scholarly journals Functional interactions between unlinked muscle genes within haploinsufficient regions of the Drosophila genome.

Genetics ◽  
1988 ◽  
Vol 119 (1) ◽  
pp. 105-121
Author(s):  
T Homyk ◽  
C P Emerson
Keyword(s):  
Muscle Development ◽  
Gene Copy Number ◽  
Large Family ◽  
Mutant Gene ◽  
Genetic Interactions ◽  
Gene Copy ◽  
Drosophila Genome ◽  
Gene Products ◽  
New Genes ◽  
Allele Specific

Abstract Mutations in 13 genes affecting muscle development in Drosophila have been examined in pairwise combinations for evidence of genetic interactions. Heterozygous combinations of mutations in five genes, including the gene coding for myosin heavy chain, result in more severe phenotypes than respective single heterozygous mutant controls. The various mutant interactions include examples showing allele-specific intergenic interactions, gene specific interactions, and allele-specific intragenic complementations, suggesting that some interactions result from the manner in which mutant gene products associate. Interactions that result from alterations in "+" gene copy number were also uncovered, suggesting that normal myofibril development requires that the relative amounts of respective gene products produced be tightly regulated. The importance of the latter parameter is substantiated by the finding that all five interacting loci map to disperse haploinsufficient or haplolethal regions of the genome. The implications of the present findings are discussed in relation to pursuing the phenomena involving genetic interactions to identify new genes encoding interacting myofibrillar proteins, to examine the nature of intermolecular interactions in mutant and normal development and to decipher the quantitative and temporal regulation of a large family of functionally related gene products.

scholarly journals RPW8/HR Repeats Predict NLR-dependent Hybrid Performance

2019 ◽  
Author(s):  
Cristina A. Barragan ◽  
Rui Wu ◽  
Sang-Tae Kim ◽  
Wanyan Xi ◽  
Anette Habring ◽  
...  
Keyword(s):  
Genetic Interaction ◽  
Gene Copy Number ◽  
Gene Clusters ◽  
Gene Copy ◽  
Hybrid Necrosis ◽  
Resistance Proteins ◽  
Broad Spectrum Resistance ◽  
Structural Differences ◽  
Allele Specific ◽  
Complex Manner

SummaryHybrid offspring can look very different from their parents, including having greatly increased or decreased fitness. In many plant species, conflicts between divergent elements of the immune system can cause hybrids to express autoimmunity, a generally deleterious syndrome known as hybrid necrosis. We are investigating multiple hybrid necrosis cases in Arabidopsis thaliana that are caused by allele-specific interactions between different variants at two unlinked resistance (R) gene clusters. One is the RESISTANCE TO PERONOSPORA PARASITICA 7 (RPP7) cluster, which encodes an intracellular nucleotide binding site-leucine rich repeat (NLR) immune receptors that confer strain-specific resistance to oomycetes. The other is the RESISTANCE TO POWDERY MILDEW 8 (RPW8)/HOMOLOG OF RPW8 (HR) locus, which encodes atypical resistance proteins that can confer broad-spectrum resistance to filamentous pathogens. There is extensive structural variation in the RPW8/HR cluster, both at the level of gene copy number and at the level of C-terminal protein repeats of unknown function. We demonstrate that the number of RPW8/HR repeats correlate, albeit in a complex manner, with the severity of hybrid necrosis when these alleles are combined with specific RPP7 variants. This observation suggests that gross structural differences, rather than individual amino acid polymorphisms, guide the genetic interaction between RPW8/HR and RPP7 alleles. We discuss these findings in light of the similarity of RPW8/HR proteins with pore-forming toxins, MLKL and HET-S, from mammals and fungi.

scholarly journals From Global to Local—New Insights into Features of Pyrethroid Detoxification in Vector Mosquitoes

Insects ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 276
Author(s):  
William C. Black ◽  
Trey K. Snell ◽  
Karla Saavedra-Rodriguez ◽  
Rebekah C. Kading ◽  
Corey L. Campbell
Keyword(s):  
Pyrethroid Resistance ◽  
Regulation Of Gene Expression ◽  
Gene Copy Number ◽  
Resistance Mechanisms ◽  
Gene Copy ◽  
Tropical Regions ◽  
New Genes ◽  
Oxidation Reduction ◽  
Cellular Pathways ◽  
Post Transcriptional Regulation

The threat of mosquito-borne diseases continues to be a problem for public health in subtropical and tropical regions of the world; in response, there has been increased use of adulticidal insecticides, such as pyrethroids, in human habitation areas over the last thirty years. As a result, the prevalence of pyrethroid-resistant genetic markers in natural mosquito populations has increased at an alarming rate. This review details recent advances in the understanding of specific mechanisms associated with pyrethroid resistance, with emphasis on features of insecticide detoxification and the interdependence of multiple cellular pathways. Together, these advances add important context to the understanding of the processes that are selected in resistant mosquitoes. Specifically, before pyrethroids bind to their targets on motoneurons, they must first permeate the outer cuticle and diffuse to inner tissues. Resistant mosquitoes have evolved detoxification mechanisms that rely on cytochrome P450s (CYP), esterases, carboxyesterases, and other oxidation/reduction (redox) components to effectively detoxify pyrethroids to nontoxic breakdown products that are then excreted. Enhanced resistance mechanisms have evolved to include alteration of gene copy number, transcriptional and post-transcriptional regulation of gene expression, as well as changes to cellular signaling mechanisms. Here, we outline the variety of ways in which detoxification has been selected in various mosquito populations, as well as key gene categories involved. Pathways associated with potential new genes of interest are proposed. Consideration of multiple cellular pathways could provide opportunities for development of new insecticides.

scholarly journals Analysis of CYP2D6 Allele Frequencies and Identification of Novel SNPs and Sequence Variations in Sardinians

ISRN Genetics ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Matteo Falzoi ◽  
Luigi Pira ◽  
Paolo Lazzari ◽  
Luca Pani
Keyword(s):  
Enzyme Level ◽  
Gene Copy Number ◽  
Drug Level ◽  
Caucasian Population ◽  
Allele Frequencies ◽  
Gene Copy ◽  
Sequencing Analysis ◽  
Gene Deletions ◽  
Allele Specific ◽  
Dna Sequencing Analysis

The CYP2D6 enzyme is involved in the metabolism of many commonly prescribed drugs. The presence of polymorphisms in the CYP2D6 gene may modulate the enzyme level and activity affecting individual responses, to pharmacological treatment in drug level, response and adverse reactions. Aims. This study aimed to analyze the determination of allele frequencies in Sardinians and the comparison to frequencies found in the Caucasian Population. Methods and Materials. We used a Long PCR strategy coupled to direct genomic DNA sequencing analysis. An amplification allele-specific was carried out to infer the correct allelic phase. The TaqMan Gene Copy Number Assay (Applied Biosystems) was used to verify the presence of gene deletions/multiplications. Results and Conclusions. Our results indicated that CYP2D6 allele frequencies in Sardinians differed from those previously detected in the Caucasian Population. Moreover, three new SNPs and four novel haplotypes were identified.

scholarly journals Genetic evidence for functional interactions between actin noncomplementing (Anc) gene products and actin cytoskeletal proteins in Saccharomyces cerevisiae.

Genetics ◽  
1993 ◽  
Vol 135 (2) ◽  
pp. 275-286
Author(s):  
D B Vinh ◽  
M D Welch ◽  
A K Corsi ◽  
K F Wertman ◽  
D G Drubin
Keyword(s):  
Synthetic Lethality ◽  
Binding Protein ◽  
Cytoskeletal Proteins ◽  
Genetic Interactions ◽  
Null Alleles ◽  
Actin Binding ◽  
Gene Products ◽  
Actin Binding Protein ◽  
Functional Interactions ◽  
Allele Specific

Abstract We describe here genetic interactions between mutant alleles of Actin-NonComplementing (ANC) genes and actin (ACT1) or actin-binding protein (SAC6, ABP1, TPM1) genes. The anc mutations were found to exhibit allele-specific noncomplementing interactions with different act1 mutations. In addition, mutant alleles of four ANC genes (ANC1, ANC2, ANC3 and ANC4) were tested for interactions with null alleles of actin-binding protein genes. An anc1 mutant allele failed to complement null alleles of the SAC6 and TPM1 genes that encode yeast fimbrin and tropomyosin, respectively. Also, synthetic lethality between anc3 and sac6 mutations, and between anc4 and tpm1 mutations was observed. Taken together, the above results strongly suggest that the ANC gene products contribute to diverse aspects of actin function. Finally, we report the results of tests of two models previously proposed to explain extragenic noncomplementation.

scholarly journals Collateral Toxicity Limits the Evolution of Bacterial Release Factor 2 toward Total Omnipotence

2020 ◽  
Vol 37 (10) ◽  
pp. 2918-2930
Author(s):  
Hind Abdalaal ◽  
Shreya Pundir ◽  
Xueliang Ge ◽  
Suparna Sanyal ◽  
Joakim Näsvall
Keyword(s):  
Copy Number ◽  
Gene Evolution ◽  
Gene Copy Number ◽  
In Vitro Translation ◽  
Gene Copy ◽  
Release Factor ◽  
Bacterial Growth Rate ◽  
New Genes ◽  
Peptide Release

Abstract When new genes evolve through modification of existing genes, there are often tradeoffs between the new and original functions, making gene duplication and amplification necessary to buffer deleterious effects on the original function. We have used experimental evolution of a bacterial strain lacking peptide release factor 1 (RF1) in order to study how peptide release factor 2 (RF2) evolves to compensate the loss of RF1. As expected, amplification of the RF2-encoding gene prfB to high copy number was a rapid initial response, followed by the appearance of mutations in RF2 and other components of the translation machinery. Characterization of the evolved RF2 variants by their effects on bacterial growth rate, reporter gene expression, and in vitro translation termination reveals a complex picture of reduced discrimination between the cognate and near-cognate stop codons and highlights a functional tradeoff that we term “collateral toxicity.” We suggest that this type of tradeoff may be a more serious obstacle in new gene evolution than the more commonly discussed evolutionary tradeoffs between “old” and “new” functions of a gene, as it cannot be overcome by gene copy number changes. Further, we suggest a model for how RF2 autoregulation responds to alterations in the demand not only for RF2 activity but also for RF1 activity.

scholarly journals Cloning of the PYR3 gene of Ustilago maydis and its use in DNA transformation.

1988 ◽  
Vol 8 (12) ◽  
pp. 5417-5424 ◽  
Author(s):  
G R Banks ◽  
S Y Taylor
Keyword(s):  
Dna Sequences ◽  
Gene Copy Number ◽  
Mutant Gene ◽  
Ustilago Maydis ◽  
Gene Copy ◽  
Wild Type ◽  
Gene Encoding ◽  
E Coli ◽  
Multiple Transcripts ◽  
Different Types

The Ustilago maydis PYR3 gene encoding dihydroorotase activity was cloned by direct complementation of Escherichia coli pyrC mutations. PYR3 transformants of E. coli pyrC mutants expressed homologous transcripts of a variety of sizes and regained dihydroorotase activity. PYR3 also complemented Saccharomyces cerevisiae ura4 mutations, and again multiple transcripts were expressed in transformants, and enzyme activity was regained. A 1.25-kilobase poly(rA)+ PYR3 transcript was detected in U. maydis itself. Linear DNA carrying the PYR3 gene transformed a U. maydis pyr3-1 pyrimidine auxotroph to prototrophy. Hybridization analysis revealed that three different types of transformants could be generated, depending on the structure of the transforming DNA used. The first type involved exchange of chromosomal mutant gene sequences with the cloned wild-type plasmid sequences. A second type had integrated linear transforming DNA at the chromosomal PYR3 locus, probably via a single crossover event. The third type had integrated transforming DNA sequences at multiple sites in the U. maydis genome. In the last two types, tandemly reiterated copies of the transforming DNA were found to have been integrated. All three types had lost the sensitivity of the parental pyr3-1 mutant to UV irradiation. They had also regained dihydroorotase activity, although its level did not correlate with the PYR3 gene copy number.

Cloning of the PYR3 gene of Ustilago maydis and its use in DNA transformation

1988 ◽  
Vol 8 (12) ◽  
pp. 5417-5424
Author(s):  
G R Banks ◽  
S Y Taylor
Keyword(s):  
Dna Sequences ◽  
Gene Copy Number ◽  
Mutant Gene ◽  
Ustilago Maydis ◽  
Gene Copy ◽  
Wild Type ◽  
Gene Encoding ◽  
E Coli ◽  
Multiple Transcripts ◽  
Different Types

The Ustilago maydis PYR3 gene encoding dihydroorotase activity was cloned by direct complementation of Escherichia coli pyrC mutations. PYR3 transformants of E. coli pyrC mutants expressed homologous transcripts of a variety of sizes and regained dihydroorotase activity. PYR3 also complemented Saccharomyces cerevisiae ura4 mutations, and again multiple transcripts were expressed in transformants, and enzyme activity was regained. A 1.25-kilobase poly(rA)+ PYR3 transcript was detected in U. maydis itself. Linear DNA carrying the PYR3 gene transformed a U. maydis pyr3-1 pyrimidine auxotroph to prototrophy. Hybridization analysis revealed that three different types of transformants could be generated, depending on the structure of the transforming DNA used. The first type involved exchange of chromosomal mutant gene sequences with the cloned wild-type plasmid sequences. A second type had integrated linear transforming DNA at the chromosomal PYR3 locus, probably via a single crossover event. The third type had integrated transforming DNA sequences at multiple sites in the U. maydis genome. In the last two types, tandemly reiterated copies of the transforming DNA were found to have been integrated. All three types had lost the sensitivity of the parental pyr3-1 mutant to UV irradiation. They had also regained dihydroorotase activity, although its level did not correlate with the PYR3 gene copy number.

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