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The FEBS Journal Nov 2005The platelet-derived growth factor (PDGF) family was for more than 25 years assumed to consist of only PDGF-A and -B. The discovery of the novel family members PDGF-C... (Review)
Review
The platelet-derived growth factor (PDGF) family was for more than 25 years assumed to consist of only PDGF-A and -B. The discovery of the novel family members PDGF-C and PDGF-D triggered a search for novel activities and complementary fine tuning between the members of this family of growth factors. Since the expansion of the PDGF family, more than 60 publications on the novel PDGF-C and PDGF-D have been presented, highlighting similarities and differences to the classical PDGFs. In this paper we review the published data on the PDGF family covering structural (gene and protein) similarities and differences among all four family members, with special focus on PDGF-C and PDGF-D expression and functions. Little information on the protein structures of PDGF-C and -D is currently available, but the PDGF-C protein may be structurally more similar to VEGF-A than to PDGF-B. PDGF-C contributes to normal development of the heart, ear, central nervous system (CNS), and kidney, while PDGF-D is active in the development of the kidney, eye and brain. In adults, PDGF-C is active in the kidney and the central nervous system. PDGF-D also plays a role in the lung and in periodontal mineralization. PDGF-C is expressed in Ewing family sarcoma and PDGF-D is linked to lung, prostate and ovarian cancers. Both PDGF-C and -D play a role in progressive renal disease, glioblastoma/medulloblastoma and fibrosis in several organs.
Topics: Alternative Splicing; Amino Acid Motifs; Amino Acid Sequence; Animals; Codon, Initiator; Codon, Terminator; Cysteine; Dimerization; Disulfides; Exons; Humans; Introns; Lymphokines; Mice; Mice, Knockout; Models, Molecular; Molecular Sequence Data; Platelet-Derived Growth Factor; Promoter Regions, Genetic; Protein Binding; Protein Processing, Post-Translational; Protein Sorting Signals; Protein Structure, Secondary; Protein Structure, Tertiary; Receptors, Platelet-Derived Growth Factor; Sequence Homology, Amino Acid
PubMed: 16279938
DOI: 10.1111/j.1742-4658.2005.04989.x -
Philosophical Transactions of the Royal... Feb 2000A genome is not a simple collection of genes. We propose here that it can be viewed as being organized as a 'celluloculus' similar to the homunculus of preformists, but... (Review)
Review
A genome is not a simple collection of genes. We propose here that it can be viewed as being organized as a 'celluloculus' similar to the homunculus of preformists, but pertaining to the category of programmes (or algorithms) rather than to that of architectures or structures: a significant correlation exists between the distribution of genes along the chromosome and the physical architecture of the cell. We review here data supporting this observation, stressing physical constraints operating on the cell's architecture and dynamics, and their consequences in terms of gene and genome structure. If such a correlation exists, it derives from some selection pressure: simple and general physical principles acting at the level of the cell structure are discussed. As a first case in point we see the piling up of planar modules as a stable, entropy-driven, architectural principle that could be at the root of the coupling between the architecture of the cell and the location of genes at specific places in the chromosome. We propose that the specific organization of certain genes whose products have a general tendency to form easily planar modules is a general motor for architectural organization in the bacterial cell. A second mechanism, operating at the transcription level, is described that could account for the efficient building up of complex structures. As an organizing principle we suggest that exploration by biological polymers of the vast space of possible conformation states is constrained by anchoring points. In particular, we suggest that transcription does not always allow the 5'-end of the transcript to go free and explore the many conformations available, but that, in many cases, it remains linked to the transcribing RNA polymerase complex in such a way that loops of RNA, rather than threads with a free end, explore the surrounding medium. In bacteria, extension of the loops throughout the cytoplasm would therefore be mediated by the de novo synthesis of ribosomes in growing cells. Termination of transcription and mRNA turnover would accordingly be expected to be controlled by sequence features at both the 3'- and 5'-ends of the molecule. These concepts are discussed taking into account in vitro analysis of genome sequences and experimental data about cell compartmentalization, mRNA folding and turnover, as well as known structural features of protein and membrane complexes.
Topics: Chromosome Mapping; Chromosomes, Bacterial; Codon; Genome, Bacterial; Prokaryotic Cells; Protein Biosynthesis
PubMed: 10724454
DOI: 10.1098/rstb.2000.0557 -
PloS One 2022Despite its high and direct impact on nearly all biological processes, the underlying structure of gene-gene interaction networks is investigated so far according to...
Despite its high and direct impact on nearly all biological processes, the underlying structure of gene-gene interaction networks is investigated so far according to pair connections. To address this, we explore the gene interaction networks of the yeast Saccharomyces cerevisiae beyond pairwise interaction using the structural balance theory (SBT). Specifically, we ask whether essential and nonessential gene interaction networks are structurally balanced. We study triadic interactions in the weighted signed undirected gene networks and observe that balanced and unbalanced triads are over and underrepresented in both networks, thus beautifully in line with the strong notion of balance. Moreover, we note that the energy distribution of triads is significantly different in both essential and nonessential networks compared to the shuffled networks. Yet, this difference is greater in the essential network regarding the frequency as well as the energy of triads. Additionally, results demonstrate that triads in the essential gene network are more interconnected through sharing common links, while in the nonessential network they tend to be isolated. Last but not least, we investigate the contribution of all-length signed walks and its impact on the degree of balance. Our findings reveal that interestingly when considering longer cycles, not only, both essential and nonessential gene networks are more balanced compared to their corresponding shuffled networks, but also, the nonessential gene network is more balanced compared to the essential network.
Topics: Gene Regulatory Networks; Genes, Essential; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 35353818
DOI: 10.1371/journal.pone.0258596 -
RNA Biology Sep 2016Pre-mRNA splicing is a key post-transcriptional regulation process in which introns are excised and exons are ligated together. A novel class of structured intron was... (Review)
Review
Pre-mRNA splicing is a key post-transcriptional regulation process in which introns are excised and exons are ligated together. A novel class of structured intron was recently discovered in fish. Simple expansions of complementary AC and GT dimers at opposite boundaries of an intron were found to form a bridging structure, thereby enforcing correct splice site pairing across the intron. In some fish introns, the RNA structures are strong enough to bypass the need of regulatory protein factors for splicing. Here, we discuss the prevalence and potential functions of highly structured introns. In humans, structured introns usually arise through the co-occurrence of C and G-rich repeats at intron boundaries. We explore the potentially instructive example of the HLA receptor genes. In HLA pre-mRNA, structured introns flank the exons that encode the highly polymorphic β sheet cleft, making the processing of the transcript robust to variants that disrupt splicing factor binding. While selective forces that have shaped HLA receptor are fairly atypical, numerous other highly polymorphic genes that encode receptors contain structured introns. Finally, we discuss how the elevated mutation rate associated with the simple repeats that often compose structured intron can make structured introns themselves rapidly evolving elements.
Topics: Animals; Biological Evolution; Exons; Humans; Introns; Nucleic Acid Conformation; Polymorphism, Single Nucleotide; RNA; RNA Precursors; RNA Splicing; RNA, Messenger; Splicing Factor U2AF; Structure-Activity Relationship
PubMed: 27454491
DOI: 10.1080/15476286.2016.1208893 -
Molecular Biology and Evolution Aug 2018The Universal Gene Set of Life (UGSL) is common to genomes of all extant organisms. The UGSL is small, consisting of <100 genes, and is dominated by genes encoding the...
The Universal Gene Set of Life (UGSL) is common to genomes of all extant organisms. The UGSL is small, consisting of <100 genes, and is dominated by genes encoding the translation system. Here we extend the search for biological universality to three dimensions. We characterize and quantitate the universality of structure of macromolecules that are common to all of life. We determine that around 90% of prokaryotic ribosomal RNA (rRNA) forms a common core, which is the structural and functional foundation of rRNAs of all cytoplasmic ribosomes. We have established a database, which we call the Sparse and Efficient Representation of the Extant Biology (the SEREB database). This database contains complete and cross-validated rRNA sequences of species chosen, as far as possible, to sparsely and efficiently sample all known phyla. Atomic-resolution structures of ribosomes provide data for structural comparison and validation of sequence-based models. We developed a similarity statistic called pairing adjusted sequence entropy, which characterizes paired nucleotides by their adherence to covariation and unpaired nucleotides by conventional conservation of identity. For canonically paired nucleotides the unit of structure is the nucleotide pair. For unpaired nucleotides, the unit of structure is the nucleotide. By quantitatively defining the common core of rRNA, we systematize the conservation and divergence of the translational system across the tree of life, and can begin to understand the unique evolutionary pressures that cause its universality. We explore the relationship between ribosomal size and diversity, geological time, and organismal complexity.
Topics: Animals; Escherichia coli; Evolution, Molecular; Genes, Essential; Genetic Techniques; Humans; Protein Biosynthesis; RNA, Ribosomal
PubMed: 29788252
DOI: 10.1093/molbev/msy101 -
International Journal of Molecular... Oct 2023The copper transporter (/) gene family plays a critical part in maintaining the balance of the metal, and many diverse species depend on to move copper (Cu) across the... (Review)
Review
The copper transporter (/) gene family plays a critical part in maintaining the balance of the metal, and many diverse species depend on to move copper (Cu) across the cell membrane. In , , , , , , and a genome-wide study of the COPT protein family was performed. To understand the major roles of the gene family in (), a genome-wide study identified four genes in the genome for the first time. The domain and 3D structural variation, phylogenetic tree, chromosomal distributions, gene structure, motif analysis, subcellular localization, cis-regulatory elements, synteny and duplication analysis, and expression profiles in leaves and Cu were all investigated in this research. Structural and sequence investigations show that most have three transmembrane domains (TMDs). According to phylogenetic research, these might be divided into two subgroups, just like . gene segmental duplications and positive selection pressure were discovered by universal analysis. According to gene structure and motif analysis, most genes showed consistent exon-intron and motif organization within the same group. In addition, we found five hormones and four stress- and seven light-responsive cis-elements in the promoters. The expression studies revealed that all four genes changed their expression levels in response to copper (CuCl) treatments. In summary, our study offers a thorough overview of the gene family's expression pattern and functional diversity, making it easier to characterize each gene's function in the future.
Topics: Copper; Copper Transport Proteins; Gene Expression Profiling; Gene Expression Regulation, Plant; Genes, Plant; Genome-Wide Association Study; Multigene Family; Phylogeny; Plant Proteins; Rhizophoraceae
PubMed: 37958561
DOI: 10.3390/ijms242115579 -
BMC Evolutionary Biology May 2009The 12-oxo-phytodienoic acid reductases (OPRs) are enzymes that catalyze the reduction of double-bonds in alpha, beta-unsaturated aldehydes or ketones and are part of...
BACKGROUND
The 12-oxo-phytodienoic acid reductases (OPRs) are enzymes that catalyze the reduction of double-bonds in alpha, beta-unsaturated aldehydes or ketones and are part of the octadecanoid pathway that converts linolenic acid to jasmonic acid. In plants, OPRs belong to the old yellow enzyme family and form multigene families. Although discoveries about this family in Arabidopsis and other species have been reported in some studies, the evolution and function of multiple OPRs in plants are not clearly understood.
RESULTS
A comparative genomic analysis was performed to investigate the phylogenetic relationship, structural evolution and functional divergence among OPR paralogues in plants. In total, 74 OPR genes were identified from 11 species representing the 6 major green plant lineages: green algae, mosses, lycophytes, gymnosperms, monocots and dicots. Phylogenetic analysis showed that seven well-conserved subfamilies exist in plants. All OPR genes from green algae were clustered into a single subfamily, while those from land plants fell into six other subfamilies, suggesting that the events leading to the expansion of the OPR family occurred in land plants. Further analysis revealed that lineage-specific expansion, especially by tandem duplication, contributed to the current OPR subfamilies in land plants after divergence from aquatic plants. Interestingly, exon/intron structure analysis showed that the gene structures of OPR paralogues exhibits diversity in intron number and length, while the intron positions and phase were highly conserved across different lineage species. These observations together with the phylogenetic tree revealed that successive single intron loss, as well as indels within introns, occurred during the process of structural evolution of OPR paralogues. Functional divergence analysis revealed that altered functional constraints have occurred at specific amino acid positions after diversification of the paralogues. Most notably, significant functional divergence was also found in all pairs, except for the II/IV, II/V and V/VI pairs. Strikingly, analysis of the site-specific profiles established by posterior probability revealed that the positive-selection sites and/or critical amino acid residues for functional divergence are mainly distributed in alpha-helices and substrate binding loop (SBL), indicating the functional importance of these regions for this protein family.
CONCLUSION
This study highlights the molecular evolution of the OPR gene family in all plant lineages and indicates critical amino acid residues likely relevant for the distinct functional properties of the paralogues. Further experimental verification of these findings may provide valuable information on the OPRs' biochemical and physiological functions.
Topics: Amino Acid Sequence; Comparative Genomic Hybridization; DNA, Plant; Evolution, Molecular; Genes, Plant; INDEL Mutation; Introns; Molecular Sequence Data; Multigene Family; Oxidoreductases Acting on CH-CH Group Donors; Phylogeny; Plants; Selection, Genetic; Sequence Alignment
PubMed: 19416520
DOI: 10.1186/1471-2148-9-90 -
PloS One 2019The deluge of sequence information in the recent times provide us with an excellent opportunity to compare organisms on a large genomic scale. In this study we have...
Comparative in silico analysis of ftsZ gene from different bacteria reveals the preference for core set of codons in coding sequence structuring and secondary structural elements determination.
The deluge of sequence information in the recent times provide us with an excellent opportunity to compare organisms on a large genomic scale. In this study we have tried to decipher the variation in the gene organization and structuring of a vital bacterial gene called ftsZ which codes for an integral component of the bacterial cell division, the FtsZ protein. FtsZ is homologous to tubulin protein and has been found to be ubiquitous in eubacteria. FtsZ is showing increasing promise as a target for antibacterial drug discovery. Our study of ftsZ protein from 143 different bacterial species spanning a wider range of morphological and physiological type demonstrates that the ftsZ gene of about ninety three percent of the organisms show relatively biased codon usage profile and significant GC deviation from their genomic GC content. Comparative codon usage analysis of ftsZ and a core housekeeping gene rpoB demonstrated that codon usage pattern of ftsZ CDS is shaped by natural selection to a large extent and mimics that of a housekeeping gene. We have also detected a tendency among the different organisms to utilize a core set of codons in structuring the ftsZ coding sequence. We observed that the compositional frequency of the amino acid serine in the FtsZ protein appears to be a indicator of the bacterial lifestyle. Our meticulous analysis of the ftsZ gene linked with the corresponding FtsZ protein show that there is a bias towards the use of specific synonymous codons particularly in the helix and strand regions of the multi-domain FtsZ protein. Overall our findings suggest that in an indispensable and vital protein such as FtsZ, there is an inherent tendency to maintain form for optimized performance in spite of the extrinsic variability in coding features.
Topics: Amino Acid Sequence; Bacteria; Bacterial Proteins; Base Composition; Codon; Codon Usage; Computer Simulation; Cytoskeletal Proteins; Genes, Bacterial; Genomics; Open Reading Frames; Selection, Genetic; Tubulin
PubMed: 31841523
DOI: 10.1371/journal.pone.0219231 -
Journal of Biochemistry May 1996To better understand the regulation of ryudocan (syndecan-4) expression, we have determined the structural organization of the human ryudocan gene. The human ryudocan...
To better understand the regulation of ryudocan (syndecan-4) expression, we have determined the structural organization of the human ryudocan gene. The human ryudocan gene extends approximately 24 kilobases and is divided into five exons, which appear to be conserved in syndecan family members. Exon I encodes the signal peptide; exons II-IV, the extracellular domain; and exon V, the transmembrane and cytoplasmic domains, which are highly homologous among syndecan family members. Primer extension analysis showed that human ryudocan gene had a single transcription initiation site, located 3 bases upstream from the described cDNA [Kojima et al. (1993) BBRC 190, 814-822]. The 5'-flanking sequences of human ryudocan gene contain a TATA-like sequence as well as a variety of other potential binding sites for transcription factors, including Sp1, Ap-2, NF-kB, E-alpha H box, H4TF-2, and LBP-1, and were capable of functioning as a promoter. The determination of the human ryudocan gene structure will allow elucidation of constitutive, cell-specific, tissue-specific, and developmentally regulated expression.
Topics: Animals; Base Sequence; Binding Sites; COS Cells; Exons; Genes; Genes, Reporter; Humans; Introns; Luciferases; Membrane Glycoproteins; Molecular Sequence Data; Promoter Regions, Genetic; Proteoglycans; Restriction Mapping; Syndecan-4; Transcription Factors
PubMed: 8797100
DOI: 10.1093/oxfordjournals.jbchem.a021338 -
DNA Research : An International Journal... Aug 2023The prediction of gene structure within the genome sequence is the starting point of genome analysis, and its accuracy has a significant impact on the quality of...
The prediction of gene structure within the genome sequence is the starting point of genome analysis, and its accuracy has a significant impact on the quality of subsequent analyses. Gene structure prediction is roughly divided into RNA-Seq-based methods, ab initio-based methods, homology-based methods, and the integration of individual prediction methods. Integrated methods are mainstream in recent genome projects because they improve prediction accuracy by combining or taking the best individual prediction findings; however, adequate prediction accuracy for eukaryotic species has not yet been achieved. Therefore, we developed an integrated tool, GINGER, that solves various issues related to gene structure prediction in higher eukaryotes. By handling artefacts in alignments of RNA and protein sequences, reconstructing gene structures via dynamic programming with appropriately weighted and scored exon/intron/intergenic regions, and applying different prediction processes and filtering criteria to multi-exon and single-exon genes, we achieved a significant improvement in accuracy compared to the existing integration methods. The feature of GINGER is its high prediction accuracy at the gene and exon levels, which is pronounced for species with more complex gene architectures. GINGER is implemented using Nextflow, which allows for the efficient and effective use of computing resources.
Topics: Zingiber officinale; Eukaryota; Genome; Exons; Introns; Algorithms; Software
PubMed: 37478310
DOI: 10.1093/dnares/dsad017