Redundant and cryptic enhancer activities of the Drosophila yellow gene

2018 ◽  
Author(s):  
Gizem Kalay ◽  
Jennifer Lachowiec ◽  
Ulises Rosas ◽  
Mackenzie R. Dome ◽  
Patricia Wittkopp

Abstractcis-regulatory sequences known as enhancers play a key role in regulating gene expression. Evolutionary changes in these DNA sequences contribute to phenotypic evolution. The Drosophila yellow gene, which is required for pigmentation, has emerged as a model system for understanding how cis-regulatory sequences evolve, providing some of the most detailed insights available into how activities of orthologous enhancers have diverged between species. Here, we examine the evolution of yellow cis-regulatory sequences on a broader scale by comparing the distribution and function of yellow enhancer activities throughout the 5’ intergenic and intronic sequences of Drosophila melanogaster, Drosophila pseudoobscura, and Drosophila willistoni. We find that cis-regulatory sequences driving expression in a particular tissue are not as modular as previously described, but rather have many redundant and cryptic enhancer activities distributed throughout the regions surveyed. Interestingly, cryptic enhancer activities of sequences from one species often drove patterns of expression observed in other species, suggesting that the frequent evolutionary changes in yellow expression observed among Drosophila species may be facilitated by gaining and losing repression of pre-existing cis-regulatory sequences.

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Rubén Mollá-Albaladejo ◽  
Juan A. Sánchez-Alcañiz

Among individuals, behavioral differences result from the well-known interplay of nature and nurture. Minute differences in the genetic code can lead to differential gene expression and function, dramatically affecting developmental processes and adult behavior. Environmental factors, epigenetic modifications, and gene expression and function are responsible for generating stochastic behaviors. In the last decade, the advent of high-throughput sequencing has facilitated studying the genetic basis of behavior and individuality. We can now study the genomes of multiple individuals and infer which genetic variations might be responsible for the observed behavior. In addition, the development of high-throughput behavioral paradigms, where multiple isogenic animals can be analyzed in various environmental conditions, has again facilitated the study of the influence of genetic and environmental variations in animal personality. Mainly, Drosophila melanogaster has been the focus of a great effort to understand how inter-individual behavioral differences emerge. The possibility of using large numbers of animals, isogenic populations, and the possibility of modifying neuronal function has made it an ideal model to search for the origins of individuality. In the present review, we will focus on the recent findings that try to shed light on the emergence of individuality with a particular interest in D. melanogaster.


1990 ◽  
Vol 259 (4) ◽  
pp. L185-L197
Author(s):  
B. R. Stripp ◽  
J. A. Whitsett ◽  
D. L. Lattier

Gene transcription is regulated by the formation of protein-DNA complexes that influence the rate of specific initiation of transcription by RNA polymerase. Recent experimental advances allowing the identification of cis regulatory sequences that specify the binding of trans acting protein factors have made significant contributions to our understanding of the mechanistic complexities of transcriptional regulation. These methodologies have prompted the use of similar strategies to elucidate transcriptional control mechanisms involved in the tissue specific and developmental regulation of pulmonary surfactant protein gene expression. The purpose of this review is to describe various methodologies by which molecular biologists identify and subsequently assay regions of nucleic acids presumed to be integral in gene regulation at the level of transcription. It is well established that genes encoding surfactant proteins are subject to regulation by hormones, cytokines, and a variety of biologically active reagents. Perhaps future studies utilizing molecular tools outlined in this review will be valuable in identification of DNA sequences and protein factors required for the regulation of lung surfactant genes.


1989 ◽  
Vol 9 (3) ◽  
pp. 1173-1182
Author(s):  
K Lowenhaupt ◽  
A Rich ◽  
M L Pardue

Long stretches of (dC-dA)n.(dT-dG)n, abbreviated CA/TG, have a distinctive distribution on Drosophila chromosomes (M.L. Pardue, K. Lowenhaupt, A. Rich, and A. Nordheim, EMBO J. 6:1781-1789, 1987). The distribution of CA/TG suggests a correlation with the overall transcriptional activity of chromosomal regions and with the ability to undergo meiotic recombination. These correlations are conserved among Drosophila species and may indicate one or more chromosomal functions. To test the generality of these findings, we analyzed the distribution of the rest of the six possible mono- and dinucleotide repeats (A/T, C/G, AT/AT, CA/TG, CT/AG, and CG/CG). All but CG/CG were present at significant levels in the genomes of the six Drosophila species studied; however, A/T levels were an order of magnitude lower than those of the other sequences. Data base analyses suggested that the same sequences are present in other eucaryotes. Like CA/TG, both CT/AG and C/G showed increased levels on dosage-compensating chromosomes; however, the individual sites clearly differed for each sequence. In contrast, A/T and AT/AT, although present in Drosophila DNA, could not be detected in situ in polytene chromosomes. We also used in situ hybridization to analyze the neo-Y chromosome of Drosophila miranda, an ancestral autosome that has become attached to the Y chromosome and is now partially heterochromatic. The neo-Y has acquired repeated DNA sequences; we found that the added sequences are as devoid of mono- and dinucleotide repeats as other heterochromatin. The distribution and function of these sequences are likely to result from both their repetitious nature and base contents.


2015 ◽  
Vol 2015 ◽  
pp. 1-19 ◽  
Author(s):  
Kimberly A. Carlson ◽  
Kylee Gardner ◽  
Anjeza Pashaj ◽  
Darby J. Carlson ◽  
Fang Yu ◽  
...  

Aging is a complex process characterized by a steady decline in an organism’s ability to perform life-sustaining tasks. In the present study, two cages of approximately 12,000 mated Drosophila melanogaster females were used as a source of RNA from individuals sampled frequently as a function of age. A linear model for microarray data method was used for the microarray analysis to adjust for the box effect; it identified 1,581 candidate aging genes. Cluster analyses using a self-organizing map algorithm on the 1,581 significant genes identified gene expression patterns across different ages. Genes involved in immune system function and regulation, chorion assembly and function, and metabolism were all significantly differentially expressed as a function of age. The temporal pattern of data indicated that gene expression related to aging is affected relatively early in life span. In addition, the temporal variance in gene expression in immune function genes was compared to a random set of genes. There was an increase in the variance of gene expression within each cohort, which was not observed in the set of random genes. This observation is compatible with the hypothesis that D. melanogaster immune function genes lose control of gene expression as flies age.


1995 ◽  
Vol 73 (S1) ◽  
pp. 876-884 ◽  
Author(s):  
William E. Hintz ◽  
Inge Kalsner ◽  
Ewa Plawinski ◽  
Zimin Guo ◽  
Peter A. Lagosky

A variety of gene expression systems have been developed that utilize the promoter and transcriptional regulatory sequences derived from carbon-catabolite repressed genes for the expression of heterologous genes. The alcA expression system of Aspergillus nidulans utilizes the promoter and regulatory sequences derived from the alcohol dehydrogenase I (alcA) gene. Expression of the alcA gene is repressed by a DNA-binding protein (CreA) in the presence of glucose and induced by ethanol under glucose-depleted conditions. One problem encountered during the expression of therapeutic proteins in A. nidulans is the coexpression of secreted proteases at the time of maximal secretion of heterologous product. To avoid the proteases we created an alcA promoter variant that is no longer sensitive to glucose repression hence could drive expression at earlier time points during the fermentation. The use of this promoter variant in the expression of recombinant interleukin-6 is discussed. A second problem encountered during the expression of high-quality human therapeutic proteins in Aspergillus is aberrant glycosylation. Lower eukaryotic systems, such as Aspergillus, tend to add highly branched mannosidic chains to heterologous secreted protein products. N-Glycans can be important for both the structure and function of specific glycoproteins, hence efforts are being made to in vivo alter the type and complexity of N-glycans substituted by A. nidulans. Key words: Aspergillus, gene expression, alcohol dehydrogenase, glycosylation.


2015 ◽  
Vol 112 (24) ◽  
pp. 7524-7529 ◽  
Author(s):  
Shigeyuki Koshikawa ◽  
Matt W. Giorgianni ◽  
Kathy Vaccaro ◽  
Victoria A. Kassner ◽  
John H. Yoder ◽  
...  

Changes in gene expression during animal development are largely responsible for the evolution of morphological diversity. However, the genetic and molecular mechanisms responsible for the origins of new gene-expression domains have been difficult to elucidate. Here, we sought to identify molecular events underlying the origins of three novel features of wingless (wg) gene expression that are associated with distinct pigmentation patterns in Drosophila guttifera. We compared the activity of cis-regulatory sequences (enhancers) across the wg locus in D. guttifera and Drosophila melanogaster and found strong functional conservation among the enhancers that control similar patterns of wg expression in larval imaginal discs that are essential for appendage development. For pupal tissues, however, we found three novel wg enhancer activities in D. guttifera associated with novel domains of wg expression, including two enhancers located surprisingly far away in an intron of the distant Wnt10 gene. Detailed analysis of one enhancer (the vein-tip enhancer) revealed that it overlapped with a region controlling wg expression in wing crossveins (crossvein enhancer) in D. guttifera and other species. Our results indicate that one novel domain of wg expression in D. guttifera wings evolved by co-opting pre-existing regulatory sequences governing gene activity in the developing wing. We suggest that the modification of existing enhancers is a common path to the evolution of new gene-expression domains and enhancers.


Genetics ◽  
1994 ◽  
Vol 137 (4) ◽  
pp. 1057-1070 ◽  
Author(s):  
J A Birchler ◽  
U Bhadra ◽  
L Rabinow ◽  
R Linsk ◽  
A T Nguyen-Huynh

Abstract A locus is described in Drosophila melanogaster that modifies the expression of the white eye color gene. This trans-acting modifier reduces the expression of the white gene in the eye, but elevates the expression in other adult tissues. Because of the eye phenotype in which the expression of white is lessened but not eliminated, the newly described locus is called the Weakener of white (Wow). Northern analysis reveals that Wow can exert an inverse or direct modifying effect depending upon the developmental stage. Two related genes, brown and scarlet, that are coordinately expressed with white, are also affected by Wow. In addition, Wow modulates the steady state RNA level of the retrotransposon, copia. When tested with a white promoter-Alcohol dehydrogenase reporter. Wow confers the modifying effect to the reporter, suggesting a requirement of the white regulatory sequences for mediating the response. In addition to being a dosage sensitive regulator of white, brown, scarlet and copia, Wow acts as a suppressor of position effect variegation. There are many dosage sensitive suppressors of position effect variegation and many dosage-sensitive modifiers of gene expression. The Wow mutations provide evidence for an overlap between the two types of modifiers.


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