of tissue specification dendrograms. Our analyses provide a novel route to infer expression profiles for presumed ancestral nodes in the tissue dendrogram. Such definition has uncovered an unsuspected correlation, whereby de novo enhancement and diminution of gene expression go hand in hand. These findings highlight the importance of gene suppression events, with implications to the course of tissue specification in ontogeny and phylogeny. © The Author 2004. Published by Oxford University Press. All rights reserved.
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