Novel Cytochrome P450, cyp6a17, Is Required for Temperature Preference Behavior in Drosophila

Kang, Jongkyun; Kim, Jaeseob; Choi, Kwang‐Wook

doi:10.1371/journal.pone.0029800

Cited by 32 publications

(27 citation statements)

References 40 publications

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“…However, given that it putatively metabolises a xenobiotic compound, even though that metabolism increases its toxicity, it seems likely that it detoxifies other similar compounds. Cyp6a17 (DS = 3) has characterised roles in pyrethroid insecticide resistance (Battlay et al, 2018; Duneau et al, 2018), but also has a connection to temperature preference behaviour (Chakraborty:2018fh; Kang et al, 2011). This is not the only behavioural phenotype linked to a P450: Cyp6a20 (DS = 3), has a putatively S-class (secondary metabolic) function due to its links to male aggression (Dierick and Greenspan, 2006; Robin et al, 2007; L. Wang et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

Identifying candidate detoxification genes in the ecdysteroid kinase-like (EcKL) and cytochrome P450 gene families inDrosophila melanogasterby integrating evolutionary and transcriptomic data

Scanlan

Battlay

et al. 2020

Preprint

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1 and cytochrome P450 gene families in Drosophila melanogaster by integrating 2 evolutionary and transcriptomic data 3 4Abstract: The capacity to detoxify toxic compounds is essential for adaptation to the 22 ecological niches of many organisms, especially insects. However, detoxification in 23 insects is often viewed through the lens of mammalian detoxification research, even 24 though the organ and enzyme systems involved have diverged for over half a billion 25 years. Phosphorylation is a non-canonical phase II detoxification reaction that, 26 among animals, occurs near exclusively in insects, but the enzymes responsible 27 have never been cloned or otherwise identified. We propose the hypothesis that 28 members of the arthropod-specific ecdysteroid kinase-like (EcKL) gene family 29 encode detoxicative kinases. To test this hypothesis, we annotated the EcKL gene 30 family in 12 species of Drosophila and explored their evolution within the genus. 31 Many ancestral EcKL clades are evolutionarily unstable and have experienced 32 repeated gene gain and loss events, while others are conserved as single copy 33 orthologs. Leveraging multiple published gene expression datasets from D. 34 melanogaster, and using the cytochrome P450s-a canonical detoxification family-35 as a test case, we demonstrate relationships between xenobiotic induction, 36 detoxification tissue-enriched expression and evolutionary instability in the EcKLs 37 and the P450s. We also found previously unreported genomic and transcriptomic 38 variation in a number of EcKLs and P450s associated with toxic stress phenotypes 39 using a targeted phenome-wide association study (PheWAS) approach. Lastly, we 40 devised a systematic method for identifying candidate detoxification genes in large 41 gene families that is concordant with experimentally determined functions of P450 42 genes in D. melanogaster. Applying this method to the EcKLs suggested a 43 significant proportion of these genes play roles in detoxification, and that the EcKLs 44 may constitute a detoxification gene family in insects. Additionally, we estimate that 45 between 11-16 uncharacterised D. melanogaster P450s are strong detoxification 46 candidates. 47 48 Highlights 49 50• The poorly characterised ecdysteroid kinase-like (EcKL) gene family is 51 hypothesised to encode enzymes responsible for detoxification by 52 phosphorylation in insects. 53• An integrative 'detoxification score' method accurately categorises the known 54 functions of a canonical detoxification family, the cytochrome P450s, and 55 suggests many EcKLs are also involved in detoxification. 56• A targeted phenome-wide association study finds novel associations between 57 EcKL/P450 variation and a number of toxic stress phenotypes, such as two 58 unlinked EcKL paralogs that are both associated with developmental 59 methylmercury resistance. 60 61 1983 131 132The identification of detoxification genes and enzymes is an important part of 133 bridging the gap between toxicology, chemical ecology and functional genomics in ...

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Section: Resultsmentioning

confidence: 99%

Identifying candidate detoxification genes in the ecdysteroid kinase-like (EcKL) and cytochrome P450 gene families inDrosophila melanogasterby integrating evolutionary and transcriptomic data

Scanlan

Battlay

et al. 2020

Preprint

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“…For Med pair, there were three cis-genes showing high window F ST ( Ciao1 , Cyp6a17 , and NiPp1 ) and one cis-gene showing high F ST_SNPmax ( spin ). Interestingly, Cyp6a17 encodes a cytochrome P450 protein that is required for temperature preference behavior (Kang et al 2011). Cyp6a17 variants have also been associated with insecticide resistance (Battlay et al 2018; Duneau et al 2018).…”

Section: Resultsmentioning

confidence: 99%

Parallel and Population-specific Gene Regulatory Evolution in Cold-Adapted Fly Populations

Huang

Lack

Hoppel

et al. 2019

Preprint

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17Changes in gene regulation at multiple levels may comprise an important share of the molecular 18 changes underlying adaptive evolution in nature. However, few studies have assayed within-and 19 between-population variation in gene regulatory traits at a transcriptomic scale, and therefore 20 inferences about the characteristics of adaptive regulatory changes have been elusive. Here, we assess 21 quantitative trait differentiation in gene expression levels and alternative splicing (intron usage) 22 between three closely-related pairs of natural populations of Drosophila melanogaster from contrasting 23 thermal environments that reflect three separate instances of cold tolerance evolution. The cold-24 adapted populations were known to show population genetic evidence for parallel evolution at the 25 SNP level, and here we find significant although somewhat limited evidence for parallel expression 26 evolution between them, and less evidence for parallel splicing evolution. We find that genes with 27 mitochondrial functions are particularly enriched among candidates for adaptive expression 28 evolution. We also develop a method to estimate cis-versus trans-encoded contributions to 29 expression or splicing differences that does not rely on the presence of fixed differences between 30 parental strains. Applying this method, we infer important roles of both cis-and trans-regulation 31 among our putatively adaptive expression and splicing differences. The apparent contributions of cis-32 versus trans-regulation to adaptive evolution vary substantially among population pairs, with an 33 Ethiopian pair showing pervasive trans-effects, suggesting that basic characteristics of regulatory 34 evolution may depend on biological context. These findings expand our knowledge of adaptive gene 35 regulatory evolution and our ability to make inferences about this important and widespread process.36 37 50 The level of parallelism for gene expression abundance changes varies across study systems. In some 51 taxa and natural conditions, significantly more genes show parallel changes (repeatedly up-or down-52 regulated in one ecotype relative to the other among independent population pairs) than anti-53 directional changes (Zhao et al. 2015; Hart et al. 2018; Kitano et al. 2018; McGirr and Martin.54 2018). However, some other cases did not show significant parallel patterns, or they even show anti-55 parallel patterns (Derome et al. 2006; Lai et al. 2008; Hanson et al. 2017). The varying degree of 56 parallelism may partly be explained by the level of divergence among ancestors: more closely related 57 ancestors are expected to show a higher degree of parallel genetic evolution underlie similar 58 phenotypic evolution (Conte et al. 2012; Rosenblum et al. 2014). 59 60 Furthermore, gene expression evolution can be caused by the same or different molecular 61 underpinnings. Because of the difficulties of mapping expression QTL, a first step is to classify the 62 expression evolution into two regulatory classes. Cis-regulatory change...

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“…The ISO1 Cyp6a17 gene model is shown in dark blue. As evident here, A4 is lacking Cyp6a17 and might show defects in temperature preference (Kang, et al 2011). Figure S14.…”

Section: Estimating Duplicate Allele Frequenciesmentioning

confidence: 81%

“…For example, 18 genes have been partially deleted in A4 (Table S6). One of these genes, Cyp6a17 is known to affect temperature preference (Kang, et al 2011). Because exons 1 and 2 and intron 1 of the A4 Cyp6a17 are deleted ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Extensive hidden genetic variation shapes the structure of functional elements in Drosophila

Chakraborty

Zhao

Zhang

et al. 2017

Preprint

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Mutations that add, subtract, rearrange, or otherwise refashion genome structure often affect phenotypes, though the fragmented nature of most contemporary assemblies obscure them. To discover such mutations, we assembled the first reference quality genome of Drosophila melanogaster since its initial sequencing. By comparing this genome to the existing D. melanogaster assembly, we create a structural variant map of unprecedented resolution, revealing extensive genetic variation that has remained hidden until now. Many of these variants constitute strong candidates underlying phenotypic variation, including tandem duplications and a transposable element insertion that dramatically amplifies the expression of detoxification genes associated with nicotine resistance. The abundance of important genetic variation that still evades discovery highlights how crucial high quality references are to deciphering phenotypes.

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Novel Cytochrome P450, cyp6a17, Is Required for Temperature Preference Behavior in Drosophila

Cited by 32 publications

References 40 publications

Identifying candidate detoxification genes in the ecdysteroid kinase-like (EcKL) and cytochrome P450 gene families inDrosophila melanogasterby integrating evolutionary and transcriptomic data

Identifying candidate detoxification genes in the ecdysteroid kinase-like (EcKL) and cytochrome P450 gene families inDrosophila melanogasterby integrating evolutionary and transcriptomic data

Parallel and Population-specific Gene Regulatory Evolution in Cold-Adapted Fly Populations

Extensive hidden genetic variation shapes the structure of functional elements in Drosophila

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