Global mRNA Stability Is Not Associated with Levels of Gene Expression in Drosophila melanogaster But Shows a Negative Correlation with Codon Bias

2005 ◽  
Vol 61 (3) ◽  
pp. 306-314 ◽  
Author(s):  
Hans K. Stenøien ◽  
Wolfgang Stephan
2020 ◽  
Vol 12 (12) ◽  
pp. 2391-2402
Author(s):  
Aleksei Belyi ◽  
Eliza Argyridou ◽  
John Parsch

Abstract Sex chromosomes often differ from autosomes with respect to their gene expression and regulation. In Drosophila melanogaster, X-linked genes are dosage compensated by having their expression upregulated in the male soma, a process mediated by the X-chromosome-specific binding of the dosage compensation complex (DCC). Previous studies of X-linked gene expression found a negative correlation between a gene’s male-to-female expression ratio and its distance to the nearest DCC binding site in somatic tissues, including head and brain, which suggests that dosage compensation influences sex-biased gene expression. A limitation of the previous studies, however, was that they focused on endogenous X-linked genes and, thus, could not disentangle the effects of chromosomal position from those of gene-specific regulation. To overcome this limitation, we examined the expression of an exogenous reporter gene inserted at many locations spanning the X chromosome. We observed a negative correlation between the male-to-female expression ratio of the reporter gene and its distance to the nearest DCC binding site in somatic tissues, but not in gonads. A reporter gene’s location relative to a DCC binding site had greater influence on its expression than the local regulatory elements of neighboring endogenous genes, suggesting that intra-chromosomal variation in the strength of dosage compensation is a major determinant of sex-biased gene expression. Average levels of sex-biased expression did not differ between head and brain, but there was greater positional effect variation in the brain, which may explain the observed excess of endogenous sex-biased genes located on the X chromosome in this tissue.


Genetics ◽  
2002 ◽  
Vol 160 (2) ◽  
pp. 595-608 ◽  
Author(s):  
Jody Hey ◽  
Richard M Kliman

AbstractIn Drosophila, as in many organisms, natural selection leads to high levels of codon bias in genes that are highly expressed. Thus codon bias is an indicator of the intensity of one kind of selection that is experienced by genes and can be used to assess the impact of other genomic factors on natural selection. Among 13,000 genes in the Drosophila genome, codon bias has a slight positive, and strongly significant, association with recombination—as expected if recombination allows natural selection to act more efficiently when multiple linked sites segregate functional variation. The same reasoning leads to the expectation that the efficiency of selection, and thus average codon bias, should decline with gene density. However, this prediction is not confirmed. Levels of codon bias and gene expression are highest for those genes in an intermediate range of gene density, a pattern that may be the result of a tradeoff between the advantages for gene expression of close gene spacing and disadvantages arising from regulatory conflicts among tightly packed genes. These factors appear to overlay the more subtle effect of linkage among selected sites that gives rise to the association between recombination rate and codon bias.


Genetics ◽  
2003 ◽  
Vol 165 (2) ◽  
pp. 613-621 ◽  
Author(s):  
Douglas R Dorer ◽  
Jamie A Rudnick ◽  
Etsuko N Moriyama ◽  
Alan C Christensen

Abstract Within the unique Triplo-lethal region (Tpl) of the Drosophila melanogaster genome we have found a cluster of 20 genes encoding a novel family of proteins. This family is also present in the Anopheles gambiae genome and displays remarkable synteny and sequence conservation with the Drosophila cluster. The family is also present in the sequenced genome of D. pseudoobscura, and homologs have been found in Aedes aegypti mosquitoes and in four other insect orders, but it is not present in the sequenced genome of any noninsect species. Phylogenetic analysis suggests that the cluster evolved prior to the divergence of Drosophila and Anopheles (250 MYA) and has been highly conserved since. The ratio of synonymous to nonsynonymous substitutions and the high codon bias suggest that there has been selection on this family both for expression level and function. We hypothesize that this gene family is Tpl, name it the Osiris family, and consider possible functions. We also predict that this family of proteins, due to the unique dosage sensitivity and the lack of homologs in noninsect species, would be a good target for genetic engineering or novel insecticides.


2004 ◽  
Vol 287 (4) ◽  
pp. L764-L773 ◽  
Author(s):  
Loretta Sparkman ◽  
Vijayakumar Boggaram

Interleukin (IL)-8, a C-X-C chemokine, is a potent chemoattractant and an activator for neutrophils, T cells, and other immune cells. The airway and respiratory epithelia play important roles in the initiation and modulation of inflammatory responses via production of cytokines and surfactant. The association between elevated levels of nitric oxide (NO) and IL-8 in acute lung injury associated with sepsis, acute respiratory distress syndrome, respiratory syncytial virus infection in infants, and other inflammatory diseases suggested that NO may play important roles in the control of IL-8 gene expression in the lung. We investigated the role of NO in the control of IL-8 gene expression in H441 lung epithelial cells. We found that a variety of NO donors significantly induced IL-8 mRNA levels, and the increase in IL-8 mRNA was associated with an increase in IL-8 protein. NO induction of IL-8 mRNA was due to increases in IL-8 gene transcription and mRNA stability. NO induction of IL-8 mRNA levels was not inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and KT-5823, inhibitors of soluble guanylate cyclase and protein kinase G, respectively, and 8-bromo-cGMP did not increase IL-8 mRNA levels. This indicated that NO induces IL-8 mRNA levels independently of changes in the intracellular cGMP levels. NO induction of IL-8 mRNA was significantly reduced by inhibitors of extracellular regulated kinase and protein kinase C. IL-8 induction by NO was also reduced by hydroxyl radical scavengers such as dimethyl sulfoxide and dimethylthiourea, indicating the involvement of hydroxyl radicals in the induction process. NO induction of IL-8 gene expression could be a significant contributing factor in the initiation and induction of inflammatory response in the respiratory epithelium.


2013 ◽  
Vol 304 (3) ◽  
pp. R177-R188 ◽  
Author(s):  
Wendi S. Neckameyer ◽  
Kathryn J. Argue

Numerous studies have detailed the extensive conservation of developmental signaling pathways between the model system, Drosophila melanogaster, and mammalian models, but researchers have also profited from the unique and highly tractable genetic tools available in this system to address critical questions in physiology. In this review, we have described contributions that Drosophila researchers have made to mathematical dynamics of pattern formation, cardiac pathologies, the way in which pain circuits are integrated to elicit responses from sensation, as well as the ways in which gene expression can modulate diverse behaviors and shed light on human cognitive disorders. The broad and diverse array of contributions from Drosophila underscore its translational relevance to modeling human disease.


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