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We designed a web-based program, Tree View (TV), which uses a dynamic data structure algorithm to draw the phylogenetic tree for a family of homologous proteins. This program has a user-friendly interface and can be easily implemented into other programs for convenient protein sequence analysis. It is available at our web site: http://www.biology.ucsd.edu-yzhai/biotools.html.
Ferritin, a protein widespread in nature, concentrates iron approximately 10(11)-10(12)-fold above the solubility within a spherical shell of 24 subunits; it derives in plants and animals from a common ancestor (based on sequence) but displays a cytoplasmic location in animals compared to the plastid in contemporary plants. Ferritin gene regulation in plants and animals is altered by development, hormones, and excess iron; iron signals target DNA in plants but mRNA in animals. Evolution has thus conserved the two end points of ferritin gene expression, the physiological signals and the protein structure, while allowing some divergence of the genetic mechanisms. Comparison of ferritin gene organization in plants and animals, made possible by the cloning of a dicot (soybean) ferritin gene presented here and the recent cloning of two monocot (maize) ferritin genes, shows evolutionary divergence in ferritin gene organization between plants and animals but conservation among plants or among animals; divergence in the genetic mechanism for iron regulation is reflected by the absence in all three plant genes of the IRE, a highly conserved, noncoding sequence in vertebrate animal ferritin mRNA. In plant ferritin genes, the number of introns (n = 7) is higher than in animals (n = 3). Second, no intron positions are conserved when ferritin genes of plants and animals are compared, although all ferritin gene introns are in the coding region; within kingdoms, the intron positions in ferritin genes are conserved. Finally, secondary protein structure has no apparent relationship to intron/exon boundaries in plant ferritin genes, whereas in animal ferritin genes the correspondence is high. The structural differences in introns/exons among phylogenetically related ferritin coding sequences and the high conservation of the gene structure within plant or animal kingdoms of the gene structure within plant or animal kingdoms suggest that kingdom-specific functional constraints may exist to maintain a particular intron/exon pattern within ferritin genes. In the case of plants, where ferritin gene intron placement is unrelated to triplet codons or protein structure, and where ferritin is targeted to the plastid, the selection pressure on gene organization may relate to RNA function and plastid/nuclear signaling.
BACKGROUND: The 5'-terminal cap structure plays an important role in many aspects of mRNA metabolism. Capping enzymes encoded by viruses and pathogenic fungi are attractive targets for specific inhibitors. There is a large body of experimental data on viral and cellular methyltransferases (MTases) that carry out guanine-N7 (cap 0) methylation, including results of extensive mutagenesis. However, a crystal structure is not available and cap 0 MTases are too diverged from other MTases of known structure to allow straightforward homology-based interpretation of these data. RESULTS: We report a 3D model of cap 0 MTase, developed using sequence-to-structure threading and comparative modeling based on coordinates of the glycine N-methyltransferase. Analysis of the predicted structural features in the phylogenetic context of the cap 0 MTase family allows us to rationalize most of the experimental data available and to propose potential binding sites. We identified a case of correlated mutations in the cofactor-binding site of viral MTases that may be important for the rational drug design. Furthermore, database searches and phylogenetic analysis revealed a novel subfamily of hypothetical MTases from plants, distinct from "orthodox" cap 0 MTases. CONCLUSIONS: Computational methods were used to infer the evolutionary relationships and predict the structure of Eukaryotic cap MTase. Identification of novel cap MTase homologs suggests candidates for cloning and biochemical characterization, while the structural model will be useful in designing new experiments to better understand the molecular function of cap MTases.
The main methodology employed in the progressive gross anatomy of today's Japan is typological anatomy (typologische Anatomie) as introduced by Seiho Nishi (1943; 1950; 1961). This typological methodology is sufficient to suggest the existence of a certain constancy between muscle phylogeny and innervation in spite of the classic theory of nerve-muscle specificity having been discredited. On the basis of findings obtained from the many recent Japanese studies including the author's study on the cervical plexus (Kida, 1987), it has been noted that the stratum-structure of the spinal nerves may be an important key for the phylogenetic understanding of animal body structure (Kida, 1988). 1) The stratum-structure of the spinal nerves was initially observed only in the limb plexus by Fürbringer (Schwalbe, 1981). At that time, it was accepted as the longitudinal strata corresponding to the portion occupied by nerve fibers to the flexors or the extensors (Bolk, 1902). This theory was effective for the systematic understanding of limb structure. 2) The stratum-structure of the spinal nerves was at first considered to be related to the concept of nerve-muscle specificity. After the review of Straus (1946) on the concept of nerve-muscle specificity, this concept was disproved and has since been generally regarded as a theory of the past, therefore stratum-structure is now treated independently of that concept. 3) However, recent Japanese studies have modified and progressed beyond the concept of the stratum-structure of the spinal nerves.(ABSTRACT TRUNCATED AT 250 WORDS)
In this paper we are submitting studies on the onto- and phylogenetic development of the superficial muscular and fascial layers of the hand and forearm of mammals. The object of this study was to investigate the following items: the ontogenetic development of the m. flexor digitorum superficialis, of the m. flexor digitorum profundus, of the m. palmaris longus, of the palmaris brevis of the human hand, the nerve supply of these muscles, the development of palmar and plantar aponeurosis and of other fasciae related to the palmar and plantar aponeuroses. We compared conclusions drawn from the studies on the ontogenetic development with observations gained from the phylogenetic development of the structures of the human hand and forearm and applied our findings to various species of mammals. The results of these comparisons are expressed in this study presenting interpretations of the phylogenetic development of superficial muscular and fascial layers of the mammalian hand and foot. Furthermore we ascertained the homology of the superficial muscular and fascial layer of the mammalian autopodion, we reviewed one of the theories on the origin of Dupuytren's contracture and commented on opinions of the developmental origin of certain muscular varieties present in the human hand and forearm. Apart from this we established certain basic data on the development of the fasciae of the human hand and foot. Our findings on the variability of the palmar aponeurotic attachments of the human hand were confronted with the incidence and frequency of one particular finger when affected by a Dupuytren's contracture and we commented on the predisposition of certain fingers or toes for the affliction of this impairment. We conducted 152 series of histological sections through the hand and feet of embryos and foetuses sized 12-100 mm in c.-r. length, as well as 84 series of histological transverse sections through human embryonal hands in order to study the ontogenetic development of superficial muscular and fascial layers of the human hand, forearm and foot. The embryonal extremities were cut transversally, parallel to the palm and several sagittal sections were carried out for control purposes. The phylogenetic development of the superficial muscular and fascial layers of the hand was investigated by specimens processed under a micro-dissecting microscope. 55 specimens of various extremities were thus prepared, obtained from 22 species of mammals. Many animals were selected in order to cover species of mammals significant for their evolution.(ABSTRACT TRUNCATED AT 400 WORDS)
BACKGROUND: To infer the tree of life requires knowledge of the common characteristics of each species descended from a common ancestor as the measuring criteria and a method to calculate the distance between the resulting values of each measure. Conventional phylogenetic analysis based on genomic sequences provides information about the genetic relationships between different organisms. In contrast, comparative analysis of metabolic pathways in different organisms can yield insights into their functional relationships under different physiological conditions. However, evaluating the similarities or differences between metabolic networks is a computationally challenging problem, and systematic methods of doing this are desirable. Here we introduce a graph-kernel method for computing the similarity between metabolic networks in polynomial time, and use it to profile metabolic pathways and to construct phylogenetic trees. RESULTS: To compare the structures of metabolic networks in organisms, we adopted the exponential graph kernel, which is a kernel-based approach with a labeled graph that includes a label matrix and an adjacency matrix. To construct the phylogenetic trees, we used an unweighted pair-group method with arithmetic mean, i.e., a hierarchical clustering algorithm. We applied the kernel-based network profiling method in a comparative analysis of nine carbohydrate metabolic networks from 81 biological species encompassing Archaea, Eukaryota, and Eubacteria. The resulting phylogenetic hierarchies generally support the tripartite scheme of three domains rather than the two domains of prokaryotes and eukaryotes. CONCLUSION: By combining the kernel machines with metabolic information, the method infers the context of biosphere development that covers physiological events required for adaptation by genetic reconstruction. The results show that one may obtain a global view of the tree of life by comparing the metabolic pathway structures using meta-level information rather than sequence information. This method may yield further information about biological evolution, such as the history of horizontal transfer of each gene, by studying the detailed structure of the phylogenetic tree constructed by the kernel-based method.
In S. cerevisiae, ribosomal protein L32 regulates the splicing of the transcript of its own gene, RPL32. We have identified an RNA structure within the transcript that is responsible for this regulation. Initial deletions limited essential sequences to the 5' exon and the first few nucleotides of the intron. To take advantage of phylogenetic comparison of RNA structures, RPL32 was cloned from the closely related species, Kluyveromyces lactis. The splicing of its transcript is similarly regulated. Sequences conserved between the S. cerevisiae and K. lactis transcripts suggested a structure involving base pairing of a region encompassing the 5' splice site with another near the 5' end of the transcript. Analysis of numerous site-directed mutations supports this structure. We infer that stabilization of this structure by L32 inhibits splicing by precluding the interaction of U1 RNA with the 5' splice site.
ADP-ribosylation factor 4 (ARF4) is a member of a family of approximately 20 kDa guanine nucleotide-binding proteins that were initially identified by their ability to stimulate the ADP-ribosyltransferase activity of cholera toxin in vitro. They have recently been shown to play a role in vesicular trafficking and as activators of phospholipase D. The organization of the human ARF4 gene was determined from a genomic clone isolated from an arrayed PAC genomic library. The gene spans approximately 12 kb and contains six exons and five introns. Translation initiates in exon 1 and terminates in exon 6. Nuclease protection experiments indicated that the major transcription initiation site is located 211 bp 5' to the start of translation. In some cell lines derived from human tissues, however, multiple initiation sites were observed. The proximal 5'-flanking region of the human ARF4 gene lacks a TATA box, is highly GC rich, and contains multiple potential Spl-binding sites. An alignment of the exons for the class I ARF genes (ARF1, ARF2, and ARF3) and class II ARF genes (ARF4 and ARF5) reveals that the members of each class share a common gene organization. The structures of the class I and II ARF genes, however, are quite distinct and support the division of the ARFs into these groups based on deduced amino acid sequence, protein size, phylogenetic analysis, and gene structure.
There is a long-standing debate over whether or not the Pleistocene glaciations promoted speciation. While some models predict that extensive mixing of populations during interglacial expansion would have inhibited divergence, others postulate that divergence among allopatric glacial refuges or founder events during recolonization of previously glaciated areas would have promoted differentiation. Using a combination of traditional and coalescent based population genetic approaches, this study finds that the glaciations did not inhibit divergence among populations of the grasshopper Melanoplus oregonensis. Instead, drift associated with recolonization of previously glaciated areas, as well as divergence among multiple allopatric glacial refugia, have both contributed to differentiation in this montane grasshopper from the 'sky islands' of the northern Rocky Mountains. Significant population structure was detected by phylogenetic and FST analyses, including significant FST values among individual pairs of sky-island populations. In addition to clustering of haplotypes within populations, there is some evidence of regional phylogeographic structure, although none of the 'regional groups' form a monophyletic clade and there is a lack of concordance between the genealogical and geographical positions of some haplotypes. However, coalescent simulations confirm there is significant regional phylogeographic structure that most likely reflects divergence among multiple ancestral refugial populations, and indicate that it is very unlikely that the observed gene tree could have been produced by the fragmentation of a single widespread ancestral population. Thus, rather than inhibiting differentiation, the glaciations appear to have promoted population divergence in M. oregonensis, suggesting that they may have contributed to the radiation of Melanoplus species during the Pleistocene.
A wide range of RNA viruses use programmed -1 ribosomal frameshifting for the production of viral fusion proteins. Inspection of the overlap regions between ORF1a and ORF1b of the SARS-CoV genome revealed that, similar to all coronaviruses, a programmed -1 ribosomal frameshift could be used by the virus to produce a fusion protein. Computational analyses of the frameshift signal predicted the presence of an mRNA pseudoknot containing three double-stranded RNA stem structures rather than two. Phylogenetic analyses showed the conservation of potential three-stemmed pseudoknots in the frameshift signals of all other coronaviruses in the GenBank database. Though the presence of the three-stemmed structure is supported by nuclease mapping and two-dimensional nuclear magnetic resonance studies, our findings suggest that interactions between the stem structures may result in local distortions in the A-form RNA. These distortions are particularly evident in the vicinity of predicted A-bulges in stems 2 and 3. In vitro and in vivo frameshifting assays showed that the SARS-CoV frameshift signal is functionally similar to other viral frameshift signals: it promotes efficient frameshifting in all of the standard assay systems, and it is sensitive to a drug and a genetic mutation that are known to affect frameshifting efficiency of a yeast virus. Mutagenesis studies reveal that both the specific sequences and structures of stems 2 and 3 are important for efficient frameshifting. We have identified a new RNA structural motif that is capable of promoting efficient programmed ribosomal frameshifting. The high degree of conservation of three-stemmed mRNA pseudoknot structures among the coronaviruses suggests that this presents a novel target for antiviral therapeutics.
Structural similarities between proteins with no amino acid sequence homology either indicate a phylogenetic relationship, or they are merely the expression of a physically preferred way of folding a polypeptide chain. It is shown that one can distinguish between these alternatives by evaluating the "significance of the similarity". Such significances have been derived for comparison between chain folds containing beta-pleated sheets (Schulz and Schirmer, 1974; Richardson et al., 1976; Sternberg and Thornton, 1976). An extension of this method to comparisons between any two chain folds is outlined here.
The recent structure determination of the phylogenetically conserved cor re of the signal recognition particle (SRP) reveals a novel of highly un usual RNA-protein interface, where non-canonical base pairs play a centr al role. The structure shows how a helix-turn-helix motif can be employ ed to bind RNA and offers hints as to how the signal peptide is recogniz ed by the SRP.
Vertebrate U17 RNA is an intron-encoded H/CA box containing snoRNA, which has been intensively studied in the last decade, though its precise role in ribosome biogenesis is not yet clear. A consensus secondary structure for the U17 RNA molecule has been derived from the comparative sequence and structural evolution analysis of U17 snoRNA among vertebrates. Its phylogenetic congruence above class level has been tested and preliminary data on chelonians suggest that also in this order, U17 snoRNA evolved congruently with phylogeny. We herein extend our analysis to other components of this reptile group. According to the sequence data that have also emerged from chelonians, the U17 RNA molecule can be divided into two main domains: the 5'-variable domain, which presents the sequence motifs capable of base-pairing with the 18S rRNA target and spanning STEM1, -2, and -3, and the 3'-conserved domain, consisting of STEM4. In vertebrates, the latter RNA region shows a high conservation both in secondary structure and in the presence of the three sequence motifs 5'-AUUCCUA-3', 5'-U(G/U)ACU-3', and 5'-AACCC-3'. We tested the phylogenetic congruence of U17 evolution with chelonian relationships: Our results are significantly similar to those emerging from mtDNA and morphological systematics. Some discrepancies (e.g., the position of Platysternon) need to be addressed in greater depth.
A collection of 2,209 isolates of six polysaccharide capsule types of Haemophilus influenzae, including 1,975 serotype b isolates recovered in 30 countries was characterized for electrophoretically demonstrable allele profiles at 17 metabolic enzyme loci. Two hundred eighty distinct multilocus genotypes were distinguished, and cluster analysis revealed two primary phylogenetic divisions. The population structure of encapsulated H. influenzae is clonal. Currently, most of the invasive disease worldwide is caused by serotype b strains of nine clones. Strains producing serotype c, e, and f capsules belong to single divisions and have no close genetic relationships to strains of other serotypes. Serotype a and b strains occur in both primary phylogenetic divisions, probably as a result of transfer and recombination of serotype-specific sequences of the cap region between clonal lineages. A close genetic relatedness between serotype d isolates and some strains of serotypes a and b was identified. There are strong patterns of geographic variation, on an intercontinental scale, in both the extent of genetic diversity and the clonal composition of populations of encapsulated strains. The analysis suggests that the present distribution of clones is, in part, related to patterns of racial or ethnic differentiation and historical demographic movements of the human host populations.
Eucaryotic pre-rRNA spacers are evolutionarily highly variable in sequence and size, and are markedly expanded in vertebrates, particularly in mammals. The longest mammalian spacer by far is the 3.5-4-kb 5' external transcribed spacer (5'-ETS), which is excised in two steps. We present a folding model for the entire mammalian 5'-ETS, derived from comparative analyses and thermodynamic predictions for mouse, rat and human sequences, which should prove helpful in identifying cis-acting processing signals, particularly those involved in its early internal cleavage, for which U3 RNA is an essential factor. Although the rodent and primate sequences have extensively diverged, a series of relatively conserved sequence tracts can nevertheless be identified: they participate in base-pairing, preserved through the occurrence of compensatory base changes, which delineate four independent domains of secondary structure. The first domain is located entirely upstream from the site of internal cleavage. The second domain, immediately downstream from this cleavage site, encompasses most of the region required for faithful and efficient in vitro processing at this site. Phylogenetically supported conserved structures also define two other independent domains, encompassing most of the 5'-ETS length, with the presence of giant hairpins (extending from the conserved core elements) which exhibit both some analogous features and substantial differences between man and mouse. The comparative analysis was extended to the two other vertebrate sequences available so far, amphibians Xenopus laevis and Xenopus borealis. The amphibian folding model, supported by comparative evidence between these two species, displays some features in common with the mammalian model, with a similar organization into four separate domains of secondary structure, suggesting the functional relevance of these structures in the process of ribosome formation.
BACKGROUND: In a previous report (La et al., Proteins, 2005), we have demonstrated that the identification of phylogenetic motifs, protein sequence fragments conserving the overall familial phylogeny, represent a promising approach for sequence/function annotation. Across a structurally and functionally heterogeneous dataset, phylogenetic motifs have been demonstrated to correspond to a wide variety of functional site archetypes, including those defined by surface loops, active site clefts, and less exposed regions. However, in our original demonstration of the technique, phylogenetic motif identification is dependent upon a manually determined similarity threshold, prohibiting large-scale application of the technique. RESULTS: In this report, we present an algorithmic approach that determines thresholds without human subjectivity. The approach relies on significant raw data preprocessing to improve signal detection. Subsequently, Partition Around Medoids Clustering (PAMC) of the similarity scores assesses sequence fragments where functional annotation remains in question. The accuracy of the approach is confirmed through comparisons to our previous (manual) results and structural analyses. Triosephosphate isomerase and arginyl-tRNA synthetase are discussed as exemplar cases. A quantitative functional site prediction assessment algorithm indicates that the phylogenetic motif predictions, which require sequence information only, are nearly as good as those from evolutionary trace methods that do incorporate structure. CONCLUSION: The automated threshold detection algorithm has been incorporated into MINER, our web-based phylogenetic motif identification server. MINER is freely available on the web at http://www.pmap.csupomona.edu/MINER/. Pre-calculated functional site predictions of the COG database and an implementation of the threshold detection algorithm, in the R statistical language, can also be accessed at the website.
Male insects that are attracted by sex pheromones to find their female mates over long distances have specialized olfactory subsystems. Morphologically, these subsystems are characterized by a large number of receptor neurons sensitive to components of the female's pheromones and hypertrophied glomerular subunits ('macroglomeruli' or 'macroglomerular complexes') in the antennal lobes, in which the axons of the receptor neurons converge. The olfactory subsystems are adapted for an increased sensitivity to perceive minute amounts of pheromones. In Apis mellifera, drones have 18,600 olfactory poreplate sensilla per antenna, each equipped with receptor neurons sensitive to the queen's sex pheromone, and four voluminous macroglomeruli (MG1-MG4) in the antennal lobes. In contrast, we show that drones of the phylogenetically distant species, Apis florea, have only 1,200 poreplate sensilla per antenna and only two macroglomeruli in their antennal lobes. These macroglomeruli are homologous in anatomical position to the two most prominent macroglomeruli in A. mellifera, the MG1 and MG2, but they are much smaller in size. The morphological and anatomical differences described here suggest major modifications in the sex-pheromone processing subsystem of both species: (1) less pheromone sensitivity in A. florea and (2) a more complex sex-pheromone processing and thus a more complex sex-pheromone communication in A. mellifera. Research in honey bee sex-pheromone communication dates back to the 1960s, when Gary (1962) demonstrated that in Apis mellifera the queen's mandibular gland secretion and especially its main component, 9-ODA (9-keto-2(E)-decenoic acid), is highly attractive to drones on their nuptial flight. Later, cross-species attraction experiments showed that other honey bee species, Apis florea, A. cerana, and A. dorsata probably also use the queen's mandibular gland secretion as a mating attractant (Butler et al. 1967; Sanasi et al. 1971). Besides its function in mating behavior, the queen's mandibular gland secretion is the main pheromone regulating queen-worker interactions (Free 1987). In this context, several studies have demonstrated the behavioral significance of single components (Slessor et al. 1988) and differences in the composition of the secretion between Apis species (Plettner et al. 1996, 1997; Keeling et al. 2000). Regarding the interspecific differences in the queen's signal, the question arises whether this variation is reflected in the olfactory system of drones and workers of the various species.
A collection of diverse 16S and 16S-like rRNA secondary structure diagrams are available. This set of rRNAs contains representative structures from all of the major phylogenetic groupings--Archaea, (eu)Bacteria, and the nucleus, mitochondrion, and chloroplast of Eucarya. Within this broad phylogenetic sampling are examples of the major forms of structural diversity currently known for this class of rRNAs. These structure diagrams are available online through our computer-network WWW server and anonymous ftp, as well as from the author in hardcopy format.