A Revised Evolutionary History of the CYP1A Subfamily: Gene Duplication, Gene Conversion, and Positive Selection

Abstract

Running header: Recombination and selection in tetrapod CYP1AsKey words: Cytochrome P450, gene conversion, gene duplication, chicken, mammalian Abbreviations:Page 1 of 32 JME-2005-00134 ABSTRACTMembers of cytochrome P450 subfamily 1A (CYP1As) are involved in detoxification and bioactivation of common environmental pollutants. Understanding the functional evolution of these genes is essential to predicting and interpreting species differences in sensitivity to toxicity by such chemicals. The CYP1A gene subfamily comprises a single ancestral representative in most fish species and two paralogs in higher vertebrates, including birds and mammals.Phylogenetic analysis of complete coding sequences suggests that mammalian and bird paralog pairs (CYP1A1/2 and CYP1A4/5, respectively) are the result of independent gene duplication events. However, comparison of vertebrate genome sequences revealed that CYP1A genes lie within an extended region of conserved fine-scale synteny, suggesting that avian and mammalian CYP1A paralogs share a common genomic history. Algorithms designed to detect recombination between nucleotide sequences indicate that gene conversion has homogenized most of the length of the chicken CYP1A genes, as well as the 5' end of mammalian CYP1As.Together, these data indicate that avian and mammalian CYP1A paralog pairs resulted from a single gene duplication event and that extensive gene conversion is responsible for the exceptionally high degree of sequence similarity between CYP1A4 and CYP1A5. Elevated nonsynonymous/synonymous substitution ratios within a putatively unconverted stretch of ~250 bp suggests that positive selection may have reduced the effective rate of gene conversion in this region, which contains two substrate recognition sites. This work significantly alters our understanding of functional evolution in the CYP1A subfamily, suggesting that gene conversion and positive selection have been the dominant processes of sequence evolution.

Molecular phylogenies and evolutionary behavior of AhR (aryl hydrocarbon receptor) pathway genes in aquatic animals: Implications for the toxicology mechanism of some persistent organic pollutants (POPs)

“…In addition, compare the d N value between CYP1A1 and CYP1A2 in mammal, we can find that d N value of CYP1A2 (0.158 ± 0.015) is bigger than CYP1A1 (0.125 ± 0.015), and mammal CYP1A2 play an important role in mediating POPs toxicity, therefore, we can suppose that CYP1A2 maybe takes place a greater adaptive evolution than CYP1A1. Surprisingly, this gene is not like other genes in the AhR pathway, the value of d N /d S > 1, calculated using the d N and d S value (Tables 2 and 3), consistent with the results of Goldstone and Stegeman (2006), suggesting that gene conversion and positive selection may have been the dominant processes of sequence evolution, and there may be an adaptive evolution on this gene. This may be because the evolutionary history of the CYP1A superfamily appears to be extremely complex; the reason is that gene and genome duplication, gene amplification and conversion, gene structure rearrangements, gene loss, horizontal gene transfer, and convergent evolution all contribute to the evolution of CYP1A (Werck-Reichhart and Feyereisen, 2000).…”

Structural Characterization of the Complex between α-Naphthoflavone and Human Cytochrome P450 1B1

“…This high degree of conservation is generally not seen for xenobiotic metabolizing P450s in family 2, where the gain and loss of genes through gene duplication and divergence during evolution has led to extensive structural and functional diversity for their active site cavities. In contrast, a single CYP1B1 gene is generally seen in vertebrate genomes (19,20).…”

Cytochrome P450 1A-Dependent Activities in Deer, Cattle and Horses

“…The CYP1A subfamily has a broad affinity for polycyclic aromatic hydrocarbons, heterocyclic amines, endogenous substances and naturally occurring chemicals. Moreover, it plays important roles in both mediating and mitigating the biological effects of these chemicals and can determine susceptibility to toxicity or disease [4,5,7,27].…”