scuteexpression inCalliphora vicinareveals an ancestral pattern of longitudinal stripes on the thorax of higher Diptera

Development ◽  
2002 ◽  
Vol 129 (3) ◽  
pp. 563-572 ◽  
Author(s):  
Daniela Pistillo ◽  
Nick Skaer ◽  
Pat Simpson
Keyword(s):  
Expression Pattern ◽  
Regulatory Elements ◽  
Calliphora Vicina ◽  
Transcriptional Activators ◽  
Gene Complex ◽  
Secondary Loss ◽  
Evolutionary Changes ◽  
Sensory Bristles ◽  
And Function ◽  
Bristle Patterns

In Drosophila the stereotyped arrangement of sensory bristles on the notum is determined by the tightly regulated control of transcription of the achaete-scute (ac-sc) genes which are expressed in small proneural clusters of cells at the sites of each future bristle. Expression relies on a series of discrete cis-regulatory elements present in the ac-sc gene complex that are the target of the transcriptional activators pannier (pnr) and the genes of the iroquois complex. Stereotyped bristle patterns are common among species of acalyptrate Schizophora such as Drosophila, and are thought to have derived from an ancestral pattern of four longitudinal rows extending the length of the scutum, through secondary loss of bristles. To investigate evolutionary changes in bristle patterns and ac-sc regulation by pnr, we have isolated homologues of these genes from Calliphora vicina, a species of calyptrate Schizophora separated from Drosophila by at least 100 million years. Calliphora vicina displays a pattern of four rows of bristles on the scutum resembling the postulated ancestral one. We find that sc in Calliphora is expressed in two longitudinal stripes on the medial scutum that prefigure the development of the rows of acrostichal and dorsocentral bristles. This result suggests that a stripe-like expression pattern of sc may be an ancestral feature and may have preceded the evolution of proneural clusters. The implications for the evolution of the cis-regulatory elements responsible for sc expression in the proneural clusters of Drosophila, and function of Pnr are discussed.

scholarly journals Recapitulating Evolutionary Divergence in a Single Cis-Regulatory Element Is Sufficient to Cause Expression Changes of the Lens Gene Tdrd7

2020 ◽  
Author(s):  
Juliana G Roscito ◽  
Kaushikaram Subramanian ◽  
Ronald Naumann ◽  
Mihail Sarov ◽  
Anna Shevchenko ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Mrna Level ◽  
Regulatory Elements ◽  
Evolutionary Divergence ◽  
Phenotypic Differences ◽  
Evolutionary Changes ◽  
Mole Rat ◽  
Regulatory Mutations ◽  
Subterranean Mammals ◽  
And Function

Abstract Mutations in cis-regulatory elements play important roles for phenotypic changes during evolution. Eye degeneration in the blind mole rat (BMR; Nannospalax galili) and other subterranean mammals is significantly associated with widespread divergence of eye regulatory elements, but the effect of these regulatory mutations on eye development and function has not been explored. Here, we investigate the effect of mutations observed in the BMR sequence of a conserved noncoding element upstream of Tdrd7, a pleiotropic gene required for lens development and spermatogenesis. We first show that this conserved element is a transcriptional repressor in lens cells and that the BMR sequence partially lost repressor activity. Next, we recapitulated evolutionary changes in this element by precisely replacing the endogenous regulatory element in a mouse line by the orthologous BMR sequence with CRISPR–Cas9. Strikingly, this repressor replacement caused a more than 2-fold upregulation of Tdrd7 in the developing lens; however, increased mRNA level does not result in a corresponding increase in TDRD7 protein nor an obvious lens phenotype, possibly explained by buffering at the posttranscriptional level. Our results are consistent with eye degeneration in subterranean mammals having a polygenic basis where many small-effect mutations in different eye-regulatory elements collectively contribute to phenotypic differences.

scholarly journals Repression precedes the stepwise evolution of a highly specific gene expression pattern

2020 ◽  
Author(s):  
Jian Pu ◽  
Zinan Wang ◽  
Haosu Cong ◽  
Jacqueline S.R. Chin ◽  
Jessa Justen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Pattern ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Regulatory Elements ◽  
Fatty Acyl ◽  
Specific Gene ◽  
Spatial Expression ◽  
Origin And Evolution ◽  
And Function

AbstractWell-controlled gene expression is critical for the proper development and function of many traits. Highly-specific temporal and spatial expression patterns are often due to the overlapping activities of activator and repressor sequences that form cis-regulatory elements called enhancers. While many studies have shown that evolutionary changes in enhancers can result in novel traits, few studies illuminate how enhancers originate, how activator and repressor sequences interact during enhancer evolution, and the order in which they evolve. Here, we traced the evolutionary origin of a recently evolved enhancer that drives the expression of the fatty acyl-CoA elongase, bond, specifically in the semicircular wall epithelium (swe) of the Drosophila male ejaculatory bulb (EB). We show that this enhancer consists of two activator regions that drive bond expression in the entire EB and a repressor region that restricts expression specifically to the EB swe. Interestingly, the repressor region preceded the evolution of the two activator regions. The evolution of the first activator region, consisting of two putative Abdominal-B sites, did not drive expression in the EB due to the action of the repressor region. Expression of bond in the EB swe requires the evolution of the second activator region, which does not drive expression on its own, but synergizes with the first activator region and the repressor region to produce a highly-specific spatial expression pattern. Our results show that the origin and evolution of a novel enhancer require multiple steps and the evolution of repressor sequences can precede the evolution of activator sequences.

scholarly journals Recapitulating evolutionary divergence in a single cis-regulatory element is sufficient to cause expression changes of the lens gene Tdrd7

2020 ◽  
Author(s):  
Juliana G. Roscito ◽  
Kaushikaram Subramanian ◽  
Ronald Naumann ◽  
Mihail Sarov ◽  
Anna Shevchenko ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Mrna Level ◽  
Regulatory Elements ◽  
Evolutionary Divergence ◽  
Phenotypic Differences ◽  
Evolutionary Changes ◽  
Mole Rat ◽  
Regulatory Mutations ◽  
Subterranean Mammals ◽  
And Function

ABSTRACTMutations in cis-regulatory elements play important roles for phenotypic changes during evolution. Eye degeneration in the blind mole rat (BMR) and other subterranean mammals is significantly associated with widespread divergence of eye regulatory elements, but the effect of these regulatory mutations on eye development and function has not been explored. Here, we investigate the effect of mutations observed in the BMR sequence of a conserved non-coding element upstream of Tdrd7, a pleiotropic gene required for lens development and spermatogenesis. We first show that this conserved element is a transcriptional repressor in lens cells and that the BMR sequence partially lost repressor activity. Next, we recapitulated the evolutionary changes by precisely replacing the endogenous regulatory element in a mouse line by the orthologous BMR sequence with CRISPR-Cas9. Strikingly, this repressor element has a large effect, causing a more than two-fold up-regulation of Tdrd7 in developing lens. Interestingly, the increased mRNA level does not result in a corresponding increase in TDRD7 protein nor an obvious lens phenotype, likely explained by buffering at the posttranscriptional level. Our results are consistent with eye degeneration in subterranean mammals having a polygenic basis where many small-effect mutations in different eye-regulatory elements collectively contribute to phenotypic differences.

scholarly journals Evolutionary changes in transcription factor coding sequence quantitatively alter sensory organ development and function

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Simon Weinberger ◽  
Matthew P Topping ◽  
Jiekun Yan ◽  
Annelies Claeys ◽  
Natalie De Geest ◽  
...  
Keyword(s):  
Morphological Evolution ◽  
Regulatory Elements ◽  
Sensory Organ ◽  
Sequence Evolution ◽  
Mrna Levels ◽  
Proneural Genes ◽  
Coding Sequence ◽  
Evolutionary Changes ◽  
And Function

Animals are characterized by a set of highly conserved developmental regulators. Changes in the cis-regulatory elements of these regulators are thought to constitute the major driver of morphological evolution. However, the role of coding sequence evolution remains unresolved. To address this question, we used the Atonal family of proneural transcription factors as a model. Drosophila atonal coding sequence was endogenously replaced with that of atonal homologues (ATHs) at key phylogenetic positions, non-ATH proneural genes, and the closest homologue to ancestral proneural genes. ATHs and the ancestral-like coding sequences rescued sensory organ fate in atonal mutants, in contrast to non-ATHs. Surprisingly, different ATH factors displayed different levels of proneural activity as reflected by the number and functionality of sense organs. This proneural potency gradient correlated directly with ATH protein stability, including in response to Notch signaling, independently of mRNA levels or codon usage. This establishes a distinct and ancient function for ATHs and demonstrates that coding sequence evolution can underlie quantitative variation in sensory development and function.

scholarly journals The Drosophila engrailed and invected Genes: Partners in Regulation, Expression and Function

Genetics ◽  
1996 ◽  
Vol 142 (3) ◽  
pp. 893-906 ◽  
Author(s):  
Elizabeth Gustavson ◽  
Andrew S Goldsborough ◽  
Zehra Ali ◽  
Thomas B Kornberg
Keyword(s):  
Expression Pattern ◽  
Cultured Cells ◽  
Regulatory Region ◽  
Embryonic Lethality ◽  
Wild Type ◽  
Terminal Portion ◽  
Coding Sequence ◽  
Differential Effects ◽  
And Function ◽  
Redundant Functions

Abstract We isolated and characterized numerous engrailed and invected alleles. Among the deficiencies we isolated, a mutant lacking invected sequences was viable and phenotypically normal, a mutant lacking engrailed was an embryo lethal and had slight segmentation defects, and a mutant lacking both engrailed and invected was most severely affected. In seven engrailed alleles, mutations caused translation to terminate prematurely in the central or C-terminal portion of the coding sequence, resulting in embryonic lethality and segmentation defects. Both engrailed and invected expression declined prematurely in these mutant embryos. In wild-type embryos, engrailed and invected are juxtaposed and are expressed in essentially identical patterns. A breakpoint mutant that separates the mgrailed and invected transcription units parceled different aspects of the expression pattern to engrailed or invected. We also found that both genes cause similar defects when expressed ectopically and that the protein products of both genes act to repress transcription in cultured cells. We propose that the varied phenotypes of the engrailed alleles can be explained by the differential effects these mutants have on the combination of engrailed and invected activities, that engrailed and invected share a regulatory region, and that they encode redundant functions.

scholarly journals Cell-specific expression and individual function of prohormone convertase PC1/3 in Tribolium larval growth highlights major evolutionary changes between beetle and fly neuroendocrine systems

EvoDevo ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sonja Fritzsche ◽  
Vera S. Hunnekuhl
Keyword(s):  
Larval Growth ◽  
Neuroendocrine System ◽  
Small Subset ◽  
Specific Cell ◽  
Specific Expression ◽  
Individual Function ◽  
Evolutionary Changes ◽  
Cell Groups ◽  
Cell Type Specific Expression ◽  
And Function

Abstract Background The insect neuroendocrine system acts in the regulation of physiology, development and growth. Molecular evolution of this system hence has the potential to allow for major biological differences between insect groups. Two prohormone convertases, PC1/3 and PC2, are found in animals and both function in the processing of neuropeptide precursors in the vertebrate neurosecretory pathway. Whereas PC2-function is conserved between the fly Drosophila and vertebrates, ancestral PC1/3 was lost in the fly lineage and has not been functionally studied in any protostome. Results In order to understand its original functions and the changes accompanying the gene loss in the fly, we investigated PC1/3 and PC2 expression and function in the beetle Tribolium castaneum. We found that PC2 is broadly expressed in the nervous system, whereas surprisingly, PC1/3 expression is restricted to specific cell groups in the posterior brain and suboesophageal ganglion. Both proteases have parallel but non-redundant functions in adult beetles’ viability and fertility. Female infertility following RNAi is caused by a failure to deposit sufficient yolk to the developing oocytes. Larval RNAi against PC2 produced moulting defects where the larvae were not able to shed their old cuticle. This ecdysis phenotype was also observed in a small subset of PC1/3 knockdown larvae and was strongest in a double knockdown. Unexpectedly, most PC1/3-RNAi larvae showed strongly reduced growth, but went through larval moults despite minimal to zero weight gain. Conclusions The cell type-specific expression of PC1/3 and its essential requirement for larval growth highlight the important role of this gene within the insect neuroendocrine system. Genomic conservation in most insect groups suggests that it has a comparable individual function in other insects as well, which has been replaced by alternative mechanisms in flies.

scholarly journals The decapentaplegic core promoter region plays an integral role in the spatial control of transcription.

1995 ◽  
Vol 15 (7) ◽  
pp. 3960-3968 ◽  
Author(s):  
D H Schwyter ◽  
J D Huang ◽  
T Dubnicoff ◽  
A J Courey
Keyword(s):  
Expression Pattern ◽  
Phase Ii ◽  
Promoter Region ◽  
Core Promoter ◽  
Critical Role ◽  
Regulatory Elements ◽  
Drosophila Embryo ◽  
Phase Iii ◽  
Core Promoter Region ◽  
Flanking Region

The Drosophila melanogaster decapentaplegic (dpp) gene encodes a transforming growth factor beta-related cell signaling molecule that plays a critical role in dorsal/ventral pattern formation. The dpp expression pattern in the Drosophila embryo is dynamic, consisting of three phases. Phase I, in which dpp is expressed in a broad dorsal domain, depends on elements in the dpp second intron that interact with the Dorsal transcription factor to repress transcription ventrally. In contrast, phases II and III, in which dpp is expressed first in broad longitudinal stripes (phase II) and subsequently in narrow longitudinal stripes (phase III), depend on multiple independent elements in the dpp 5'-flanking region. Several aspects of the normal dpp expression pattern appear to depend on the unique properties of the dpp core promoter. For example, this core promoter (extending from -22 to +6) is able to direct a phase II expression pattern in the absence of additional upstream or downstream regulatory elements. In addition, a ventral-specific enhancer in the dpp 5'-flanking region that binds the Dorsal factor activates the heterologous hsp70 core promoter but not the dpp core promoter. Thus, the dpp core promoter region may contribute to spatially regulated transcription both by interacting directly with spatially restricted activators and by modifying the activity of proteins bound to enhancer elements.

Multiple regulatory elements direct the complex expression pattern of the Drosophila segmentation gene paired

1994 ◽  
Vol 48 (2) ◽  
pp. 119-128 ◽  
Author(s):  
Thomas Gutjahr ◽  
Carlos E. Vanario-Alonso ◽  
Leslie Pick ◽  
Markus Noll
Keyword(s):  
Expression Pattern ◽  
Regulatory Elements ◽  
Segmentation Gene ◽  
Complex Expression

Ecdysterone regulatory elements function as both transcriptional activators and repressors

1991 ◽  
Vol 11 (4) ◽  
pp. 1846-1853
Author(s):  
L Dobens ◽  
K Rudolph ◽  
E M Berger
Keyword(s):  
Regulatory Element ◽  
Regulatory Elements ◽  
Upstream Region ◽  
Transcriptional Activators ◽  
Reporter Plasmid ◽  
Bacterial Gene ◽  
Simplex Virus ◽  
Very High ◽  
Cat Gene ◽  
Cat Expression

A synthetic, 23-bp ecdysterone regulatory element (EcRE), derived from the upstream region of the Drosophila melanogaster hsp27 gene, was inserted adjacent to the herpes simplex virus thymidine kinase promoter fused to a bacterial gene for chloramphenicol acetyltransferase (CAT). Hybrid constructs were transfected into Drosophila S3 cells and assayed for ecdysterone-inducible CAT expression. In the absence of ecdysterone a tandem pair of EcREs repressed the high constitutive level of CAT activity found after transfection with the parent reporter plasmid alone. After hormone addition very high levels of CAT activity were observed. Insertion of the EcRE pair 3' of the CAT gene also led to high levels of ecdysterone-induced CAT expression, but the repression of high constitutive levels of CAT activity failed to occur. The EcRE-CAT construct was cotransfected with plasmids containing tandem 10-mers or 40-mers of the EcRE but lacking a reporter gene. These additional EcREs led to a reduced level of ecdysterone-induced CAT activity and to an elevation of basal CAT activity in the absence of hormone. The data suggest that the receptor binds to the EcRE in the absence of hormone, blocking basal transcription from a constitutive promoter. In the presence of ecdysterone, receptor-hormone binding to the EcRE leads to greatly enhanced transcription.

scholarly journals Extrachromosomal DNA: An Emerging Hallmark in Human Cancer

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Sihan Wu ◽  
Vineet Bafna ◽  
Howard Y. Chang ◽  
Paul S. Mischel
Keyword(s):  
Human Cancer ◽  
Regulatory Elements ◽  
Annual Review ◽  
Publication Date ◽  
Cancer Evolution ◽  
Form And Function ◽  
Current State ◽  
Human Genes ◽  
Cancer Tumor ◽  
And Function

Human genes are arranged on 23 pairs of chromosomes, but in cancer, tumor-promoting genes and regulatory elements can free themselves from chromosomes and relocate to circular, extrachromosomal pieces of DNA (ecDNA). ecDNA, because of its nonchromosomal inheritance, drives high-copy-number oncogene amplification and enables tumors to evolve their genomes rapidly. Furthermore, the circular ecDNA architecture fundamentally alters gene regulation and transcription, and the higher-order organization of ecDNA contributes to tumor pathogenesis. Consequently, patients whose cancers harbor ecDNA have significantly shorter survival. Although ecDNA was first observed more than 50 years ago, its critical importance has only recently come to light. In this review, we discuss the current state of understanding of how ecDNAs form and function as well as how they contribute to drug resistance and accelerated cancer evolution. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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