Evolution and expression of vitellogenin genes.
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Amino Acid Sequence↗
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Nucleotide sequence of phospholipase A(2) gene expressed in snake pancreas reveals the molecular evolution of toxic phospholipase A(2) genes.
We have cloned two phospholipase A(2) (PLA(2)) DNA complementary to RNA that contained nucleotide sequences encoding pancreas loop by the reverse transcription-polymerase chain reaction cloning procedure using messenger RNA isolated from Laticauda semifasciata pancreas. Additionally, a gene clone encoding PLA(2) with the pancreatic loop sequence was isolated from a L. semifasciata genomic library. Subsequent sequence analysis revealed that PLA(2) clones encoding group IB" PLA(2). Comparative analysis of group IA and IB" PLA(2) genes revealed that the exon-intron organization is conserved in the genes of both groups. The invaded sequences in the second intron were very similar to those of the L. semifasciata group IA gene. This observation suggested that the integration of the invaded sequences occurred before the divergence of groups IA and IB" during the evolution of PLA(2) gene. The comparative analysis revealed that the arising of group IA PLA(2) occurred by the deletion and substitution of nucleotide sequences in exon III region during the process of accelerated evolution.
Amino Acid Sequence↗
Human and mouse lactate dehydrogenase genes A (muscle), B (heart), and C (testis): protein structure, genomic organization, regulation of expression, and molecular evolution.
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Amino Acid Sequence↗
The prepro vasoactive intestinal contractor (VIC)/endothelin-2 gene (EDN2): structure, evolution, production, and embryonic expression.
Murine vasoactive intestinal contractor (VIC) and its human analog endothelin-2 (ET2) are potent vasoactive hormones composed of 21 amino acids. To study the structural characteristics of the VIC/ET2 gene (HGMW-approved symbol EDN2), we isolated the full length of the mouse VIC gene. Sequence analysis indicates that a biologically active mature VIC peptide is produced from a 175-residue precursor protein; preproVIC (PPVIC). Several remarkable similarities of the PPVIC gene to the human preproendothelin-1 gene strongly suggest that the two genes have arisen from a common progenitor by gene duplication. Transfection of ACHN adenocarcinoma cells with the cDNA resulted in the production of VIC peptide. VIC production was increased by the deletion of the 3'-untranslated region, which contains an AU-rich mRNA destabilizing sequence. Increased PPVIC gene expression during the late embryonic stage suggests an important function in development. This study provides the basis for disruption and regulation analysis of the gene, which may lead to a better understanding of VIC/ET2's physiological significance.
Amino Acid Sequence↗
Evolution and developmental expression of nuclear receptor genes in the ascidian Herdmania.
Nuclear receptors are a superfamily of metazoan transcription factors that have been shown to be involved in a wide range of developmental and physiological processes. A PCR-based survey of genomic DNA and developmental cDNAs from the ascidian Herdmania identifies eight members of this multigene family. Sequence comparisons and phylogenetic analyses reveal that these ascidian nuclear receptors are representative of five of the six previously defined nuclear receptor subfamilies and are apparent homologues of retinoic acid [NR1B], retinoid X [NR2B], peroxisome proliferator-activated [NR1C], estrogen related [NR3B], neuron-derived orphan (NOR) [NR4A3], nuclear orphan [NR4A], TR2 orphan [NR2C1] and COUP orphan [NR2F3] receptors. Phylogenetic analyses that include the ascidian genes produce topologically distinct trees that suggest a redefinition of some nuclear receptor subfamilies. These trees also suggest that extensive gene duplication occurred after the vertebrates split from invertebrate chordates. These ascidian nuclear receptor genes are expressed differentially during embryogenesis and metamorphosis.
Amino Acid Sequence↗
Stochastic modeling of single-cell gene expression adaptation reveals non-genomic contribution to evolution of tumor subclones.
Cancer progression is an evolutionary process driven by the selection of cells adapted to gain growth advantage. We present a formal study on the adaptation of gene expression in subclonal evolution. We model evolutionary changes in gene expression as stochastic Ornstein-Uhlenbeck processes, jointly leveraging the evolutionary history of subclones and single-cell expression data. Applying our model to sublines derived from single cells of a mouse melanoma revealed that sublines with distinct phenotypes are underlined by different patterns of gene expression adaptation, indicating non-genetic mechanisms of cancer evolution. Sublines previously observed to be resistant to anti-CTLA4 treatment showed adaptive expression of genes related to invasion and non-canonical Wnt signaling, whereas sublines that responded to treatment showed adaptive expression of genes related to proliferation and canonical Wnt signaling. Our results suggest that clonal phenotypes emerge as the result of specific adaptivity patterns of gene expression. A record of this paper's transparent peer review process is included in the supplemental information.
Animals↗
Evolution by gene duplication revisited: differentiation of regulatory elements versus proteins.
For evolution by gene duplication, differentiation of both regulatory elements and proteins is important. Particularly the former is thought to have large effects on morphological evolution, since differential expression of genes is essential for development. In this report, recent knowledge on regulatory elements is reviewed that is relevant to the population genetics aspects of gene duplication. Regulatory elements usually consist of multiple binding sites of two or more transcription factors. The amount of gene product is quantitatively regulated, and is thought to be subject to stabilizing selection. The intensity of stabilizing selection depends upon the level of constraint imposed by regulatory networks. Gene duplication has significant effects on stabilizing selection via perturbation of gene expression. It is pointed out that constraints coming from regulatory networks are most important for survival of duplicate genes, and that both drift and selection are at work in the process of acquisition of new gene expression and function.
Evolution, Molecular↗
The phenylalanine ammonia-lyase gene family in raspberry. Structure, expression, and evolution.
In raspberry (Rubus idaeus), development of fruit color and flavor are critically dependent on products of the phenylpropanoid pathway. To determine how these metabolic functions are integrated with the fruit ripening program, we are examining the properties and expression of key genes in the pathway. Here, we report that L- phenylalanine ammonia-lyase (PAL) is encoded in raspberry by a family of two genes (RiPAL1 and RiPAL2). RiPAL1 shares 88% amino acid sequence similarity to RiPAL2, but phylogenetic analysis places RiPAL1 and RiPAL2 in different clusters within the plant PAL gene family. The spatial and temporal expression patterns of the two genes were investigated in various vegetative and floral tissues using the reverse transcriptase competitor polymerase chain reaction assay. Although expression of both genes was detected in all tissues examined, RiPAL1 was associated with early fruit ripening events, whereas expression of RiPAL2 correlated more with later stages of flower and fruit development. Determination of the absolute levels of the two transcripts in various tissues showed that RiPAL1 transcripts were 3- to 10-fold more abundant than those of RiPAL2 in leaves, shoots, roots, young fruits, and ripe fruits. The two RiPAL genes therefore appear to be controlled by different regulatory mechanisms.
Acyltransferases↗
Wnt gene expression in sea urchin development: heterochronies associated with the evolution of developmental mode.
The Wnt genes encode a large family of conserved secreted proteins that are widely involved in animal development. The variety and ubiquity of this ancient family suggest that Wnt genes may have been important in the evolution of animal development, including early development. To test this hypothesis, we have characterized the expression of several Wnt genes in closely related sea urchins that exhibit radically different modes of early development. Wnt-1, -4, and -5 genes exhibit several conserved molecular and developmental characteristics, both within sea urchins and with Wnt genes examined in other animals (Ferkowicz et al. 1998). Here, we demonstrate that sea urchin Wnt-5 transcripts are specifically detected by in situ hybridization in discrete embryonic, larval, and developing adult tissues and processes: (1) in a band of vegetal ectoderm in mesenchyme blastula stage embryos, (2) in the larval ciliary bands, (3) in tissues that form the early adult rudiment (left coelomic pouch and overlying vestibular ectoderm), and (4) in the developing adult radial nervous system. We find that the sites of Wnt-5 transcript accumulation are conserved in species exhibiting either indirect- or direct-developmental modes, suggesting that Wnt-5 function(s) have been conserved in sea urchin development. However, dramatic heterochronic changes in Wnt-5 gene expression have occurred in the direct-developing species that parallel the accelerated morphological changes that occur during direct development. These results suggest that heterochronic changes in the expression of conserved developmental regulatory genes, such as the Wnt family members, are agents of evolutionary change in animal development.
Animals↗
Odorant receptor gene regulation: implications from genomic organization.
Odorant receptor genes comprise the largest known family of G-protein-coupled receptors in vertebrates. These receptor genes are tightly clustered in the genomes of every vertebrate organism investigated, including zebrafish, mice and humans, and they appear to have expanded and duplicated throughout evolution. In a mechanism that has yet to be elucidated, each olfactory neuron expresses a single receptor gene. This highly restricted expression pattern underlies the ability to distinguish between a wide variety of odorants. Here, we address the evolutionary expansion of odorant receptor genes and the role genomic organization of these genes might have in their tightly regulated expression.
Alleles↗
The carcinoembryonic antigen gene family: structure, expression and evolution.
The molecular cloning of carcinoembryonic antigen (CEA) and several cross-reacting antigens reveals a basic domain structure for the whole family, which shows structural similarities to the immunoglobulin superfamily. The CEA family consists of approximately 10 genes which are localized in two clusters on chromosome 19. So far, mRNA species for five of these genes have been identified which show tissue variability in their transcriptional activity. Expression of some of these genes in heterologous systems has been achieved, allowing the localization of some epitopes. The characterization of a CEA gene family in the rat and a comparison with its human counterpart has been utilized in the development of an evolutionary model.
Amino Acid Sequence↗
Expression and evolution of functionally distinct haemoglobin genes in plants.
Haemoglobin genes have been found in a number of plant species, but the number of genes known has been too small to allow effective evolutionary inferences. We present nine new non-symbiotic haemoglobin sequences from a range of plants, including class 1 haemoglobins from cotton, Citrus and tomato, class 2 haemoglobins from cotton, tomato, sugar beet and canola and two haemoglobins from the non-vascular plants, Marchantia polymorpha (a liverwort) and Physcomitrella patens (a moss). Our molecular phylogenetic analysis of all currently known non-symbiotic haemoglobin genes and a selection of symbiotic haemoglobins have confirmed the existence of two distinct classes of haemoglobin genes in the dicots. It is likely that all dicots have both class 1 and class 2 non-symbiotic haemoglobin genes whereas in monocots we have detected only class 1 genes. The symbiotic haemoglobins from legumes and Casuarina are related to the class 2 non-symbiotic haemoglobins, whilst the symbiotic haemoglobin from Parasponia groups with the class 1 non-symbiotic genes. Probably, there have been two independent recruitments of symbiotic haemoglobins. Although the functions of the two non-symbiotic haemoglobins remain unknown, their patterns of expression within plants suggest different functions. We examined the expression in transgenic plants of the two non-symbiotic haemoglobins from Arabidopsis using promoter fusions to a GUS reporter gene. The Arabidopsis GLB1 and GLB2 genes are likely to be functionally distinct. The class 2 haemoglobin gene (GLB2) is expressed in the roots, leaves and inflorescence and can be induced in young plants by cytokinin treatment in contrast to the class 1 gene (GLB1) which is active in germinating seedlings and can be induced by hypoxia and increased sucrose supply, but not by cytokinin treatment.
Adenine↗
[Structure, expression and evolution of the genes for a photosynthetic apparatus: RuBisCO (fraction I protein) genes as a model system].
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Amino Acid Sequence↗
The organization, expression, and evolution of antibody genes and other multigene families.
The multigene family is a unit of chromosomal organization. Its gene members are closely linked, homologous in sequence, and have overlapping functions. Multigene families can be divided into three catagories: simple-sequence, multiplicational, and informational-by a variety of structural and functional criteria. Multigene families exhibit two novel evolutionary features-coincidental evolution and rapid change in family size-that suggest that they all share one or more evolutionary mechanisms. Natural selection cannot act directly upon individual genes in a family because of their identical or overlapping functions; hence selection must operate upon the family as a whole or upon blocks of genes within the family. The mechanism(s) for coincidental evolution expands out variant genes within a family so they can be acted upon by natural selection and, accordingly, permits multigene families to evolve adaptively. The control mechanisms in multiplicational families appear to promote the rapid expression of many gene copies. In contrast, the regulatory mechanisms of informational families promote the selection, expression, and amplification of appropriate units of information. The close linkage of the genes in a family appears to be a consequence of the fact that their control and evolutionary mechanisms may only operate on tandemly linked genes. New multigene families may evolve from a single gene or from other multigene families. In addition to evolving new functions, the latter mode of evolution generates a new multigene family whose members are preadapted to interact with those of the old family. These family interactions can lead to the evolution of more sophisticated molecular machines or to the regulation of one family by a second. Multigene families may be large or small. The three catagories of multigene families allow potential multigene families to be identified, and they suggest specific experimental approaches for the study of new families. Some of the most interesting genetic systems under the investigation today are known or potential informational multigene families. This is not fortuitous in that many of the most interesting aspects of phenotype are complex ones with correspondingly complex genetic, evolutionary, and regulatory requirements. One of the frontiers in modern genetics is the identification, characterization, and understanding of informational multigene families.
Alleles↗
The human acute-phase serum amyloid A gene family: structure, evolution and expression in hepatoma cells.
Serum amyloid A (SAA) proteins are a group of phylogenetically conserved acute-phase reactants. Evidence is presented here for the existence of four genetic loci for the human serum amyloid A (SAA) genes. The first locus was defined by three contiguous lambda clones spanning approximately 30 kb which contained a single SAA gene encoding apoSAA1 beta. Allelic variants were isolated at the second locus: a novel clone encoding apoSAA2 alpha was distinguished from SAA2 beta (previously known as SAAg9, Ref.1) by a His/Arg polymorphism at residue 71.SAA1 and SAA2 found in the high density lipoprotein fraction of acute-phase plasma were approximately 90% homologous at the nucleotide level. Homology in the 5' flanking regions was reflected functionally with similar transcriptional responses to inflammatory cytokines in transfected hepatoma cells. A further novel gene, SAA4, was isolated from a cosmid library and mapped 10 kb downstream of SAA2. The locus defining SAA3 has been described elsewhere. Polymorphisms were detected at both SAA1 and SAA2 loci by Southern analysis and the entire SAA region mapped to discrete fragments by pulsed field analysis. The four genes account for all the hybridizing bands present on Southern analyses in a Caucasian population.
Base Sequence↗
Systematic changes in gene expression patterns following adaptive evolution in yeast.
Culturing a population of Saccharomyces cerevisiae for many generations under conditions to which it is not optimally adapted selects for fitter genetic variants. This simple experimental design provides a tractable model of adaptive evolution under natural selection. Beginning with a clonal, founding population, independently evolved strains were obtained from three independent cultures after continuous aerobic growth in glucose-limited chemostats for more than 250 generations. DNA microarrays were used to compare genome-wide patterns of gene expression in the evolved strains and the parental strain. Several hundred genes were found to have significantly altered expression in the evolved strains. Many of these genes showed similar alterations in their expression in all three evolved strains. Genes with altered expression in the three evolved strains included genes involved in glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, and metabolite transport. These results are consistent with physiological observations and indicate that increased fitness is acquired by altering regulation of central metabolism such that less glucose is fermented and more glucose is completely oxidized.
Adaptation, Physiological↗
The single MyoD family gene of Ciona intestinalis encodes two differentially expressed proteins: implications for the evolution of chordate muscle gene regulation.
A MyoD family gene was identified in the ascidian Ciona intestinalis and designated CiMDF (Ciona intestinalis Muscle Determination Factor). Expression of CiMDF was restricted to the muscle cells of the developing embryo and the body-wall muscle of adults. Northern blots showed that two differentially regulated CiMDF transcripts were expressed during development. A 1.8 kb transcript (CiMDFa) appeared first and was gradually replaced by a 2.7 kb transcript (CiMDFb). These transcripts encoded essentially identical MyoD family proteins with the exception of a 68 amino acid C-terminal sequence present in CiMDFb that was absent from CiMDFa. Although both CiMDFa and CiMDFb contained the cysteine-rich/basic-helix loop helix domain (Cys-rich/bHLH) present in all MyoD family proteins, only CiMDFb contained the region near the C terminus (Domain III) characteristic of this gene family. Genomic Southern blots showed that C. intestinalis has only one MyoD family gene, suggesting that CiMDFa and CiMDFb result from differential processing of primary transcripts. The existence of two MyoD family proteins that are differentially expressed during ascidian embryogenesis has novel parallels to vertebrate muscle development and may reflect conserved myogenic regulatory mechanisms among chordates.
Amino Acid Sequence↗
Isolation, expression, and evolution of the gene encoding mitochondrial elongation factor Tu in Arabidopsis thaliana.
We have characterized a second nuclear gene (tufM) in Arabidopsis thaliana that encodes a eubacterial-like protein synthesis elongation factor Tu (EF-Tu). This gene does not closely resemble the previously described Arabidopsis nuclear tufA gene, which encodes the plastid EF-Tu, and does not contain sequence elements found in all cyanobacterial and plastid tufA genes. However, the predicted amino acid sequence includes an N-terminal extension which resembles an organellar targeting sequence and shares three unique sequence elements with mitochondrial EF-Tu's, from Saccharomyces cerevisiae and Homo sapiens, suggesting that this gene encodes the Arabidopsis mitochondrial EF-Tu. Consistent with this interpretation, the gene is expressed at a higher level in flowers than in leaves. Phylogenetic analysis confirms the mitochondrial character of the sequence and indicates that the human, yeast, and Arabidopsis tufM genes have undergone considerably more sequence divergence than their cytoplasmic counterparts, perhaps reflecting a cross-compartmental acceleration of gene evolution for components of the mitochondrial translation apparatus. As previously observed for tufA, the tufM gene is present in one copy in Arabidopsis but in several copies in other species of crucifers.
Amino Acid Sequence↗