Influence du dosage de l'allèle non permissif du gène ref(2)P de la Drosophile sur les souches sensibles du virus sigma

Nakamura, Nori

doi:10.1007/bf00268264

Cited by 11 publications

(12 citation statements)

References 4 publications

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“…Second, we can only estimate the amount of genetic variation explained in inbred lines, and this can only be directly extrapolated to outcrossed populations if all the genes affecting resistance are additive. Unfortunately, we cannot estimate the importance or direction of this bias as we only used inbred lines (the only one of the three genes for which levels of dominance has been investigated is ref(2)P , where heterozygotes have intermediate levels of resistance when injected with the virus [29]). However, the bias could be substantial if we make the extreme assumptions about dominance.…”

Section: Resultsmentioning

confidence: 99%

Genome-Wide Association Studies Reveal a Simple Genetic Basis of Resistance to Naturally Coevolving Viruses in Drosophila melanogaster

Magwire¹,

Fabian²,

Schweyen³

et al. 2012

PLoS Genet

156

237

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Variation in susceptibility to infectious disease often has a substantial genetic component in animal and plant populations. We have used genome-wide association studies (GWAS) in Drosophila melanogaster to identify the genetic basis of variation in susceptibility to viral infection. We found that there is substantially more genetic variation in susceptibility to two viruses that naturally infect D. melanogaster (DCV and DMelSV) than to two viruses isolated from other insects (FHV and DAffSV). Furthermore, this increased variation is caused by a small number of common polymorphisms that have a major effect on resistance and can individually explain up to 47% of the heritability in disease susceptibility. For two of these polymorphisms, it has previously been shown that they have been driven to a high frequency by natural selection. An advantage of GWAS in Drosophila is that the results can be confirmed experimentally. We verified that a gene called pastrel—which was previously not known to have an antiviral function—is associated with DCV-resistance by knocking down its expression by RNAi. Our data suggest that selection for resistance to infectious disease can increase genetic variation by increasing the frequency of major-effect alleles, and this has resulted in a simple genetic basis to variation in virus resistance.

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Section: Resultsmentioning

confidence: 99%

Genome-Wide Association Studies Reveal a Simple Genetic Basis of Resistance to Naturally Coevolving Viruses in Drosophila melanogaster

Magwire¹,

Fabian²,

Schweyen³

et al. 2012

PLoS Genet

156

237

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“…The loss of function in the p od1 and p od3 mutants could be due to the deletion of the C-terminal domain of the protein and also to a lack of ref(2)P gene products. Indeed, the very small detectable amounts of the Ref 2P protein should have been sufficient to produce a null phenotype because of the dosage effect on virus multiplication described for the activity of the restrictive ref(2)P alleles (16). In contrast, the mRNA and the protein were found in normal amounts in the p od2 allele mutated in exon 1.…”

Section: Discussionmentioning

confidence: 99%

“…(iv) The interactions involve both the permissive and the restrictive alleles, which are codominant, and their products compete with one another to act on the virus. In a heterozygous strain, the presence of a permissive allele counteracts the activity of a restrictive one (16). (v) A dosage effect on virus replication can be seen in the number of the restrictive ref (2)P gene copies expressed at the locus (16).…”

mentioning

confidence: 99%

“…In a heterozygous strain, the presence of a permissive allele counteracts the activity of a restrictive one (16). (v) A dosage effect on virus replication can be seen in the number of the restrictive ref (2)P gene copies expressed at the locus (16). Protein-protein interactions have been observed at the molecular level.…”

mentioning

confidence: 99%

“…The frequencies of CO 2 -sensitive flies among offspring having different genotypes were compared. The assay methods and calculations have been described previously (8,16).…”

mentioning

confidence: 99%

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Localization of domains within the Drosophila Ref(2)P protein involved in the intracellular control of sigma rhabdovirus multiplication

Wyers

Petitjean

Dru

et al. 1995

J Virol

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The ref(2)P gene of Drosophila melanogaster interferes with sigma rhabdovirus multiplication. This gene is highly variable, and the different alleles are considered permissive or restrictive according to their effects on virus replication. In all cases, the mechanisms involve intracellular interactions between the sigma virus and Ref(2)P proteins. We showed that the N-terminal domain of the Ref(2)P protein was required for its activity in vivo. The protein was inactive in the null p od2 mutant when its first 82 amino acids were deleted. The p ⌬n gene was constructed so that the first 91 amino acids coded for by the restrictive alleles could be expressed in vivo. It was active in a transformed line. This sequence was sufficient to impart a restrictive phenotype to an adult D. melanogaster fly after it was injected with the virus. However, the truncated protein expressed by p ⌬n did not have an effect on the hereditary transmission of the sigma virus to the offspring of the infected flies, even though it contained the restriction site. The native Ref(2)P protein has been previously shown to have conformation-dependent epitopes common with some of those of the viral N protein. We demonstrated the following. (i) These epitopes were found in a domain of the Ref(2)P protein distinct from the site involved in restriction. (ii) They were modified in the N protein of the haP7 sigma virus mutant selected as being adapted to the restrictive alleles of the ref(2)P gene; only one mutation in the N gene, leading to an amino acid substitution, distinguished the haP7 mutant from the original virus. (iii) The virus strains partially or totally adapted to the effects of the full restrictive protein expressed by p p were always found to multiply to a lesser extent in the presence of the protein expressed by p ⌬n. These data suggest that two distinct domains of the Ref(2)P protein are involved in the control of sigma virus multiplication.

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Molecular analysis of ref(2)P, a Drosophila gene implicated in sigma rhabdovirus multiplication and necessary for male fertility.

et al. 1989

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The ref(2)P gene of Drosophila melanogaster is implicated in sigma rhabdovirus multiplication. A permissive allele was cloned and sequenced. The structural gene (3.1 kbp) is divided into three exons. The mRNAs are heterogeneous in size. They differ only in the 5′ end of the first exon. The sequence upstream of the short mRNAs contains classical promoter elements. No TATA and CAAT boxes are appropriately positioned upstream of the initiation sites of the long mRNAs, but several repeats, palindromic sequences and inverted CAAT boxes are present. These observations, together with the tissue‐dependent distribution of short and long transcripts, support the hypothesis of the existence of at least two classes of genuine initiation sites. The long size of the untranslated leader RNA region suggests a control of gene expression at the translation level. The same translation product of 599 amino acids (76.3 kd) is predicted for all mRNAs, but the in vitro translation product migrates in SDS‐PAGE with a higher apparent mol. wt (115‐125 kd). The putative ref(2)P protein contains internal repeats, PEST regions which may be signals for protein degradation, and interesting structural motifs such as zinc finger and amphiphilic helices. These later motifs could be mitochondrial pre‐sequences. The degeneration of mitochondria is observed in the spermatids of sterile male flies homozygous for the loss‐of‐function alleles. The amino acid sequence of the ref(2)P product shows no homology with any known protein from the data banks.

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Influence du dosage de l'allèle non permissif du gène ref(2)P de la Drosophile sur les souches sensibles du virus sigma

Cited by 11 publications

References 4 publications

Genome-Wide Association Studies Reveal a Simple Genetic Basis of Resistance to Naturally Coevolving Viruses in Drosophila melanogaster

Genome-Wide Association Studies Reveal a Simple Genetic Basis of Resistance to Naturally Coevolving Viruses in Drosophila melanogaster

Localization of domains within the Drosophila Ref(2)P protein involved in the intracellular control of sigma rhabdovirus multiplication

Molecular analysis of ref(2)P, a Drosophila gene implicated in sigma rhabdovirus multiplication and necessary for male fertility.

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