. Comparing genomic expression patterns across species identifies shared transcriptional profile in aging. Nat Genet. 2004 Feb;36(2):197-204. PubMed.

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  1. This paper describes a new bioinformatics method for comparing gene expression patterns across species by comparing the results of diverse DNA microarray experiments. The authors exemplify the power of this approach by analyzing gene expression changes associated with aging in two highly divergent animals, C. elegans and Drosophila. Groups of orthologous genes involved in mitochondrial metabolism, catabolism, repair processes, and cellular transport show similar age-related changes in the two organisms. The authors additionally show that transcriptional responses of worms and flies to oxidative stress and heat correlate with aging-related responses, solidifying the link between oxidative stress and aging. A new finding was the suppression of genes encoding transporter-ATPases, which may compromise neuronal and secretory processes in aged animals. These findings suggest that there may be phylogenetic conservation of some gene expression programs associated with aging.

    Although orthologous genes corresponding to functional categories (known as gene ontology categories) were similarly regulated in aging Drosophila and C. elegans, the magnitudes of the expression changes were generally small. This highlights an important issue, which is the biological significance of modest expression changes affecting many related genes. An emerging theme in bioinformatics is that relatively modest expression changes in multiple members of an interacting gene group may be biologically important. An example of this phenomenon was recently reported for diabetes, in which multiple genes that mediate energy metabolism exhibit modestly reduced expression. The authors also demonstrated that their large-scale genomic comparison method could be used to identify conserved gene expression programs associated with other biological processes, including larval development, meiosis, and RNA degradation. Hence, it can be anticipated that comparative functional genomics will be an incisive tool for resolving conserved genetic programs corresponding to a variety of physiological and pathological processes. This approach should be facilitated by the expanding database of microarray results and improved statistical methods for evaluating such data.

    View all comments by Bruce Yankner

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