Whole-Genome Identification, Phylogeny, and Evolution of the Cytochrome P450 Family 2 (CYP2) Subfamilies in Birds

Almeida, Daniela; Maldonado, Emanuel; Khan, Imran; Silva, Liliana; Gilbert, M. Thomas P.; Zhang, Guojie; Jarvis, Erich D.; O’Brien, Stephen J.; Johnson, Warren E.; Antunes, Agostinho

doi:10.1093/gbe/evw041

Cited by 22 publications

(35 citation statements)

References 78 publications

(100 reference statements)

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“…The dynamics of gene gain and loss have an important role in the evolution and diversification of gene families [64][65][66][67][68][69][70][71]. These lineage and species-specific changes are important evolutionary mechanisms of adaptation [72][73][74].…”

Section: Dynamic Gene Gain and Loss Shapes Vertebrate Tlr Supergene Fmentioning

confidence: 99%

The Vertebrate TLR Supergene Family Evolved Dynamically by Gene Gain/Loss and Positive Selection Revealing a Host–Pathogen Arms Race in Birds

et al. 2019

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The vertebrate toll-like receptor (TLRs) supergene family is a first-line immune defense against viral and non-viral pathogens. Here, comparative evolutionary-genomics of 79 vertebrate species (8 mammals, 48 birds, 11 reptiles, 1 amphibian, and 11 fishes) revealed differential gain/loss of 26 TLRs, including 6 (TLR3, TLR7, TLR8, TLR14, TLR21, and TLR22) that originated early in vertebrate evolution before the diversification of Agnatha and Gnathostomata. Subsequent dynamic gene gain/loss led to lineage-specific diversification with TLR repertoires ranging from 8 subfamilies in birds to 20 in fishes. Lineage-specific loss of TLR8-9 and TLR13 in birds and gains of TLR6 and TLR10-12 in mammals and TLR19-20 and TLR23-27 in fishes. Among avian species, 5–10% of the sites were under positive selection (PS) (omega 1.5–2.5) with radical amino-acid changes likely affecting TLR structure/functionality. In non-viral TLR4 the 20 PS sites (posterior probability PP > 0.99) likely increased ability to cope with diversified ligands (e.g., lipopolysaccharide and lipoteichoic). For viral TLR7, 23 PS sites (PP > 0.99) possibly improved recognition of highly variable viral ssRNAs. Rapid evolution of the TLR supergene family reflects the host–pathogen arms race and the coevolution of ligands/receptors, which follows the premise that birds have been important vectors of zoonotic pathogens and reservoirs for viruses.

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Section: Dynamic Gene Gain and Loss Shapes Vertebrate Tlr Supergene Fmentioning

confidence: 99%

The Vertebrate TLR Supergene Family Evolved Dynamically by Gene Gain/Loss and Positive Selection Revealing a Host–Pathogen Arms Race in Birds

et al. 2019

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“…For Magellanic penguins, it is unknown whether such polymorphisms or other variations in CYP enzyme profiles exist; however, there is evidence for differences in CYP expression between other bird and penguin species. A study by Almeida and co‐workers (Almeida et al., ) on the genome of a large variety of bird species studying the presence of metabolic enzymes of the CYP2 family on a DNA level revealed a striking difference in the profile between Adelie penguins and Emperor penguins, even though both species live in the same environmental conditions and have a comparable diet. Adelie penguins appeared to have a broad spectrum of CYP2 enzymes, but lacking sufficient CYP2C enzymes, while the Emperor penguin only had three out of twelve CYP2 isoforms tested in the study.…”

Section: Discussionmentioning

confidence: 99%

Application of different pharmacokinetic models to describe and predict pharmacokinetics of voriconazole in magellanic penguins following oral administration

Parsley

Mutlow

Hansted

et al. 2018

Vet Pharm & Therapeutics

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Aspergillosis is a condition causing serious morbidity and mortality in captive penguins and other bird species. It can be treated with antifungal drugs, such as voriconazole. However, the pharmacokinetics of voriconazole are variable between different animal and bird species. Therefore, the pharmacokinetics of voriconazole were investigated in this study in Magellanic penguins. Pharmacokinetic models were constructed and applied to predict the pharmacokinetics of voriconazole during long-term treatment in Magellanic penguins, since the voriconazole treatment duration in chronic aspergillosis cases can last up to several months. Plasma voriconazole concentration-time data from adult Magellanic penguins (Spheniscus magellanicus; n = 15) following a single oral (PO) dose of either 2.5 mg/kg or 5 mg/kg in a herring in three separate study periods 7-12 months apart were collected. Mean plasma voriconazole concentrations were above the targeted MIC for Aspergillus fumigatus for 2 hr following a single 2.5 mg/kg voriconazole dose while the plasma concentrations exceeded the MIC for least 24 hr following a 5 mg/kg dose. Nonlinear mixed-effects modeling was used to fit two pharmacokinetic models, one with first-order and another with saturable elimination, to the single-dose data. Fits were good for both, as long as dose was included as a covariate for the first-order model so that clearance was lower and the half-life longer for animals receiving the 5 mg/kg dose. Although the single-dose data suggested saturated elimination at higher concentrations, the model with saturable elimination did not predict plasma voriconazole concentrations well for a clinical aspergillosis case receiving long-term treatment, possibly because of induction of metabolizing enzymes with chronic exposure. Pharmacokinetic models should accurately predict plasma drug concentrations for different dosage regimens in order to be applicable in the field. Future studies should focus on determining clearance at steady-state to be able to refine the pharmacokinetic models presented here and improve model performance for long-term oral voriconazole administration in Magellanic penguins.

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“…Thus, the contribution of other CYP2 genes or other CYP families may affect the relationship between CYP2D gene number and dietary preferences. A previous study that analyzed the relationship between the number of CYP2 genes and diet in birds discovered that in migratory birds, omnivores had a higher number of CYP2 genes than carnivores and herbivores (Almeida et al., ). In a preliminary analysis using the data from Thomas (), the same trend was observed in mammals (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Complex gene expansion of the CYP2D gene subfamily

Feng

Liu

2018

Ecology and Evolution

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Cytochrome P450 (CYP) superfamily genes encode enzymes that play a role in metabolizing endogenous compounds and in detoxifying exogenous chemicals. The CYP2D subfamily is a member of the CYP2 family, and its gene expansion in herbivores is presumably linked with the need to detoxify abundant plant toxins in the diet, which indicates that CYP2D gene expansion is associated with dietary preferences. To test this hypothesis, the dietary information and CYP2D gene number for 73 vertebrates from different taxonomic groups including 22 mammals, 49 birds, 1 reptile, and 1 amphibian were collected, and correlation analysis and ANOVA were conducted. The results showed that most species (45/73) had only one CYP2D gene, despite their different diets, and dietary preferences were not correlated with CYP2D gene numbers. Specifically, the majority of birds and 7 mammals had only 1 CYP2D gene, and the CYP2D gene number of mammals ranged from 1 to 11, irrespective of their feeding habits. Species with a CYP2D gene number ≥5 included carnivores, herbivores, and omnivores. Furthermore, statistical analyses revealed that no significant correlation existed between dietary preferences and CYP2D gene number, and there was no significant CYP2D gene number variation among species with different dietary preferences, regardless of whether all vertebrates or specific lineages were considered. Furthermore, gene dynamics which indicated by gene duplication events and loss events showed that CYP2D gene number variation had no relationship with diet, suggesting that diet was not a driving force of CYP2D gene expansion and that CYP2D gene expansion was more complex than previously recognized.

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Whole-Genome Identification, Phylogeny, and Evolution of the Cytochrome P450 Family 2 (CYP2) Subfamilies in Birds

Cited by 22 publications

References 78 publications

The Vertebrate TLR Supergene Family Evolved Dynamically by Gene Gain/Loss and Positive Selection Revealing a Host–Pathogen Arms Race in Birds

The Vertebrate TLR Supergene Family Evolved Dynamically by Gene Gain/Loss and Positive Selection Revealing a Host–Pathogen Arms Race in Birds

Application of different pharmacokinetic models to describe and predict pharmacokinetics of voriconazole in magellanic penguins following oral administration

Complex gene expansion of the CYP2D gene subfamily

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