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Physiol. Genomics 38: 1-6, 2009. First published April 14, 2009; doi:10.1152/physiolgenomics.90411.2008
1094-8341/09 $8.00
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Received 9 January 2009; accepted in final form 9 April 2009.
Physiological Genomics 38:1-6 (2009)
1094-8341/09 $8.00 © 2009 American Physiological Society

Call For Papers: Comparative Genomics

Lung evolution as a cipher for physiology

J. S. Torday and V. K. Rehan

Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California

In the postgenomic era, we need an algorithm to readily translate genes into physiologic principles. The failure to advance biomedicine is due to the false hope raised in the wake of the Human Genome Project (HGP) by the promise of systems biology as a ready means of reconstructing physiology from genes. like the atom in physics, the cell, not the gene, is the smallest completely functional unit of biology. Trying to reassemble gene regulatory networks without accounting for this fundamental feature of evolution will result in a genomic atlas, but not an algorithm for functional genomics. For example, the evolution of the lung can be "deconvoluted" by applying cell-cell communication mechanisms to all aspects of lung biology development, homeostasis, and regeneration/repair. Gene regulatory networks common to these processes predict ontogeny, phylogeny, and the disease-related consequences of failed signaling. This algorithm elucidates characteristics of vertebrate physiology as a cascade of emergent and contingent cellular adaptational responses. By reducing complex physiological traits to gene regulatory networks and arranging them hierarchically in a self-organizing map, like the periodic table of elements in physics, the first principles of physiology will emerge.

evolutionary biology; gene regulatory network; cell-cell communication; functional genomics; systems biology






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