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PubMed1993

Role of gene order in developmental control of human gamma- and beta-globin gene expression.

To determine the effect of gene order on globin gene developmental regulation, we produced transgenic mice containing two tandemly arranged gamma- or beta-globin or gamma beta- and beta gamma-globin genes linked to a 2.5-kb cassette containing sequences of the locus control region (LCR). Analysis of constructs containing two identical gamma or beta genes assessed the effect of gene order on globin gene expression, while analysis of constructs containing tandemly arranged gamma and beta genes assessed any additional effects of the trans-acting environment. When two gamma genes were tandemly linked to the LCR, expression from the proximal gamma gene was three- to fourfold higher than expression from the distal gamma gene, and the ratio of proximal to distal gene expression remained unchanged throughout development. Similarly, when two beta genes were tandemly linked to the LCR, the proximal beta gene was predominantly expressed throughout development. These results indicate that proximity to LCR increases gene expression, perhaps by influencing the frequency of interaction between the LCR and globin gene promoters. An arrangement where the gamma gene was proximal and the beta gene distal to the LCR resulted in predominant gamma-gene expression in the embryo. When the order was reversed and the gamma gene was placed distally to the LCR, gamma-gene expression in the embryo was still up to threefold higher than expression of the LCR-proximal beta gene. These findings suggest that the embryonic trans-acting environment interacts preferentially with the gamma genes irrespective of their order or proximity to the LCR. We conclude that promoter competition rather than gene order plays the major role in globin gene switching.

Animals↗

PubMed1992

Molecular characterization of phocine distemper virus: gene order and sequence of the gene encoding the attachment (H) protein.

Generation of a set of cDNA clones covering the N, P/V/C, M, F, H and part of the L gene of phocine distemper virus (PDV) has been described. The gene order of PDV determined from a physical as well as a transcriptional map, was identical to that of the other morbilliviruses so far studied. The H gene sequence (1951 nucleotides) contains one large open reading frame which encodes a protein of 607 amino acids, identical in length to that of the H protein of the Convac strain of canine distemper virus (CDV). Nucleotide and protein sequence comparisons between PDV and the other morbilliviruses provide further evidence in favour of PDV's inclusion in the morbillivirus genus as a distinct species closely related to CDV and more distantly to measles virus and rinderpest virus.

Amino Acid Sequence↗

PubMed2006

Visualizing syntenic relationships among the hemiascomycetes with the Yeast Gene Order Browser.

The Yeast Gene Order Browser (YGOB) is an online tool designed to facilitate the comparative genomic visualization and appraisal of synteny within and between the genomes of seven hemiascomycete yeast species. Three of these genomes are polyploid, and hence contain intra-genomic syntenic regions, the correct assembly of which is a particular success of YGOB. Designed to accurately assemble, display and score gene order relationships, YGOB is both an interactive tool for browsing genomic data, and a software engine now being used for evolutionary analyses on a whole-genome scale. Underlying the online interface is the YGOB database, which consists of homology assignments across the species, extensively curated based on sequence similarity and novelly, an appraisal of genomic context (synteny) in multiple genomes. Currently the YGOB database incorporates genome data from Saccharomyces cerevisiae, Candida glabrata, Saccharomyces castellii, Ashbya gossypii, Kluyveromyces lactis, Kluyveromyces waltii and Saccharomyces kluyveri, but the system is scaleable to accommodate additional genomes. This paper discusses the usage and utility of version 1.0 of YGOB, which is publicly available at http://wolfe.gen.tcd.ie/ygob.

Chromosomes, Fungal↗

PubMed2005

Gene order in plants: a slow but sure shuffle.

Comparative mapping studies have revealed a great deal about the patterns of gene order and gene content evolution in plants. These findings have practical importance for leveraging genomic information from model to nonmodel plant species. However, there is much to be learned about the processes by which gene order and content evolve. The role of gene duplication and loss in the evolution of plant gene order, in particular, appears to be more important than commonly appreciated. An exciting area of current research is the study of gene order and content polymorphism within species. Some recent findings suggest that there may be a functional, and adaptive, relationship between gene order and phenotype that is mediated by the effects of gene order on transcriptional regulation.

Biological Evolution↗

PubMed2001

Evolution of gene order conservation in prokaryotes.

BACKGROUND: As more complete genomes are sequenced, conservation of gene order between different organisms is emerging as an informative property of the genomes. Conservation of gene order has been used for predicting function and functional interactions of proteins, as well as for studying the evolutionary relationships between genomes. The reasons for the maintenance of gene order are still not well understood, as the organization of the prokaryote genome into operons and lateral gene transfer cannot possibly account for all the instances of conservation found. Comprehensive studies of gene order are one way of elucidating the nature of these maintaining forces. RESULTS: Gene order is extensively conserved between closely related species, but rapidly becomes less conserved among more distantly related organisms, probably in a cooperative fashion. This trend could be universal in prokaryotic genomes, as archaeal genomes are likely to behave similarly to bacterial genomes. Gene order conservation could therefore be used as a valid phylogenetic measure to study relationships between species. Even between very distant species, remnants of gene order conservation exist in the form of highly conserved clusters of genes. This suggests the existence of selective processes that maintain the organization of these regions. Because the clusters often span more than one operon, common regulation probably cannot be invoked as the cause of the maintenance of gene order. CONCLUSIONS: Gene order conservation is a genomic measure that can be useful for studying relationships between prokaryotes and the evolutionary forces shaping their genomes. Gene organization is extensively conserved in some genomic regions, and further studies are needed to elucidate the reason for this conservation.

Conserved Sequence↗

PubMed2006

Metabolic engineering of carotenoid biosynthesis in Escherichia coli by ordered gene assembly in Bacillus subtilis.

We attempted to optimize the production of zeaxanthin in Escherichia coli by reordering five biosynthetic genes in the natural carotenoid cluster of Pantoea ananatis. Newly designed operons for zeaxanthin production were constructed by the ordered gene assembly in Bacillus subtilis (OGAB) method, which can assemble multiple genes in one step using an intrinsic B. subtilis plasmid transformation system. The highest level of production of zeaxanthin in E. coli (820 microg/g [dry weight]) was observed in the transformant with a plasmid in which the gene order corresponds to the order of the zeaxanthin metabolic pathway (crtE-crtB-crtI-crtY-crtZ), among a series of plasmids with circularly permuted gene orders. Although two of five operons using intrinsic zeaxanthin promoters failed to assemble in B. subtilis, the full set of operons was obtained by repressing operon expression during OGAB assembly with a p(R) promoter-cI repressor system. This result suggests that repressing the expression of foreign genes in B. subtilis is important for their assembly by the OGAB method. For all tested operons, the abundance of mRNA decreased monotonically with the increasing distance of the gene from the promoter in E. coli, and this may influence the yield of zeaxanthin. Our results suggest that rearrangement of biosynthetic genes in the order of the metabolic pathway by the OGAB method could be a useful approach for metabolic engineering.

Bacillus subtilis↗

PubMed1988

Different mitochondrial gene orders among insects: exchanged tRNA gene positions in the COII/COIII region between an orthopteran and a dipteran species.

We have cloned and sequenced a 2.65 kb segment of the mtDNA molecule of the orthopteran insect Locusta migratoria. It harbors the genes for four mitochondrial tRNAs, for cytochrome c oxidase subunits II and III and for ATPase subunits 6 and 8. The order of the locust genes resembles that of Drosophila yakuba: in both insects the genes for COII and ATPase 8 are separated from each other by the genes encoding tRNA(lys) and tRNA(asp), but in the locust, the positions of the two tRNA genes are reversed. This leads to a different mitochondrial gene order in the two insects.

Amino Acid Sequence↗

PubMed2000

Early eukaryote evolution based on mitochondrial gene order breakpoints.

The comparison of the gene orders in a set of genomes can be used to infer their phylogenetic relationships and to reconstruct ancestral gene orders. For three genomes this is done by solving the "median problem for breakpoints"; this solution can then be incorporated into a routine for estimating optimal gene orders for all the ancestral genomes in a fixed phylogeny. For the difficult (and most prevalent) case where the genomes contain partially different sets of genes, we present a general heuristic for the median problem for induced breakpoints. A fixed-phylogeny optimization based on this is applied in a phylogenetic study of a set of completely sequenced protist mitochondrial genomes, confirming some of the recent sequence-based groupings which have been proposed and, conversely, confirming the usefulness of the breakpoint method as a phylogenetic tool even for small genomes.

Biological Evolution↗

PubMed1998

Multiple independent origins of mitochondrial gene order in birds.

Mitochondrial genomes of all vertebrate animals analyzed to date have the same 37 genes, whose arrangement in the circular DNA molecule varies only in the relative position of a few genes. This relative conservation suggests that mitochondrial gene order characters have potential utility as phylogenetic markers for higher-level vertebrate taxa. We report discovery of a mitochondrial gene order that has had multiple independent originations within birds, based on sampling of 137 species representing 13 traditionally recognized orders. This provides evidence of parallel evolution in mitochondrial gene order for animals. Our results indicate operation of physical constraints on mitochondrial gene order changes and support models for gene order change based on replication error. Bird mitochondria have a displaced OL (origin of light-strand replication site) as do various other Reptilia taxa prone to gene order changes. Our findings point to the need for broad taxonomic sampling in using mitochondrial gene order for phylogenetic analyses. We found, however, that the alternative mitochondrial gene orders distinguish the two primary groups of songbirds (order Passeriformes), oscines and suboscines, in agreement with other molecular as well as morphological data sets. Thus, although mitochondrial gene order characters appear susceptible to some parallel evolution because of mechanistic constraints, they do hold promise for phylogenetic studies.

Journal Article↗

PubMed2006

Unusual gene order and organization of the sea urchin hox cluster.

While the highly consistent gene order and axial colinear patterns of expression seem to be a feature of vertebrate hox gene clusters, this pattern may be less well conserved across the rest of the bilaterians. We report the first deuterostome instance of an intact hox cluster with a unique gene order where the paralog groups are not expressed in a sequential manner. The finished sequence from BAC clones from the genome of the sea urchin, Strongylocentrotus purpuratus, reveals a gene order wherein the anterior genes (Hox1, Hox2 and Hox3) lie nearest the posterior genes in the cluster such that the most 3' gene is Hox5. (The gene order is 5'-Hox1, 2, 3, 11/13c, 11/13b, 11/13a, 9/10, 8, 7, 6, 5-3'.) The finished sequence result is corroborated by restriction mapping evidence and BAC-end scaffold analyses. Comparisons with a putative ancestral deuterostome Hox gene cluster suggest that the rearrangements leading to the sea urchin gene order were many and complex.

Animals↗

PubMed2006

Significant gene order and expression differences in Bordetella pertussis despite limited gene content variation.

Bordetella pertussis, an obligate human pathogen and the agent of whooping cough, is a clonal species, despite the dynamic selection pressures imposed by host immunity and vaccine usage. Because the generation of variation is critical for species evolution, we employed a variety of approaches to examine features of B. pertussis genetic variation. We found a high level of conservation of gene content among 137 B. pertussis strains with different geographical, temporal, and epidemiological associations, using comparative genomic hybridization. The limited number of regions of difference were frequently located adjacent to copies of the insertion element IS481, which is present in high numbers in the B. pertussis chromosome. This repeated sequence appears to provide targets for homologous recombination, resulting in deletion of intervening sequences. Using subtractive hybridization, we searched for previously undetected genes in diverse clinical isolates but did not detect any new genes, indicating that gene acquisition is rare in B. pertussis. In contrast, we found evidence of altered gene order in the several strains that were examined and again found an association of IS481 with sites of rearrangement. Finally, we compared whole-genome expression profiles of different strains and found significant changes in transcript abundance, even in the same strain after as few as 12 laboratory passages. This combination of approaches provides a detailed picture of a pathogenic species with little gene loss or gain but with the capacity to generate variation by rearranging its chromosome and altering gene expression. These findings have broad implications for host adaptation by microbial pathogens.

Bordetella pertussis↗

PubMed1987

Evolutionary relationships between catabolic pathways for aromatics: conservation of gene order and nucleotide sequences of catechol oxidation genes of pWW0 and NAH7 plasmids.

TOL plasmid pWW0 and plasmid NAH7 encode catabolic enzymes required for oxidative degradation of toluene and naphthalene, respectively. The gene order of the catabolic operon of NAH7 for salicylate oxidation was determined to be: promoter--nahG (the structural gene for salicylate hydroxylase)--nahH (catechol 2.3-dioxygenase)--nahI (hydroxymuconic semialdehyde dehydrogenase)--nahN (hydroxymuconic semialdehyde hydrolase)--nahL (2-oxopent-4-enoate hydratase). This order is identical to that of the isofunctional genes of TOL plasmid pWW0. The complete nucleotide sequence of nahH was determined and compared with that of xylE, the isofunctional gene of TOL plasmid pWW0. There were 20% and 16% differences in their nucleotide and amino acid sequences, respectively. The homology between the NAH7 and TOL pWW0 plasmids ends upstream of the Shine-Dalgarno sequences of nahH and xylE, but the homology continues downstream of these genes. This observation suggested that genes for the catechol oxidative enzymes of NAH7 and TOL pWW0 were derived from a common ancestral sequence which was transferred as a discrete segment of DNA between plasmids.

Amino Acid Sequence↗

PubMed2000

Conservation of gene order amongst cell wall and cell division genes in Eubacteria, and ribosomal genes in Eubacteria and Eukaryotic organelles.

Comparison of genome sequences from Eubacteria and Eukaryotic organelles shows that the order of genes in gene clusters encoding certain highly conserved cell division proteins and ribosomal proteins is itself highly conserved. Experiments with a cluster of cell division and related genes of E. coli have shown that this gene order is not essential for function. Comparisons between genomes also show that no pair of genes are necessarily adjacent in all genomes. The reason for the extreme conservation of order is therefore unknown, although one possible explanation might be the lateral exchange of tightly-linked groups of genes coding for co-adapted sets of proteins.

Bacteria↗

PubMed2006

The complete mitochondrial genome of the common sea slater, Ligia oceanica (Crustacea, Isopoda) bears a novel gene order and unusual control region features.

BACKGROUND: Sequence data and other characters from mitochondrial genomes (gene translocations, secondary structure of RNA molecules) are useful in phylogenetic studies among metazoan animals from population to phylum level. Moreover, the comparison of complete mitochondrial sequences gives valuable information about the evolution of small genomes, e.g. about different mechanisms of gene translocation, gene duplication and gene loss, or concerning nucleotide frequency biases. The Peracarida (gammarids, isopods, etc.) comprise about 21,000 species of crustaceans, living in many environments from deep sea floor to arid terrestrial habitats. Ligia oceanica is a terrestrial isopod living at rocky seashores of the european North Sea and Atlantic coastlines. RESULTS: The study reveals the first complete mitochondrial DNA sequence from a peracarid crustacean. The mitochondrial genome of Ligia oceanica is a circular double-stranded DNA molecule, with a size of 15,289 bp. It shows several changes in mitochondrial gene order compared to other crustacean species. An overview about mitochondrial gene order of all crustacean taxa yet sequenced is also presented. The largest non-coding part (the putative mitochondrial control region) of the mitochondrial genome of Ligia oceanica is unexpectedly not AT-rich compared to the remainder of the genome. It bears two repeat regions (4x 10 bp and 3x 64 bp), and a GC-rich hairpin-like secondary structure. Some of the transfer RNAs show secondary structures which derive from the usual cloverleaf pattern. While some tRNA genes are putative targets for RNA editing, trnR could not be localized at all. CONCLUSION: Gene order is not conserved among Peracarida, not even among isopods. The two isopod species Ligia oceanica and Idotea baltica show a similarly derived gene order, compared to the arthropod ground pattern and to the amphipod Parhyale hawaiiensis, suggesting that most of the translocation events were already present the last common ancestor of these isopods. Beyond that, the positions of three tRNA genes differ in the two isopod species. Strand bias in nucleotide frequency is reversed in both isopod species compared to other Malacostraca. This is probably due to a reversal of the replication origin, which is further supported by the fact that the hairpin structure typically found in the control region shows a reversed orientation in the isopod species, compared to other crustaceans.

Animals↗

PubMed2001

Evolution of gene order in the genomes of two related yeast species.

Changes in gene order between the genomes of two related yeast species, Saccharomyces cerevisiae and Saccharomyces bayanus var. uvarum were studied. From the dataset of a previous low coverage sequencing of the S. bayanus var. uvarum genome, 35 different synteny breakpoints between neighboring genes and two cases of local gene inversion were characterized in detail. The number and the type of the chromosomal rearrangements that have led to these differences were identified. We show that evolution of gene order in the genomes of these two yeast species is driven mainly by gene duplication onto different chromosomes followed by differential loss of the repeated copies. In addition, local gene inversions also would result from a mechanism of gene duplication, but in an inverted orientation, followed by loss of the original copy. The identification of traces of anciently duplicated genes, called relics, show that the loss of duplicates is more frequently caused by the accumulation of numerous mutations in one of the two copies than by DNA deletion. Surprisingly, gross chromosomal rearrangements such as translocations have only a minor effect on gene order reshuffling as they account for <10% of the synteny breakpoints.

Chromosome Inversion↗

PubMed2001

Evolution of prokaryotic gene order: genome rearrangements in closely related species.

Conservation of gene order in prokaryotes has become important in predicting protein function because, over the evolutionary timescale, genomes are shuffled so that local gene-order conservation reflects the functional constraints within the protein. Here, we compare closely related genomes to identify the rate with which gene order is disrupted and to infer the genes involved in the genome rearrangement.

Evolution, Molecular↗

PubMed2005

A hotspot of gene order rearrangement by tandem duplication and random loss in the vertebrate mitochondrial genome.

Most reported examples of change in vertebrate mitochondrial (mt) gene order could be explained by a tandem duplication followed by random loss of redundant genes (tandem duplication-random loss [TDRL] model). Under this model of evolution, independent loss of genes arising from a single duplication in an ancestral species are predicted, and remnant pseudogenes expected, intermediate states that may remain in rearranged genomes. However, evidence for this is rare and largely scattered across vertebrate lineages. Here, we report new derived mt gene orders in the vertebrate "WANCY" region of four closely related caecilian amphibians. The novel arrangements found in this genomic region (one of them is convergent with the derived arrangement of marsupials), presence of pseudogenes, and positions of intergenic spacers fully satisfy predictions from the TDRL model. Our results, together with comparative data for the available vertebrate complete mt genomes, provide further evidence that the WANCY genomic region is a hotspot for gene order rearrangements and support the view that TDRL is the dominant mechanism of gene order rearrangement in vertebrate mt genomes. Convergent gene rearrangements are not unlikely in hotspots of gene order rearrangement by TDRL.

Amphibians↗

PubMed1988

Cloning and physical mapping of RNA polymerase genes from Methanobacterium thermoautotrophicum and comparison of homologies and gene orders with those of RNA polymerase genes from other methanogenic archaebacteria.

The structural genes encoding the four largest subunits of RNA polymerase, A, B', B", and C, were physically mapped in Methanobacterium thermoautotrophicum Winter. The genes formed a cluster in the order B", B', A, C and had a common orientation. DNA hybridization experiments yielded different degrees of homology between RNA polymerase gene sequences of different species of Methanobacterium and Methanococcus voltae. No homology was detectable between Methanobacterium thermoautotrophicum and Methanosarcina barkeri. From Southern hybridization experiments in which probes of the four genes from Methanobacterium thermoautotrophicum Winter and restriction digests of the genomic DNAs of the different methanogens were used, a common gene order of the RNA polymerase genes could be deduced.

Archaea↗