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At least 955 records · Page 53Linked to original sources
PubMed1997

Two two-gene macronuclear chromosomes of the hypotrichous ciliates Oxytricha fallax and O. trifallax generated by alternative processing of the 81 locus.

We describe the first know macronuclear chromosomes that carry more than one gene in hypotrichous ciliated protozoa. These 4.9- and 2.8-kbp chromosomes each consist almost exclusively of two protein-coding genes, which are conserved and transcribed. The two chromosomes share a common region that consists of a gene that is a member of the family of mitochondrial solute carrier genes (CR-MSC; [Williams and Herrick (1991): Nucleic Acids Res 19:4717-4724]. Each chromosome also carries another gene appended to its common region: The 4.9-kbp chromosome also carries a gene that encodes a protein that is rich in glutamine and charged amino acids and bears regions of heptad repeats characteristic of coiled-coils. Its function is unknown. The second gene of the 2.8 kbp chromosome is a mitochondrial solute carrier gene (LA-MSC); thus, the 2.8-kbp chromosomes consists of two mitochondrial solute carrier paralogs. Phylogenetic analysis indicates that the two genes were duplicated before ciliates diverged from the main eukaryotic lineage and were subsequently juxtaposed. The CR- and LA-MSC genes are each interrupted by three introns. The introns are not in homologous positions, suggesting that they may have originated from multiple group II intron transpositions. These chromosomes and their genes are encoded in the Oxytricha germline by the 81 locus. This locus is alternatively processed to generate a nested set of three macronuclear chromosomes, the 4.9- and 2.8-kbp chromosomes and a third (1.6 kbp) which consists almost exclusively of the shared common gene, CR-MSC. Such alternative processing is common in macronuclear development of O. fallax [Cartinhour and Herrick (1984): Mol Cell Biol 4:931-938]. Possible functions for alternative processing are considered; e.g., it may serve to physically link genes to allow co-regulation or co-replication by a common cis-acting sequence.

Animals↗
PubMed1998

Evolution of the "classical" cadherin family of cell adhesion molecules in vertebrates.

The cadherins are major mediators of calcium-dependent cell-cell adhesion and are also involved in cell signaling pathways during development. The classical cadherins, which are the definitive group of the cadherin superfamily, are transmembrane proteins that consist of an extracellular domain of five cadherin repeats, including an HAV tripeptide conserved in one binding surface within the first domain, and a highly conserved cytoplasmic domain that interacts with the actin cytoskeleton via the catenin proteins. These cadherins play major roles in vertebrate morphogenesis; they are expressed widely throughout development, antibodies to specific cadherins perturb a variety of developmental processes, and many gene knockouts are lethal at early stages of development. Phylogenetic analysis of the "classical" cadherins shows that in the vertebrates there are four paralog families. The rate of evolutionary change is radically different between the different paralogs, indicating that there are significantly different selection pressures on the functions of the various cadherins, both between the different paralogs in a single organism lineage and between different organism lineages within a single paralog family. There is also evidence for gene conversion between the E-cadherin and P-cadherin paralogs in Gallus gallus and possibly Xenopus laevis, but not between the same paralogs in the mammalian lineages. A scheme for the origin of the paralogs within the vertebrate lineage based on these analyses indicates that the presence of the four paralog families is a characteristic of vertebrates and that variation of cadherin structure and function is a significant factor in morphological evolution of vertebrates.

Animals↗
PubMed2006

Rhox homeobox gene cluster: recent duplication of three family members.

We recently reported the discovery of a homeobox gene cluster on the mouse X chromosome, Rhox, whose 12 members are selectively expressed in specific cell types in reproductive organs. Here we report the existence of 20 additional Rhox homeobox genes in this gene cluster. Most of the newly identified Rhox paralogs retain the same order and relative orientation as three of the originally described Rhox genes, suggesting that they arose from recent duplications of this trimer unit. Many of these new Rhox family members are expressed in the testis and placenta. Analysis of synonymous and nonsynonymous substitutions in their homeodomain region suggests that these new Rhox paralogs duplicated so recently that their encoded proteins have not yet acquired distinct DNA-binding specificities. The existence of these new Rhox genes provides an opportunity to examine the initial stages of gene cluster evolution.

Amino Acid Sequence↗
PubMed2005

Analysis of the reticulon gene family demonstrates the absence of the neurite growth inhibitor Nogo-A in fish.

Reticulons (RTNs) are a family of evolutionary conserved proteins with four RTN paralogs (RTN1, RTN2, RTN3, and RTN4) present in land vertebrates. While the exact functions of RTN1 to RTN3 are unknown, mammalian RTN4-A/Nogo-A was shown to inhibit the regeneration of severed axons in the mammalian central nervous system (CNS). This inhibitory function is exerted via two distinct regions, one within the Nogo-A-specific N-terminus and the other in the conserved reticulon homology domain (RHD). In contrast to mammals, fish are capable of CNS axon regeneration. We performed detailed analyses of the fish rtn gene family to determine whether this regeneration ability correlates with the absence of the neurite growth inhibitory protein Nogo-A. A total of 7 rtn genes were identified in zebrafish, 6 in pufferfish, and 30 in eight additional fish species. Phylogenetic and syntenic relationships indicate that the identified fish rtn genes are orthologs of mammalian RTN1, RTN2, RTN3, and RTN4 and that several paralogous fish genes (e.g., rtn4 and rtn6) resulted from genome duplication events early in actinopterygian evolution. Accordingly, sequences homologous to the conserved RTN4/Nogo RHD are present in two fish genes, rtn4 and rtn6. However, sequences comparable to the first approximately 1,000 amino acids of mammalian Nogo-A including a major neurite growth inhibitory region are absent in zebrafish. This result is in accordance with functional data showing that axon growth inhibitory molecules are less prominent in fish oligodendrocytes and CNS myelin compared to mammals.

Animals↗
PubMed2001

Identifying genes for male sex determination in humans.

The convergence of genetic and molecular technologies has led to the identification of a number of genes for male sex determination. The observation of chromosomal translocations, deletions, and duplications in sex reversed individuals was instrumental for the positional cloning of SRY, SOX9, WT1, and DAX1. Cloning by protein-DNA interaction was required for the identification of SF1. The observation of an extended phenotype for the alpha thalassemia-mental retardation syndrome assigned a role for XH2 in the testicular determining process. Over the next several years, new sex determining genes will be identified by linkage analysis in large families with multiple sex reversed members, comparative genomic hybridization of sex reversed individuals, and database searches for genes that encode interacting proteins or paralogs of other species. Given the apparent differences in the sex determining mechanisms of even closely related species, the roles of all of these genes will require confirmation by demonstrating expression in human gonadal ridge at the critical time, and that mutations result in sex reversal.

Chromosome Mapping↗
PubMed2005

The new vertebrate CYP1C family: cloning of new subfamily members and phylogenetic analysis.

Two novel CYP1 genes from teleost fish constituting a new subfamily have been cloned. These paralogous sequences are designated CYP1C1 and CYP1C2. Both genes were initially obtained from untreated scup Stenotomus chrysops tissues by RT-PCR and RACE. Scup CYP1C1 and CYP1C2 code for 524 and 525 amino acids, respectively, and share 80-81% identity at the nucleotide and amino acid levels. Orthologues of CYP1C1 and CYP1C2 were identified in genome databases for other fish species, and both CYP1B1 and CYP1C1 were cloned from zebrafish (Danio rerio). Phylogenetic analysis shows that CYP1Cs and CYP1Bs constitute a sister clade to the CYP1As. Analysis of sequence domains likely to have functional significance suggests that the two CYP1Cs in scup may have catalytic functions and/or substrate specificity that differ from each other and from those of mammalian CYP1Bs or CYP1As. RT-PCR results indicate that CYP1C1 and CYP1C2 are variously expressed in several scup organs.

Amino Acid Sequence↗
PubMed2006

Evolutionary dynamics of Waxy and the origin of hexaploid Spartina species (Poaceae).

We investigated the evolutionary dynamics of duplicated copies of the granule-bound starch synthase I gene (GBSSI or Waxy) within polyploid Spartina species. Molecular cloning, sequencing, and phylogenetic analyses revealed incongruences between the expected species phylogeny and the inferred gene trees. Some genes within species were more divergent than expected from ploidy level alone, suggesting the existence of paralogous sets of Waxy loci in Spartina. Phylogenetic analyses indicate that this paralogy originated from a duplication that occurred prior to the divergence of Spartina from other Chloridoideae. Gene tree topologies revealed three divergent homoeologous sequences in the hexaploid S. alterniflora that are consistent with the proposal of an allopolyploid origin of the hexaploid clade. Waxy sequences differ in insertion-deletion events in introns, which may be used to diagnose gene copies. Both paralogous and homoeologous coding regions appear to evolving under selective constraints.

Base Sequence↗
PubMed2004

Functional differentiation in the mammalian metallothionein gene family: metal binding features of mouse MT4 and comparison with its paralog MT1.

This paper reports on the characterization of the metal binding abilities of mammalian MT4 and their comparison with those of the well known MT1. Heterologous Escherichia coli expression in cultures supplemented with zinc, cadmium, or copper was achieved for MT4 and for its separate alphaMT4 and betaMT4 domains as well as for MT1 and its alphaMT1 domain in cadmium-enriched medium. The in vivo conformed metal complexes and the in vitro substituted zinc/cadmium and zinc/copper MT4 aggregates were characterized. Biosynthesis of MT4 and betaMT4 in Cd(II)-supplemented medium revealed that these peptides failed to form the same homometallic species as MT1, thus appearing less effective for cadmium coordination. Conversely, the entire MT4 and both of its domains showed better Cu(I) binding properties than MT1, affording Cu(10)-MT4, Cu(5)-alphaMT4 and Cu(7)-betaMT4, stoichiometries that make the domain dependence toward Cu(I) clear. Overall results allow consideration of MT4 as a novel copper-thionein, made up of two copper-thionein domains, the first of this class reported in mammals, and by extension in vertebrates. Furthermore, the in silico protein sequence analyses corroborated the copper-thionein nature of the MT4 peptides. As a consequence, there is the suggestion of a possible physiological role played by MT4 related with copper requirements in epithelial differentiating tissues, where MT4 is expressed.

Amino Acid Sequence↗
PubMed2004

Many ribosomal protein genes are cancer genes in zebrafish.

We have generated several hundred lines of zebrafish (Danio rerio), each heterozygous for a recessive embryonic lethal mutation. Since many tumor suppressor genes are recessive lethals, we screened our colony for lines that display early mortality and/or gross evidence of tumors. We identified 12 lines with elevated cancer incidence. Fish from these lines develop malignant peripheral nerve sheath tumors, and in some cases also other tumor types, with moderate to very high frequencies. Surprisingly, 11 of the 12 lines were each heterozygous for a mutation in a different ribosomal protein (RP) gene, while one line was heterozygous for a mutation in a zebrafish paralog of the human and mouse tumor suppressor gene, neurofibromatosis type 2. Our findings suggest that many RP genes may act as haploinsufficient tumor suppressors in fish. Many RP genes might also be cancer genes in humans, where their role in tumorigenesis could easily have escaped detection up to now.

Animals↗
PubMed2002

The western red cedar (Thuja plicata) 8-8' DIRIGENT family displays diverse expression patterns and conserved monolignol coupling specificity.

The isolation and characterization of a multigene family of the first class of dirigent proteins (namely that mainly involved in 8-8' coupling leading to (+)-pinoresinol in this case) is reported, this comprising of nine western red cedar (Thuja plicata) DIRIGENT genes (DIR1-9) of 72-99.5% identity to each other. Their corresponding cDNA clones had coding regions for 180-183 amino acids with each having a predicted molecular mass of ca. 20 kDa including the signal peptide. Real time-PCR established that the DIRIGENT isovariants were differentially expressed during growth and development of T. plicata (P < 0.05). The phylogenetic relationships and the rates and patterns of nucleotide substitution suggest that the DIRIGENT gene may have evolved via paralogous expansion at an early stage of vascular plant diversification. Thereafter, western red cedar paralogues have maintained an high homogeneity presumably via a concerted evolutionary mode. This, in turn, is assumed to be the driving force for the differential formation of 8-8'-linked pinoresinol derived (poly)lignans in the needles, stems, bark and branches, as well as for massive accumulation of 8-8'-linked plicatic acid-derived (poly)lignans in heartwood.

Amino Acid Sequence↗
PubMedDate not supplied

Origin and evolution of the Amyrel gene in the alpha-amylase multigene family of Diptera.

Alpha-amylase genes often form multigene families in living organisms. In Diptera, a remote paralog, Amyrel, had been discovered in Drosophila, where this gene is currently used as a population and phylogenetic marker. The putative encoded protein has about 40% divergence with the classical amylases. We have searched the presence of the paralog in other families of Diptera to track its origin and understand its evolution. Amyrel was detected in a number of families of Muscomorpha (Brachycera-Cyclorrapha), suggesting an origin much older than previously thought. It has not been found elsewhere to date, and it is absent from the Anopheles gambiae genome. The intron-exon structures of the genes found so far suggest that the ancestral gene (before the duplication which gave rise to Amyrel) had two introns, and that subsequent, repeated and independent loss of one or both introns occurred in some Muscomorpha families. It seems that the Amyrel protein has experienced specific amino acid substitutions in regions generally well conserved in amylases, raising the possibility of peculiar, functional adaptations of this protein.

Amino Acid Motifs↗
PubMed2025

Analysis of duplication and possible sub-functionalization of wing gene network components in pea aphids.

A fundamental focus of evolutionary-developmental biology is uncovering the genetic mechanisms responsible for the gain and loss of characters. One approach to this question is to investigate changes in the coordinated expression of a group of genes important for the development of a character of interest (a gene regulatory network). Here we consider the possibility that modifications to the wing gene regulatory network (wGRN), as defined by work primarily done in Drosophila melanogaster, were involved in the evolution of wing dimorphisms of the pea aphid (Acyrthosiphon pisum). We hypothesize that this may have occurred via changes in expression levels or duplication followed by sub-functionalization of wGRN components. To test this, we annotated members of the wGRN in the pea aphid genome and assessed their expression levels in first and third nymphal instars of winged and wingless morphs of males and asexual females. We find that only two of the 32 assessed genes exhibit morph-biased expression. We also find that three wing genes (apterous (ap), warts (wts), and decapentaplegic (dpp)) have undergone gene duplication. In each case, the resulting paralogs show signs of functional divergence, exhibiting either sex-, morph-, or stage-specific expression. Two gene duplicates, wts2 and dpp3, are of particular interest with respect to wing dimorphism, as they exhibit a wingless male-specific isoform and wingless male-biased expression, respectively. These results supplement our understanding of trends in developmental gene network evolution, such as side-stepping pleiotropic constraint via duplication and sub-functionalization, underlying the emergence of novel phenotypes.

dimorphism↗
PubMed2001

Disruption of individual members of Arabidopsis syntaxin gene families indicates each has essential functions.

Syntaxins are a large group of proteins found in all eukaryotes involved in the fusion of transport vesicles to target membranes. Twenty-four syntaxins grouped into 10 gene families are found in the model plant Arabidopsis thaliana, each group containing one to five paralogous members. The Arabidopsis SYP2 and SYP4 gene families contain three members each that share 60 to 80% protein sequence identity. Gene disruptions of the yeast (Saccharomyces cerevisiae) orthologs of the SYP2 and SYP4 gene families (Pep12p and Tlg2p, respectively) indicate that these syntaxins are not essential for growth in yeast. However, we have isolated and characterized gene disruptions in two genes from each family, finding that disruption of individual syntaxins from these families is lethal in the male gametophyte of Arabidopsis. Complementation of the syp21-1 gene disruption with its cognate transgene indicated that the lethality is linked to the loss of the single syntaxin gene. Thus, it is clear that each syntaxin in the SYP2 and SYP4 families serves an essential nonredundant function.

Arabidopsis↗
PubMed1999

TOM1 genes map to human chromosome 22q13.1 and mouse chromosome 8C1 and encode proteins similar to the endosomal proteins HGS and STAM.

The avian tom1 (target of myb 1) gene has been previously characterized from v-myb-transformed cells. We report here cloning of the human and mouse tom1 orthologs. Both genes are expressed ubiquitously, with the highest levels in skeletal muscle, brain, and intestines, as assessed by Northern blot and mRNA in situ hybridization. The N-terminal domain of the TOM1 protein shares similarity with HGS (hepatocyte growth factor-regulated tyrosine kinase substrate) and STAM (signal-transducing adaptor molecule), which are associated with vesicular trafficking at the endosome. A putative coiled-coil domain was also detected in the central part of the TOM1 protein. This domain structure suggests that TOM1 is another member of a family of genes implicated in the trafficking regulation of growth-factor-receptor complexes that are destined for degradation in the lysosome. We also show that a human paralog of TOM1 (TOM1-like gene 1) exists. Furthermore, we provide a transcription map over a 190-kb contig of the TOM1 region. This map includes its distal neighbors HMOX1 and MCM5 and two proximal novel genes, one of which is a HMG-box-containing gene (HMG2L1), and the other of unknown function. Using a genomic PAC clone, we demonstrate that the mouse Tom1 and Hmox1 genes are part of an as yet undescribed syntenic group between mouse chromosome 8C1 and human chromosome 22q13.1.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Genetic interactions of Hox genes in limb development: learning from compound mutants.

The recent generation of mice harboring multiple mutations in Hox genes has highlighted the role of these genes in controlling growth and patterning of the limb bud. The study of the phenotypes has not only revealed a complex network of genetic interactions among paralogous and non-paralogous Abdominal-B-related Hox genes but has also refined our understanding of their function.

Animals↗
PubMed2026

Comparative analysis of genomic variations among different Cdo1 paralogs for salinity-adaptation in oysters.

Under rapid climate change and anthropogenic activities, oysters, a global aquaculture species, are subjected to exacerbated culturing environments, especially for those living in in-shore estuarine species, such as Suminoe oysters Crassostrea ariakensis. This study aims to investigate the molecular mechanisms of salinity adaptation of C. ariakensis. We performed an expression genome-wide association study (eGWAS) to compare genetic regulation among 5 paralogous copies of a key salinity-related gene, cysteine dioxygenase 1 (Cdo1). A total of 40 significant eSNPs with 82 adjacent eGenes were identified in 2 copies (Cdo1_26639 and Cdo1_1666). We identified only trans-eSNPs for Cdo1_26639 and more cis-eSNPs for Cdo1_1666, and different eGenes for these 2 Cdo1 copies, which indicated that the expressional regulation of these paralogs may undergo distinct pathways. We identified 3 eGenes that exhibited identical expression patterns with Cdo1_26639 and Cdo1_1666, including 6-Pgdh, Trapp and tandem copy of Cdo1_27337. The expression correlation between Cdo1 copies and eGenes was enhanced under salinity stresses, suggesting the crucial role of eGenes in regulating Cdo1's expression in response to salinity changes. Our results provide comprehensive identification and comparison of eSNPs across different paralogous copies of one gene, along with insights into the molecular mechanisms underlying salinity tolerance, and genetic markers for breeding salinity-resistant oysters.

Animals↗
PubMed1998

Genomic structure and sequence analysis of human HOXA-9.

In order to understand the regulatory mechanisms establishing and maintaining HOXA-9 gene expression, structural information about the gene is a prerequisite. Therefore, we sequenced the 7.2-kb region of the human HOXA-9 gene and mapped the positions of two partial cDNAs consisting of one of two 5' exons, AB (358 bp) or CD (568 bp), and a common 3' exon (exon II), which are separated by 5.4- and 1.0-kb introns, respectively. When the amino acid sequence homologies were compared with those of other Hox genes belonging to the same paralogous group, exon CD exhibited the strongest homology: 73% of 91 aa residues exactly matched those of chicken Hoxa-9. An intermediate exon (90 bp) was detected within exon CD. It was surrounded by a splice acceptor and a donor at both the 5' and 3' ends, and one branchpoint site was found near the splice-acceptor site. Nucleotide sequence analysis along this region revealed two TATA boxes, one CAAT box, one GC box, and one each of the following binding sites--engrailed, eve-stripe2-hb3, and Krox20--just upstream of exon CD. A CpG island and two RARE repeats were detected within intron I. Northern blot analysis showed that at least four main transcripts were generated along this region: all fetal tissues tested (brain, lung, liver, and kidney) produced a 1.8-kb homeobox-containing transcript (HA-9A); a 2.2- and a 3.3-kb transcript were generated from exon CD and exon II (HA-9B), especially in fetal and adult kidneys as well as in adult skeletal muscle; the 1.0-kb transcript was likely to be generated by the intermediate exon in all adult and fetal tissues. Several weak bands without tissue specificity were likely to be contributed by the hybrid transcripts between HOXA-9 and the other HOXA gene(s). Together, these results may account for the unique degree of conservation of the HOX cluster in general.

Adult↗
PubMed2005

A critical role of teashirt for patterning the ventral epidermis is masked by ectopic expression of tiptop, a paralog of teashirt in Drosophila.

The teashirt gene encodes a protein with three widely spaced zinc finger motifs that is crucial for specifying trunk identity in Drosophila embryos. Here, we describe a gene called tiptop, which encodes a protein highly similar to Teashirt. We have analyzed the expression patterns and functions of these two genes in the trunk of the embryo. Initially, teashirt and tiptop expressions are detected in distinct domains; teashirt in the trunk and tiptop in parts of the head and tail. In different mutant situations, we show that, in the trunk and head, they repress each other's expression. Unlike teashirt, we found that deletion of tiptop is homozygous viable and fertile. However, embryos lacking both gene activities display a more severe trunk phenotype than teashirt mutant embryos alone. Ectopic expression of either gene produces an almost identical phenotype, indicating that Teashirt and Tiptop have, on the whole, common activities. We conclude that Teashirt and Tiptop repress each other's expression and that Teashirt has a crucial role for trunk patterning that is in part masked by ectopic expression of Tiptop.

Amino Acid Sequence↗