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PubMed1998

Evolutionary relationships among the members of an ancient class of non-LTR retrotransposons found in the nematode Caenorhabditis elegans.

We took advantage of the massive amount of sequence information generated by the Caenorhabditis elegans genome project to perform a comprehensive analysis of a group of over 100 related sequences that has allowed us to describe two new C. elegans non-LTR retrotransposons. We named them Sam and Frodo. We also determined that several highly divergent subfamilies of both elements exist in C. elegans. It is likely that several master copies have been active at the same time in C. elegans, although only a few copies of both Sam and Frodo have characteristics that are compatible with them being active today. We discuss whether it is more appropriate under these circumstances to define only 2 elements corresponding to the most divergent groups of sequences or up to 16, considering each subfamily a different element. The C. elegans elements are related to other previously described non-LTR retrotransposons (CR1, found in different vertebrates; SR1, from the trematode Schistosoma; Q and T1, from the mosquito Anopheles). All of these elements, according to the analysis of their reverse transcriptases, form a monophyletic cluster that we call the "T1/CR1 subgroup." Elements of this subgroup are thus ancient components of the genome of animal species. However, we discuss the possibility that these elements may occasionally be horizontally transmitted.

Amino Acid Sequence↗
PubMed2004

Codon bias signatures, organization of microorganisms in codon space, and lifestyle.

New and simple numerical criteria based on a codon adaptation index are applied to the complete genomic sequences of 80 Eubacteria and 16 Archaea, to infer weak and strong genome tendencies toward content bias, translational bias, and strand bias. These criteria can be applied to all microbial genomes, even those for which little biological information is known, and a codon bias signature, that is the collection of strong biases displayed by a genome, can be automatically derived. A codon bias space, where genomes are identified by their preferred codons, is proposed as a novel formal framework to interpret genomic relationships. Principal component analysis confirms that although GC content has a dominant effect on codon bias space, thermophilic and mesophilic species can be identified and separated by codon preferences. Two more examples concerning lifestyle are studied with linear discriminant analysis: suitable separating functions characterized by sets of preferred codons are provided to discriminate: translationally biased (hyper)thermophiles from mesophiles, and organisms with different respiratory characteristics, aerobic, anaerobic, facultative aerobic and facultative anaerobic. These results suggest that codon bias space might reflect the geometry of a prokaryotic "physiology space." Evolutionary perspectives are noted, numerical criteria and distances among organisms are validated on known cases, and various results and predictions are discussed both on methodological and biological grounds.

Adaptation, Biological↗
PubMed1990

Equine herpesvirus type 1 unique short fragment encodes glycoproteins with homology to herpes simplex virus type 1 gD, gI and gE.

The nucleotide sequence of a 6.4 kbp portion of the 10.6 kbp BamHI fragment D contained in the unique short region of the equine herpesvirus type 1 (EHV-1) genome has been determined. Analysis of this sequence revealed five open reading frames (ORFs), four complete and one incomplete, which were encoded by the same sense strand. Comparison of the EHV-1 DNA sequence with that encoding glycoproteins of other alphaherpesviruses has revealed no significant homologies. Comparison at the amino acid level, however, has demonstrated regions of significant sequence similarity between the three complete EHV-1 ORFs 2, 3 and 4, and the herpes simplex virus type 1 (HSV-1) glycoprotein gD encoded by the US6 gene, the HSV-1 glycoprotein gI encoded by the US7 gene and the HSV-1 glycoprotein gE encoded by the US8 gene, respectively. The interrupted ORF 5 was found to display partial homology with the HSV-1 US9-encoded protein, but no homology was found between the protein encoded by ORF 1 and other proteins. The three collinear EHV-1 ORFs encoding putative glycoproteins with homology to the HSV-1 glycoproteins were therefore designated EHV-1 gD, gI and gE, respectively. Moreover, further similarities were found between EHV-1 gD and pseudorabies virus (PRV) gp50, between EHV-1 gI and PRV gp63 and varicellazoster virus (VZV) gpIV, and between EHV-1 gE and PRV gI and VZV gpI. It is concluded that EHV-1, PRV, HSV-1 and VZV encode homologous glycoprotein genes in the small unique components of their genomes and that the genetic organization of these regions is conserved.

Amino Acid Sequence↗
PubMed1999

MosquI, a novel family of mosquito retrotransposons distantly related to the Drosophila I factors, may consist of elements of more than one origin.

A novel family of non-long-terminal-repeat (non-LTR) retrotransposons, named MosquI, was discovered in the yellow fever mosquito, Aedes aegypti. There were approximately 14 copies of MosquI in the A. aegypti genome. Four of the five analyzed MosquI elements were truncated at the 5' ends while one of them, MosquI-Aa2, was full-length. All five MosquI elements ended with 4-10 TAA tandem repeats, as the Drosophila I factors do. Interestingly, MosquI elements were often found near genes and other repetitive elements. The 6,623-bp MosquI-Aa2 contained two open reading frames (ORFs) flanked by a 404-bp 5' untranslated region and a 326-bp 3' untranslated region. The two ORFs code for nucleocapsids, endonuclease, reverse transcriptase, and RNase H domains. Although overall structural and sequence comparisons suggest that MosquI is highly similar to the Drosophila I factors, phylogenetic analysis based on the reverse transcriptase domains of 40 non-LTR retrotransposons indicate that MosquI and I factors are likely paralogous elements which may have been separated before the split between the ancestors of mollusca and arthropoda. Pairwise comparisons between the four truncated MosquI elements showed 96.7%-99.5% identity at the nucleotide level, while comparisons between the full-length MosquI-Aa2 and the truncated copies showed only 80.2%-81.8% identity. These comparisons and preliminary phylogenetic analyses suggest that the full-length and truncated MosquI elements may belong to two subfamilies originating from two source genes that diverged a long time ago. In contrast to the defective I factors in Drosophila melanogaster, which are likely very old components of the genome, the truncated MosquI elements seem to have been recently active. Finally, the genomic distribution and evolution of MosquI elements are analyzed in the context of other non-LTR retrotransposons in A. aegypti.

Aedes↗
PubMed2006

Evolutionary dynamics of prokaryotic transcriptional regulatory networks.

The structure of complex transcriptional regulatory networks has been studied extensively in certain model organisms. However, the evolutionary dynamics of these networks across organisms, which would reveal important principles of adaptive regulatory changes, are poorly understood. We use the known transcriptional regulatory network of Escherichia coli to analyse the conservation patterns of this network across 175 prokaryotic genomes, and predict components of the regulatory networks for these organisms. We observe that transcription factors are typically less conserved than their target genes and evolve independently of them, with different organisms evolving distinct repertoires of transcription factors responding to specific signals. We show that prokaryotic transcriptional regulatory networks have evolved principally through widespread tinkering of transcriptional interactions at the local level by embedding orthologous genes in different types of regulatory motifs. Different transcription factors have emerged independently as dominant regulatory hubs in various organisms, suggesting that they have convergently acquired similar network structures approximating a scale-free topology. We note that organisms with similar lifestyles across a wide phylogenetic range tend to conserve equivalent interactions and network motifs. Thus, organism-specific optimal network designs appear to have evolved due to selection for specific transcription factors and transcriptional interactions, allowing responses to prevalent environmental stimuli. The methods for biological network analysis introduced here can be applied generally to study other networks, and these predictions can be used to guide specific experiments.

Amino Acid Motifs↗
PubMed2005

Genome-wide linkage analysis to urinary microalbuminuria in a community-based sample: the Framingham Heart Study.

INTRODUCTION: Microalbuminuria is a powerful risk factor for cardiovascular disease. It is not known whether genetic factors play a role in the expression of microalbuminuria in population-based samples. METHODS: Genome-wide variance components linkage-analysis using 401 markers spaced at approximately 10 cM was performed on subjects from 330 extended families of the Framingham Heart Study; a subanalysis was performed on families enriched for hypertension. Urinary microalbumin was indexed to urinary creatinine [urine albumin/creatinine ratio (UACR)] and was log-transformed for analysis. Residuals of log-transformed UACR adjusted for age, gender, body mass index, diabetes, systolic blood pressure, hypertension treatment, smoking, and serum creatinine were used in the linkage analysis. RESULTS: Among 1055 subjects (52% women), mean age 56 years, median UACR was 5.8 mg/g (11% >30 mg/g). The unadjusted heritability for UACR was 0.20; after multivariable adjustment, heritability was 0.16. The peak multivariable-adjusted multipoint logarithm of odds (LOD) score was 2.22 on chromosome 8 at 135 cM (marker D8S1179); one LOD support interval = 129 - 145 cM. In the subanalysis in families enriched for hypertension (N= 676), the peak multivariable-adjusted LOD score of 2.11 was observed at the same location. CONCLUSION: We found suggestive linkage to urinary microalbumin on chromosome 8. At least one potential candidate gene implicated in the pathogenesis of nephropathy (HAS2) lies in this region. Further research is warranted to understand the genetic basis of microalbuminuria.

Adult↗
PubMed1996

Genetic conflicts.

Self-promoting elements (also called ultraselfish genes, selfish genes, or selfish genetic elements) are vertically transmitted genetic entities that manipulate their "host" so as to promote their own spread, usually at a cost to other genes within the genome. Examples of such elements include meiotic drive genes and cytoplasmic sex ratio distorters. The spread of a self-promoting element creates the context for the spread of a suppressor acting within the same genome. We may thus say that a genetic conflict exists between different components of the same genome. Here we investigate the properties of such conflicts. First we consider the potential diversity of genomic conflicts and show that every genetic system has potential conflicts. This is followed by analysis of the logic of conflicts. Just as Evolutionarily Stable Strategy (ESS) terminology provides a short cut for discussion of much in behavioral ecology, so the language of modifier analysis provides a useful terminology on which to base discussions of conflicts. After defining genetic conflict, we provide a general analysis of the conflicting parties, and note a distinction between competing and conflicting genes. We then provide a taxonomy of possible short- and long-term outcomes of conflicts, noting that potential conflict in an unconstrained system can never be removed, and that the course of evolution owing to conflict is often unpredictable. The latter is most particularly true for strong conflicts in which suppressors may take surprising forms. The possibility of extended conflicts in the form of "arms races" between element and suppressor is illustrated. The peculiar redundancy of these systems is one possible trace of conflict, and others are discussed. That homologous conflicts may find highly different expression is discussed by referring to the mechanistic differences that are thought to underlie the action of the two best-described meiotic drive genes, and by the multiplicity of forms of cytoplasmic sex ratio distorters. The theoretical analysis establishes a logical basis for thinking about conflicts, but fails to establish the importance of conflict in evolution. We illustrate this contentious issue through consideration of some phenomena for whose evolution conflict has been proposed as an important force: the evolution of sex, sex determination, species, recombination, and uniparental inheritance of cytoplasmic genes. In general, it is proposed that conflict may be a central force in the evolution of genetic systems. We conclude that an analysis of conflict and its general importance in evolution is greatly aided by application of the concept of genetic power. We consider the possible components of genetic power and ask whether and how power evolves.

Animals↗
PubMed1989

Maize streak virus genes essential for systemic spread and symptom development.

The entire genome of single component geminiviruses such as maize streak virus (MSV) consists of a single-stranded circular DNA of ~2.7 kb. Although this size is sufficient to encode only three average sized proteins, the virus is capable of causing severe disease of many monocots with symptoms of chlorosis and stunting. We have identified viral gene functions essential for systemic spread and symptom development during MSV infection. Deletions and gene replacement mutants were created by site-directed mutagenesis and insertion between flanking MSV or reporter gene sequences contained in Agrobacterium T-DNA derived vectors. Following Agrobacterium-mediated inoculation of maize seedlings, the mutated MSV DNAs were excised from these binary vectors by homologous recombination within the flanking sequences. Our analyses show that the capsid gene of MSV, while not required for replication, is essential for systemic spread and subsequent disease development. The ;+' strand open reading frame (ORF) located immediately upstream from the capsid ORF and predicted to encode a 10.9 kd protein was also found to be dispensable for replication but essential for systemic spread. By this analysis, MSV sequences that support autonomous replication were localized to a 1.7 kb segment containing the two viral intergenic regions and two overlapping complementary ;-' strand ORFs. Despite the inability of the gene replacement mutants to spread systemically, both inoculated and newly developed leaves displayed chlorotic patterns similar to the phenotype observed in certain developmental mutants of maize. The similarity of the MSV mutant phenotype to these developmental mutants is discussed.

Journal Article↗
PubMed1995

Strain evolution in Caenorhabditis elegans: transposable elements as markers of interstrain evolutionary history.

Evolutionary relationships across taxa can be deduced from sequence divergence of proteins, RNA, or DNA; sequences which diverge rapidly, such as those of mitochondrial genes, have been especially useful for comparisons of closely related species, and--within limits--of strains within a species. We have utilized the transposable element Tc1 as a polymorphic marker to evaluate the evolutionary relationships among nine Caenorhabditis elegans strains. For five low-Tc1-copy strains, we compared patterns of restriction fragments hybridizing to a cloned Tc1 probe. Twenty of the 40 Tc1 insertion sites thus characterized were common to all five strains, and so presumably preceded strain divergence; the 20 differential bands were used to construct a maximum-parsimony tree relating these strains. In four high-copy-number stocks (three wild-type strains and a subline), we determined occupancy of 35 individual Tc1 insertion sites by a polymerase chain reaction assay. Surprisingly, the high-copy strains share a common subset of these Tc1 insertions, and the chromosomal distribution of conserved Tc1 sites is "clustered" with respect to the other elements tested. These data imply a close evolutionary relationship among the high-copy strains, such that two of these strains appear to have been derived from the highest-copy-number lineage (represented by two stocks) through crossing with a low-Tc1 strain. Abundances of Tc1 elements were also estimated for the four high-copy-number stocks, at approximately 200-500 copies per haploid genome, by quantitative dot-blot hybridization relative to two low-copy strains. Annealing with 32P-labeled probes corresponding to full-length Tc1, an oligonucleotide within the Tc1 terminal inverted repeats, and an internal Tc1 oligonucleotide, gave essentially identical results--indicating that Tc1 termini exist in the genome primarily as components of full-length Tc1 elements. A composite evolutionary tree is proposed, based on the locations and numbers of Tc1 elements in these strains, which is consistent with a four-branch intraspecific tree deduced previously by maximum-parsimony analyses of mitochondrial sequence changes; it also serves to elucidate the evolutionary history of transposon mobility.

Animals↗
PubMed1984

Chromosomal location of a major tRNA gene cluster of Xenopus laevis.

In Xenopus laevis, genes encoding tRNAPhe, tRNATyr, tRNAMet1, tRNAAsn, tRNAAla, tRNALeu, and tRNALys are clustered within a 3.18-kb (kilobase) fragment of DNA. This fragment is tandemly repeated some 150 times in the haploid genome and its components are found outside the repeat only to a limited extent. The fragment hybridizes in situ to a single site very near the telomere on the long arm of one of the acrocentric chromosomes of the group comprising chromosomes 13-18. All the chromosomes of this group also hybridize with DNA coding for oocyte-specific 5S RNA. The tRNA gene cluster is slightly proximal to the cluster of 5S RNA genes.

Animals↗
PubMed1994

I factors in Drosophila melanogaster: transposition under control.

I factors are responsible for the I-R system of hybrid dysgenesis in Drosophila melanogaster. They belong to the LINE class of mobile elements, which transpose via reverse transcription of a full-length RNA intermediate. I factors are active members of the I element family, which also contains defective I elements that are immobilized within peri-centromeric heterochromatin and represent very old components of the genome. Active I factors have recently invaded natural populations of Drosophila melanogaster, giving rise to inducer strains. Reactive strains, devoid of active I factors, derive from old laboratory stocks established before the invasion. Transposition of I factors is activated at very high frequencies in the germline of hybrid females issued from crosses between females from reactive strains and males from inducer strains. It results in the production of high rates of mutations and chromosomal rearrangements as well as in a particular syndrome of sterility. The frequency of transposition of I factors is dependent on the amount of full-length RNA that is synthesized from an internal promoter. This full-length RNA serves both as an intermediate of transposition and presumably as a messenger for protein synthesis. Regulators of transposition apparently affect transcription initiation from the internal promoter. The data presented here lead to the proposal of a tentative model for transposition.

Animals↗
PubMed1987

Molecular aspects of the epidemiology of virus disease.

With regard to molecular epidemiology, influenza A viruses belong to the best-studied virus systems. At least two large reservoirs of influenza A viruses have been built up in nature, one in humans and another one in water fowls. The latter one is very heterogenous, consisting of viruses belonging to 13 hemagglutinin (HA) and 9 neuraminidase (NA) subtypes in almost all possible combinations. The segmented structure of the influenza virus genome allows the creation of new influenza strains by reassortment. By replacement of the HA gene of human strains new pandemic viruses can be generated (antigenic shift). The particular structure of the HA enables the human influenza A-viruses to create variants which can escape the immune response of the host (antigenic drift). The nucleoprotein is responsible for keeping those two large reservoirs apart. Mixing of genes of viruses from these two reservoirs seems to happen predominantly by double infection of pigs, which apparently are tolerant for infection by either human or avian influenza viruses. The molecular mechanisms described for influenza viruses can be explained by the particular structure of their genome and their components and cannot be generalized. Each virus has developed its own strategy to multiply and to spread.

Animals↗
PubMed1995

Breast Cancer: A Revolutionary Concept.

In this paper we trace the evolution of paradigms concerning the nature of breast cancer and their therapeutic consequences. There is no doubt that the conceptual revolution of about 20 years ago has led to modest gains in survival following the use of adjuvant systemic therapy and the quality of survival by demonstrating the safety of conservative surgical regimens. At the same time, there seems to be a plateau in progress. The results of adjuvant systemic therapy are not as good as anticipated and there are a number of other inconsistencies within the conventional model of biological predeterminism that remain to be explained. We offer up an alternative paradigm that suggests that not all metastases are due to cellular dissemination with late onset local and distant recurrence resulting from a transfection phenomenon, whereby subcellular particles shed by the primary cancer cell are taken up by wandering cells of the monocyte macrophage system and transported to distant sites where the local mesenchymal cells are transfected with the genetic information that activates components of the genome to instruct these plastic cells to express the phenotypic picture of a dedifferentiated breast duct epithelial cell. Such a conceptual revolution will open up the way for a new program of research and the development of therapies based on anti-viral rather than cytotoxic drugs.

Journal Article↗
PubMed1999

The role of interelement selection in Saccharomyces cerevisiae Ty element evolution.

Retrotransposons are mobile genetic elements that are ubiquitous components of eukaryotic genomes. The evolutionary success of retrotransposons is explained by their ability to replicate faster than the host genomes in which they reside. Elements with higher rates of genomic replication possess a selective advantage over less active elements. Retrotransposon populations, therefore, are shaped largely by selective forces acting at the genomic level between elements. To evaluate rigorously the effects of selective forces acting on retrotransposons, detailed information on the patterns of molecular variation within and between retrotransposon families is needed. The sequencing of the Saccharomyces cerevisiae genome, which includes the entire genomic complement of yeast retrotransposons, provides an unprecedented opportunity to access and analyze such data. In this study, we analyzed in detail the patterns of nucleotide variation within the open reading frames of two parental (Ty1 and Ty2) and one hybrid (Ty1/2) family of yeast retrotransposons. The pattern and distribution of nucleotide changes on the phylogenetic reconstructions of the three families of Ty elements reveal evidence of negative selection on both internal and external branches of the Ty phylogenies. These results indicate that most, if not all, Ty elements examined represent active or recently active retrotransposon lineages. We discuss the relevance of these findings with respect to the coevolutionary dynamic operating between genomic element populations and the host organisms in which they reside.

Databases, Factual↗
PubMed2002

Electrophoretic karyotyping and gene mapping of seven formae speciales in Fusarium solani.

Chromosomal DNAs of 22 strains in 7 formae speciales (f. spp.) of Fusarium solani were compared by pulsed field gel electrophoresis (PFGE) and gene mapping on the chromosomes. Using PFGE, complete separation of the full components of the genome was not attained, due to the limited resolution of large chromosomes, but 5-12 chromosomes with sizes of 0.6-5.7 Mbp were resolvable for every strain. Although each strain had a unique banding profile, similarity in the banding profile was noticed among strains of the same (f. sp.). In gene mapping, the ribosomal RNA gene (rDNA) and putative pathogenesis-related genes encoding kievitone hydratase (khs), pisatin demethylase (pda) and pectate-degrading enzyme (pelA) were located on the chromosomes separated by PFGE. rDNA was always detected on the stacked large bands of 5.2-5.7 Mbp. The khs gene was detected on a chromosome of 2.8-5.4 Mbp in all f. sp. phaseoli strains and one strain of f. sp. pisi. The pda gene was detected on a chromosome of 1.4-5.6 Mbp in f. sp. pisi and pelA was localized on a chromosome of 2.3-2.9 Mbp in f. spp. pisi, xanthoxyli, batatas and mori. The results of PFGE and Southern blot hybridization supported the idea that each f. sp. of F. solani (or mating population of the teleomorph Nectria haematococca) has a distinctive genomic organization, as previously inferred from molecular phylogenetic analyses.

Chromosome Mapping↗
PubMed2006

Epigenetic regulation of the rice retrotransposon Tos17.

Transposable elements are major components of plant genomes. Their activity seems to be epigenetically regulated by gene silencing systems. Here we report epigenetic variation in the retrotransposon Tos17 activity in rice varieties. Of the two copies of Tos17 present in chromosome 7 (Tos17 (chr.7)) and chromosome 10 (Tos17 (chr.10)), Tos17 (chr.7) is strongly activated by tissue culture in most varieties including Nipponbare except for Moritawase, despite the identity of the DNA sequences in Moritawase and Nipponbare. Tos17 (chr.7) activity correlated with its methylation status, and Tos17 (chr.7 )in Moritawase was heavily methylated and activated by treatment of 5-azacytidine (5-azaC), a DNA methylation inhibitor. Although the original copies of Tos17 are methylated to some extent in all varieties examined, the transposed copies in calli mostly are not methylated. When plants were regenerated from calli, the degree of methylation of the Tos17 DNA increased gradually with the growth of plants, and a significant progress of DNA methylation occurred in the next generation after a completed reproductive cycle. With increasing DNA methylation, the transcription of transposed and original Tos17 copies driven by its own as well as by a flanking gene promoter were suppressed. We conclude that Tos17 DNA methylation controls the transpositional activity of Tos17, and modulates the activity of neighboring genes. Based on the analysis of the inactive Tos17 (chr.10), we propose that another mechanism, called transcriptional interference, is involved in the control of Tos17 activity.

Base Sequence↗
PubMed2005

Advent of a new retrotransposon structure: the long form of the Veju elements.

Transposable elements are the main component of plant genomes, especially in grass species. In a previous analysis, we have identified two unusual types of Class I elements, two homologous Veju TRIM elements, but with an unusual long structure. They are formed by the junction of a yet unidentified segment labelled unknown DNA, flanked by the borders of the classical Veju element. Here, we show that the long (Veju_L) and the short forms (Veju_S) coexist within wheat genomes. The associated unknown DNA had always the same origin, and the Veju_L came probably from either illegitimate recombinations or 'template switching' between the Veju_S and another unique unknown DNA sequence. This junction then evolved differently within wheat genomes.

Base Sequence↗