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Progress in tracing the evolutionary paths of cytochrome P450
1Dept. of Molecular Sciences, University of Tennessee Health Science Center, 858 Madison Ave., Suite G01, Memphis, TN 38163, USA. dnelson@uthsc.edu
Biochimica Et Biophysica Acta
|August 26, 2010
Summary
The cytochrome P450 (CYP) gene family is rapidly expanding, with over 12,000 named sequences. Establishing clear nomenclature, especially using orthology and synteny, is crucial for understanding P450 evolution across diverse phyla.
Area of Science:
- Genomics and Bioinformatics
- Evolutionary Biology
- Biochemistry
Background:
- The cytochrome P450 (CYP) superfamily is a vast group of enzymes involved in diverse metabolic processes.
- Current named CYP sequences exceed 12,456, with an additional 6,000 known but unnamed sequences.
- The increasing number of sequenced genomes necessitates robust strategies for managing and naming CYP sequences.
Purpose of the Study:
- To summarize the current state of cytochrome P450 sequence accumulation across different phyla.
- To discuss nomenclature challenges and propose solutions as genome sequencing accelerates.
- To explore the evolutionary history and functional roles of CYP genes, particularly in animals and fungi.
Main Methods:
- Analysis of accumulated cytochrome P450 sequence data.
- Application of orthology as a guiding principle for naming CYP genes across related genomes.
- Utilizing synteny for deep-time evolutionary studies of P450s in animals.
- Employing the concept of sequence space saturation to assess knowledge completeness.
Main Results:
- Over 12,456 cytochrome P450s are named, with ~6,000 more awaiting naming.
- Orthology is proposed as the primary naming principle for vertebrates, with 19 CYP families identified.
- Variable gene clusters in CYP2, CYP3, and CYP4 families present naming challenges due to lack of 1:1 orthologs.
- Synteny analysis supports tracing the evolutionary origins of animal CYP clans.
- Sequence space saturation estimates indicate varying levels of knowledge completeness across phyla.
- A significant proportion (25-33%) of P450s in filamentous fungi are involved in secondary metabolite gene clusters.
Conclusions:
- Nomenclature strategies, including orthology and synteny, are essential for organizing the expanding cytochrome P450 sequence database.
- Understanding P450 evolution requires integrating genomic data with evolutionary principles.
- Filamentous fungi exhibit specialized P450 roles in secondary metabolism, highlighting phylum-specific adaptations.
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