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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #169476
Title: THE PLANETARY BIOLOGY OF CYTOCHROME P450 AROMATASES

Author
item GUACHER, ERIC - FND/APPL MOLECULAR EVOL
item GRADDY, LOGAN - DUKE UNIV MED CTR
item LI, TANG - FND/APPL MOLECULAR EVOL
item SIMMEN, ROSALIA - UAMS/ACNC
item SIMMEN, FRANK - UAMS/ACNC
item SCHREIBER, DAVID - FND/APPL MOLECULAR EVOL
item LIBERLES, DAVID - BERGEN CTR/COMPT SCIENCE
item JANIS, CHRISTINE - BROWN UNIVERSITY
item BENNER, STEVEN - UNIV-FLORIDA/GAINESVILLE

Submitted to: BMC Plant Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/17/2004
Publication Date: 8/17/2004
Citation: Guacher, E.A., Graddy, L.G., Li, T., Simmen, R.C., Simmen, F.A., Schreiber, D.R., Liberles, D.A., Janis, C.M., Benner, S.A. 2004. The planetary biology of cytochrome p450 aromatases. BMC Biology. 2(1):19.

Interpretive Summary: We performed a study asking why modern pigs evolved three copies of a particular gene (aromatase) that causes estrogens (female hormones that affect reproduction) to be produced in tissues. To understand why this unique situation occurred (most organism have only one copy of this gene), we employed a combination of new laboratory and computer-based techniques. Our analysis suggests that these three genes arose in pigs as a result of natural selection for animals with larger litters than their ancestors, and this permitted this species to survive the global climatic change that began in the Eocene period of natural history. This research is one of only few examples of a new scientific field referred to as 'planetary biology'.

Technical Abstract: Background Joining a model for the molecular evolution of a protein family to the paleontological and geological records (geobiology), and then to the chemical structures of substrates, products, and protein folds, is emerging as a broad strategy for generating hypotheses concerning function in a post-genomic world. This strategy expands systems biology to a planetary context, necessary for a notion of fitness to underlie (as it must) any discussion of function within a biomolecular system. Results Here, we report an example of such an expansion, where tools from planetary biology were used to analyze three genes from the pig Sus scrofa that encode cytochrome P450 aromatases'enzymes that convert androgens into estrogens. The evolutionary history of the vertebrate aromatase gene family was reconstructed. Transition redundant exchange silent substitution metrics were used to interpolate dates for the divergence of family members, the paleontological record was consulted to identify changes in physiology that correlated in time with the change in molecular behavior, and new aromatase sequences from peccary were obtained. Metrics that detect changing function in proteins were then applied, including KA/KS values and those that exploit structural biology. These identified specific amino acid replacements that were associated with changing substrate and product specificity during the time of presumed adaptive change. The combined analysis suggests that aromatase paralogs arose in pigs as a result of selection for Suoidea with larger litters than their ancestors, and permitted the Suoidea to survive the global climatic trauma that began in the Eocene. Conclusions This combination of bioinformatics analysis, molecular evolution, paleontology, cladistics, global climatology, structural biology, and organic chemistry serves as a paradigm in planetary biology. As the geological, paleontological, and genomic records improve, this approach should become widely useful to make systems biology statements about high-level function for biomolecular systems.