The evolution of hemocyanin genes in Tectipleura: a multitude of conserved introns in highly diverse gastropods

Abstract Background Hemocyanin is the oxygen transporter of most molluscs. Since the oxygen affinity of hemocyanin is strongly temperature-dependent, this essential protein needs to be well-adapted to the environment. In Tectipleura, a very diverse group of gastropods with > 27,000 species living in all kinds of habitats, several hemocyanin genes have already been analyzed. Multiple independent duplications of this gene have been identified and may represent potential adaptations to different environments and lifestyles. The aim of this study is to further explore the evolution of these genes by analyzing their exon–intron architectures. Results We have reconstructed the gene architectures of ten hemocyanin genes from four Tectipleura species: Aplysia californica, Lymnaea stagnalis, Cornu aspersum and Helix pomatia. Their hemocyanin genes each contain 53 introns, significantly more than in the hemocyanin genes of Cephalopoda (9–11), Vetigastropoda (15) and Caenogastropoda (28–33). The gene structures of Tectipleura hemocyanins are identical in terms of intron number and location, with the exception of one out of two hemocyanin genes of L. stagnalis that comprises one additional intron. We found that gene structures that differ between molluscan lineages most probably evolved more recently through independent intron gains. Conclusions The strict conservation of the large number of introns in Tectipleura hemocyanin genes over 200 million years suggests the influence of a selective pressure on this gene structure. While we could not identify conserved sequence motifs within these introns, it may be simply the great number of introns that offers increased possibilities of gene regulation relative to hemocyanin genes with less introns and thus may have facilitated habitat shifts and speciation events. This hypothesis is supported by the relatively high number of introns within the hemocyanin genes of Pomacea canaliculata that has evolved independently of the Tectipleura. Pomacea canaliculata belongs to the Caenogastropoda, the sister group of Heterobranchia (that encompass Tectipleura) which is also very diverse and comprises species living in different habitats. Our findings provide a hint to some of the molecular mechanisms that may have supported the spectacular radiation of one of Metazoa’s most species rich groups.

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lncRNAs in development and differentiation: from sequence motifs to functional characterization

Development ◽

10.1242/dev.182741 ◽

2021 ◽

Vol 148 (1) ◽

pp. dev182741

Author(s):

Florian Constanty ◽

Alena Shkumatava

Keyword(s):

Molecular Mechanisms ◽

Functional Characterization ◽

Sequence Motifs ◽

Cellular Functions ◽

Rna Motifs ◽

Rna Sequences ◽

Conserved Sequence ◽

Interaction Partners ◽

Sequence Elements ◽

Development And Differentiation

ABSTRACTThe number of long noncoding RNAs (lncRNAs) with characterized developmental and cellular functions continues to increase, but our understanding of the molecular mechanisms underlying lncRNA functions, and how they are dictated by RNA sequences, remains limited. Relatively short, conserved sequence motifs embedded in lncRNA transcripts are often important determinants of lncRNA localization, stability and interactions. Identifying such RNA motifs remains challenging due to the substantial length of lncRNA transcripts and the rapid evolutionary turnover of lncRNA sequences. Nevertheless, the recent discovery of specific RNA elements, together with their experimental interrogation, has enabled the first step in classifying heterogeneous lncRNAs into sub-groups with similar molecular mechanisms and functions. In this Review, we focus on lncRNAs with roles in development, cell differentiation and normal physiology in vertebrates, and we discuss the sequence elements defining their functions. We also summarize progress on the discovery of regulatory RNA sequence elements, as well as their molecular functions and interaction partners.

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Amino Acid Sequence Motifs Essential for P0-Mediated Suppression of RNA Silencing in an Isolate of Potato leafroll virus from Inner Mongolia

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi-08-13-0231-r ◽

2014 ◽

Vol 27 (6) ◽

pp. 515-527 ◽

Cited By ~ 26

Author(s):

Tao Zhuo ◽

Yuan-Yuan Li ◽

Hai-Ying Xiang ◽

Zhan-Yu Wu ◽

Xian-Bin Wang ◽

...

Keyword(s):

Rna Silencing ◽

Molecular Mechanisms ◽

Alternative Pathway ◽

Potato Leafroll Virus ◽

Sequence Motifs ◽

Suppressor Activity ◽

Conserved Sequence ◽

Complex Protein ◽

Proteasome Pathway ◽

Leafroll Virus

Polerovirus P0 suppressors of host gene silencing contain a consensus F-box-like motif with Leu/Pro (L/P) requirements for suppressor activity. The Inner Mongolian Potato leafroll virus (PLRV) P0 protein (P0PL-IM) has an unusual F-box-like motif that contains a Trp/Gly (W/G) sequence and an additional GW/WG-like motif (G139/W140/G141) that is lacking in other P0 proteins. We used Agrobacterium infiltration-mediated RNA silencing assays to establish that P0PL-IM has a strong suppressor activity. Mutagenesis experiments demonstrated that the P0PL-IM F-box-like motif encompasses amino acids 76-LPRHLHYECLEWGLLCG THP-95, and that the suppressor activity is abolished by L76A, W87A, or G88A substitution. The suppressor activity is also weakened substantially by mutations within the G139/W140/G141 region and is eliminated by a mutation (F220R) in a C-terminal conserved sequence of P0PL-IM. As has been observed with other P0 proteins, P0PL-IM suppression is correlated with reduced accumulation of the host AGO1-silencing complex protein. However, P0PL-IM fails to bind SKP1, which functions in a proteasome pathway that may be involved in AGO1 degradation. These results suggest that P0PL-IM may suppress RNA silencing by using an alternative pathway to target AGO1 for degradation. Our results help improve our understanding of the molecular mechanisms involved in PLRV infection.

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DNABERT: pre-trained Bidirectional Encoder Representations from Transformers model for DNA-language in genome

Bioinformatics ◽

10.1093/bioinformatics/btab083 ◽

2021 ◽

Author(s):

Yanrong Ji ◽

Zhihan Zhou ◽

Han Liu ◽

Ramana V Davuluri

Keyword(s):

Dna Sequences ◽

Regulatory Elements ◽

Ease Of Use ◽

Fine Tuning ◽

Supplementary Information ◽

Sequence Motifs ◽

Semantic Relationship ◽

Accurate Identification ◽

Conserved Sequence ◽

Genome Wide

Abstract Motivation Deciphering the language of non-coding DNA is one of the fundamental problems in genome research. Gene regulatory code is highly complex due to the existence of polysemy and distant semantic relationship, which previous informatics methods often fail to capture especially in data-scarce scenarios. Results To address this challenge, we developed a novel pre-trained bidirectional encoder representation, named DNABERT, to capture global and transferrable understanding of genomic DNA sequences based on up and downstream nucleotide contexts. We compared DNABERT to the most widely used programs for genome-wide regulatory elements prediction and demonstrate its ease of use, accuracy and efficiency. We show that the single pre-trained transformers model can simultaneously achieve state-of-the-art performance on prediction of promoters, splice sites and transcription factor binding sites, after easy fine-tuning using small task-specific labeled data. Further, DNABERT enables direct visualization of nucleotide-level importance and semantic relationship within input sequences for better interpretability and accurate identification of conserved sequence motifs and functional genetic variant candidates. Finally, we demonstrate that pre-trained DNABERT with human genome can even be readily applied to other organisms with exceptional performance. We anticipate that the pre-trained DNABERT model can be fined tuned to many other sequence analyses tasks. Availability and implementation The source code, pretrained and finetuned model for DNABERT are available at GitHub (https://github.com/jerryji1993/DNABERT). Supplementary information Supplementary data are available at Bioinformatics online.

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Molecular Pathways Involved in the Development of Congenital Erythrocytosis

Genes ◽

10.3390/genes12081150 ◽

2021 ◽

Vol 12 (8) ◽

pp. 1150

Author(s):

Jana Tomc ◽

Nataša Debeljak

Keyword(s):

Signal Transduction ◽

Iron Homeostasis ◽

Molecular Mechanisms ◽

Oxygen Affinity ◽

Molecular Pathways ◽

Disease Development ◽

Post Translational Modifications ◽

Hemoglobin Oxygen Affinity ◽

Insight Into ◽

Idiopathic Erythrocytosis

Patients with idiopathic erythrocytosis are directed to targeted genetic testing including nine genes involved in oxygen sensing pathway in kidneys, erythropoietin signal transduction in pre-erythrocytes and hemoglobin-oxygen affinity regulation in mature erythrocytes. However, in more than 60% of cases the genetic cause remains undiagnosed, suggesting that other genes and mechanisms must be involved in the disease development. This review aims to explore additional molecular mechanisms in recognized erythrocytosis pathways and propose new pathways associated with this rare hematological disorder. For this purpose, a comprehensive review of the literature was performed and different in silico tools were used. We identified genes involved in several mechanisms and molecular pathways, including mRNA transcriptional regulation, post-translational modifications, membrane transport, regulation of signal transduction, glucose metabolism and iron homeostasis, which have the potential to influence the main erythrocytosis-associated pathways. We provide valuable theoretical information for deeper insight into possible mechanisms of disease development. This information can be also helpful to improve the current diagnostic solutions for patients with idiopathic erythrocytosis.

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Olfactory expression of trace amine-associated receptors requires cooperative cis-acting enhancers

Nature Communications ◽

10.1038/s41467-021-23824-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Ami Shah ◽

Madison Ratkowski ◽

Alessandro Rosa ◽

Paul Feinstein ◽

Thomas Bozza

Keyword(s):

Gene Expression ◽

Large Family ◽

Sequence Motifs ◽

Specific Expression ◽

Cis Acting ◽

Conserved Sequence ◽

Trace Amine ◽

Sequence Elements ◽

Cell Type Specific Expression ◽

Cell Type Specific

AbstractOlfactory sensory neurons express a large family of odorant receptors (ORs) and a small family of trace amine-associated receptors (TAARs). While both families are subject to so-called singular expression (expression of one allele of one gene), the mechanisms underlying TAAR gene choice remain obscure. Here, we report the identification of two conserved sequence elements in the mouse TAAR cluster (T-elements) that are required for TAAR gene expression. We observed that cell-type-specific expression of a TAAR-derived transgene required either T-element. Moreover, deleting either element reduced or abolished expression of a subset of TAAR genes, while deleting both elements abolished olfactory expression of all TAARs in cis with the mutation. The T-elements exhibit several features of known OR enhancers but also contain highly conserved, unique sequence motifs. Our data demonstrate that TAAR gene expression requires two cooperative cis-acting enhancers and suggest that ORs and TAARs share similar mechanisms of singular expression.

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Antimutator mutations in the alpha subunit of Escherichia coli DNA polymerase III: identification of the responsible mutations and alignment with other DNA polymerases.

Genetics ◽

10.1093/genetics/134.4.1039 ◽

1993 ◽

Vol 134 (4) ◽

pp. 1039-1044 ◽

Cited By ~ 2

Author(s):

I J Fijalkowska ◽

R M Schaaper

Keyword(s):

Escherichia Coli ◽

Amino Acid ◽

Dna Polymerase ◽

Dna Polymerases ◽

Alpha Subunit ◽

Sequence Motifs ◽

Dna Polymerase Iii ◽

Conserved Sequence ◽

Polymerase Iii ◽

Dna Replication Errors

Abstract The dnaE gene of Escherichia coli encodes the DNA polymerase (alpha subunit) of the main replicative enzyme, DNA polymerase III holoenzyme. We have previously identified this gene as the site of a series of seven antimutator mutations that specifically decrease the level of DNA replication errors. Here we report the nucleotide sequence changes in each of the different antimutator dnaE alleles. For each a single, but different, amino acid substitution was found among the 1,160 amino acids of the protein. The observed substitutions are generally nonconservative. All affected residues are located in the central one-third of the protein. Some insight into the function of the regions of polymerase III containing the affected residues was obtained by amino acid alignment with other DNA polymerases. We followed the principles developed in 1990 by M. Delarue et al. who have identified in DNA polymerases from a large number of prokaryotic and eukaryotic sources three highly conserved sequence motifs, which are suggested to contain components of the polymerase active site. We succeeded in finding these three conserved motifs in polymerase III as well. However, none of the amino acid substitutions responsible for the antimutator phenotype occurred at these sites. This and other observations suggest that the effect of these mutations may be exerted indirectly through effects on polymerase conformation and/or DNA/polymerase interactions.

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The first crystal structure of the peptidase domain of the U32 peptidase family

Acta Crystallographica Section D Biological Crystallography ◽

10.1107/s1399004715019549 ◽

2015 ◽

Vol 71 (12) ◽

pp. 2505-2512 ◽

Cited By ~ 4

Author(s):

Magdalena Schacherl ◽

Angelika A. M. Montada ◽

Elena Brunstein ◽

Ulrich Baumann

Keyword(s):

Crystal Structure ◽

Catalytic Mechanism ◽

Quaternary Structure ◽

Catalytic Domain ◽

Three Dimensional ◽

Zinc Ion ◽

Crystal Structure Analysis ◽

Dimensional Structure ◽

Sequence Motifs ◽

Conserved Sequence

The U32 family is a collection of over 2500 annotated peptidases in the MEROPS database with unknown catalytic mechanism. They mainly occur in bacteria and archaea, but a few representatives have also been identified in eukarya. Many of the U32 members have been linked to pathogenicity, such as proteins fromHelicobacterandSalmonella. The first crystal structure analysis of a U32 catalytic domain fromMethanopyrus kandleri(genemk0906) reveals a modified (βα)8TIM-barrel fold with some unique features. The connecting segment between strands β7 and β8 is extended and helix α7 is located on top of the C-terminal end of the barrel body. The protein exhibits a dimeric quaternary structure in which a zinc ion is symmetrically bound by histidine and cysteine side chains from both monomers. These residues reside in conserved sequence motifs. No typical proteolytic motifs are discernible in the three-dimensional structure, and biochemical assays failed to demonstrate proteolytic activity. A tunnel in which an acetate ion is bound is located in the C-terminal part of the β-barrel. Two hydrophobic grooves lead to a tunnel at the C-terminal end of the barrel in which an acetate ion is bound. One of the grooves binds to aStrep-Tag II of another dimer in the crystal lattice. Thus, these grooves may be binding sites for hydrophobic peptides or other ligands.

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Molecular and Cytological Analyses of Large Tracks of Centromeric DNA Reveal the Structure and Evolutionary Dynamics of Maize Centromeres

Genetics ◽

10.1093/genetics/163.2.759 ◽

2003 ◽

Vol 163 (2) ◽

pp. 759-770 ◽

Cited By ~ 5

Author(s):

Kiyotaka Nagaki ◽

Junqi Song ◽

Robert M Stupar ◽

Alexander S Parokonny ◽

Qiaoping Yuan ◽

...

Keyword(s):

Evolutionary Dynamics ◽

Artificial Chromosome ◽

Grass Species ◽

Sequence Motifs ◽

Long Terminal Repeats ◽

Satellite Repeat ◽

Sequence Comparisons ◽

Centromeric Dna ◽

Conserved Sequence ◽

Satellite Sequences

Abstract We sequenced two maize bacterial artificial chromosome (BAC) clones anchored by the centromere-specific satellite repeat CentC. The two BACs, consisting of ∼200 kb of cytologically defined centromeric DNA, are composed exclusively of satellite sequences and retrotransposons that can be classified as centromere specific or noncentromere specific on the basis of their distribution in the maize genome. Sequence analysis suggests that the original maize sequences were composed of CentC arrays that were expanded by retrotransposon invasions. Seven centromere-specific retrotransposons of maize (CRM) were found in BAC 16H10. The CRM elements inserted randomly into either CentC monomers or other retrotransposons. Sequence comparisons of the long terminal repeats (LTRs) of individual CRM elements indicated that these elements transposed within the last 1.22 million years. We observed that all of the previously reported centromere-specific retrotransposons in rice and barley, which belong to the same family as the CRM elements, also recently transposed with the oldest element having transposed ∼3.8 million years ago. Highly conserved sequence motifs were found in the LTRs of the centromere-specific retrotransposons in the grass species, suggesting that the LTRs may be important for the centromere specificity of this retrotransposon family.

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Conserved sequence motifs among bacterial, eukaryotic, and archaeal phosphatases that define a new phosphohydrolase superfamily

Protein Science ◽

10.1002/pro.5560070722 ◽

1998 ◽

Vol 7 (7) ◽

pp. 1647-1652 ◽

Cited By ~ 96

Author(s):

Maria Cristina Thaller ◽

Serena Schippa ◽

Gian Maria Rossolini

Keyword(s):

Sequence Motifs ◽

Conserved Sequence ◽

Conserved Sequence Motifs

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The murine Ki-67 cell proliferation antigen accumulates in the nucleolar and heterochromatic regions of interphase cells and at the periphery of the mitotic chromosomes in a process essential for cell cycle progression

Journal of Cell Science ◽

10.1242/jcs.109.1.143 ◽

1996 ◽

Vol 109 (1) ◽

pp. 143-153 ◽

Cited By ~ 14

Author(s):

M. Starborg ◽

K. Gell ◽

E. Brundell ◽

C. Hoog

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Tandem Repeats ◽

Sequence Motifs ◽

Mitotic Chromosomes ◽

Proliferating Cells ◽

Ki 67 ◽

Cycle Progression ◽

Conserved Sequence ◽

Interphase Cells

We have isolated the murine homologue of the human Ki-67 antigen. The Ki-67 antigen is used as a marker to assess the proliferative capacity of tumour cells; however, its cellular function is not known. The murine Ki-67 cDNA sequence (TSG126) was found to contain 13 tandem repeats, making up more than half of the total protein size. A comparison of this repetitive sequence block to its human counterpart, which contains 16 consecutive repeat units, revealed several conserved sequence motifs, including one motif frequently observed in proteins interacting with DNA. An antiserum developed against the product of the TSG126 cDNA clone identified a protein with an apparent molecular mass of 360 kDa, mainly expressed in proliferating cells. The TSG126 protein begins to accumulate during the late G1 stage of the cell cycle and is first seen as numerous small granules evenly distributed throughout the nucleus. During the S and the G2 phases, larger foci that overlap with the nucleoli and the heterochromatic regions are formed. At the onset of mitosis the TSG126 protein undergoes a dramatic redistribution process and becomes associated with the surface of the condensed chromosomes. The relative absence of the TSG126 protein from G1 interphase cells strongly argues against a model where the association of the TSG126 protein with mitotic chromosomes merely reflects a mechanism for the symmetrical distribution of nucleolar proteins between daughter cells. Instead, the intracellular distribution of the TSG126 protein during the cell cycle suggests that it could have a chromatin-associated function in both interphase and mitotic cells. Microinjection of anti-TSG126 antibodies into proliferating Swiss-3T3 fibroblasts was found to delay cell cycle progression, indicating that the TSG126 protein has an essential nuclear function.

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