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Updated: Jul 19, 2026
07:09
A Bioinformatics Pipeline for Investigating Molecular Evolution and Gene Expression using RNA-seq
Published on: May 28, 2021
Structural divergence and adaptive evolution in mammalian cytochromes P450 2C
Rute R da Fonseca1, Agostinho Antunes, André Melo
1REQUIMTE, Departamento de Química, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal.
Gene
|October 19, 2006
Summary
Cytochromes P450 (CYPs) enzymes show adaptive evolution, with changes in substrate specificity driven by environmental xenobiotics. Key functional sites involved in substrate entry and active sites reveal signatures of positive selection in the CYP2 family.
Area of Science:
- Biochemistry
- Evolutionary Biology
- Pharmacology
Background:
- Cytochromes P450 (CYPs) are crucial enzymes metabolizing drugs and environmental toxins.
- Their substrate specificity may evolve in response to diverse xenobiotics, impacting human health.
- The CYP2 family is vital for drug metabolism.
Purpose of the Study:
- To investigate functional divergence and selection signatures in mammalian CYP2 genes.
- To understand the evolutionary mechanisms behind CYP substrate specificity diversification.
Main Methods:
- Analysis of mammalian CYP2 gene sequences.
- Identification of functionally divergent sites.
- Detection of positive selection signatures.
Main Results:
- Thirteen functionally divergent sites were identified.
- Eight sites under strong positive selection were found.
- These sites are located in critical functional domains, including the substrate entrance channel and active site.
Conclusions:
- Mammalian CYP2 genes show evidence of adaptive evolution.
- Molecular adaptation plays a significant role in diversifying CYP enzyme substrate specificity.
- Findings offer insights into CYP evolution and drug metabolism.
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