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PubMed2004

Evolutionary convergence of alternative splicing in ion channels.

In Drosophila melanogaster and humans, members of three different ion-channel gene families share tandem exon duplications, which are alternatively spliced. In this article, I demonstrate that the duplication events that give rise to these mutually exclusive exons are unlikely to be ancestral but have probably occurred independently in different lineages. These events provide remarkable examples of evolutionary convergence in alternative splicing. The result has important implications for the analysis of regulation of alternative splicing using comparative genomics and our understanding of molecular evolution.

Alternative Splicing↗

PubMed2004

Unexpected conserved non-coding DNA blocks in mammals.

The significance of non-coding DNA is a longstanding riddle in the study of molecular evolution. Using a comparative genomics approach, Dermitzakis and colleagues have recently shown that at least some non-coding sequence, frequently ignored as meaningless noise, might bear the signature of natural selection. If functional, it could mark a turning point in the way we think about the evolution of the genome.

Animals↗

PubMed2004

Tarantulas: eight-legged pharmacists and combinatorial chemists.

Tarantula venoms represent a cornucopia of novel ligands for a variety of cell receptors and ion channels. The diversity of peptide toxin pharmacology has been barely explored as indicated by pharmacological, toxicological and mass spectrometry investigations on more than 55 tarantula venoms. MALDI-TOF MS analysis reveals that the pharmacological diversity is based on relatively small size peptides, which seem to fall into a limited number of structural patterns. Properties and biological activities of the 33 known peptide toxins from tarantula venoms are described. Most known toxins conform to the Inhibitory Cystine Knot (ICK) motif, with differences in the length of intercysteine loops. Recently described peptides show that tarantula toxins can fold according to an elaboration of the Disulfide-Directed beta-Hairpin (DDH) motif which is also the canonical motif for the ICK fold. The ICK fold itself offers many variations leading to differing toxin properties. Examination of pharmacological data gives insights on the possible conserved site of action of toxins acting on voltage-gated ion channels and other toxins acting by a pore-blocking mechanism. Structure-activity data shows the versatility of the toxin scaffolds and the importance of surface features in the selectivity and specificity of these toxins. Tarantulas appear to be a good model for the discovery of novel compounds with important therapeutic potential, and for the study of the molecular evolution of peptide toxins.

Amino Acid Motifs↗

PubMed2005

Hepatitis B virus genotypes.

Eight genotypes of hepatitis B virus (A-H) are currently recognized, and subgenotypes have recently been described in four of these genotypes (A, B, C and F). The genotypes show a distinct geographical distribution between and even within regions, and are proving to be an invaluable tool in tracing the molecular evolution and patterns and modes of spread of hepatitis B virus. Structural and functional differences between genotypes can influence the severity, course and likelihood of complications, and response to treatment of hepatitis B virus infection and possibly vaccination against the virus. Although the number of studies on these genotypes has increased dramatically during recent years, much remains to be learnt about their full implications.

Animals↗

PubMed2006

Molecular characterization of recent Korean porcine reproductive and respiratory syndrome (PRRS) viruses and comparison to other Asian PRRS viruses.

Twenty-eight PRRS viruses (PRRSVs) isolated from various pig farms in Korea between 2002 and 2003 were sequenced for open-reading frame (ORF) 5 and/or full-length genome and compared with numerous PRRSVs reported from North America, Europe and Asia. All Korean isolates examined were genetically of the North American genotype. The ORF5 sequence of one isolate was identical to Ingelvac PRRS MLV vaccine virus. ORF5 nucleotide sequence divergence of the remaining 27 Korean PRRSVs from VR-2332, the prototype of the North American PRRSV and parental strain of the MLV vaccine virus, ranged from 1.3% to 12.9%, which corresponded to 2.0% to 14.9% divergence at the amino acid level, raising a concern on the efficacy of the MLV vaccine. Phylogenetic analyses of ORF5 and/or full-length sequences revealed that the Korean PRRSVs formed a clade distinct from PRRSVs reported from other Asian countries (China, Taiwan, Japan, and Thailand). Our study demonstrated that PRRSVs of the North American genotype were introduced to the Korean swine population some time ago and have evolved independently from PRRSV in other Asian countries, suggesting that geographic separation might influence the molecular evolution of PRRSV. This should be taken into consideration when a national PRRS prevention and control policy for international trade is established.

Amino Acid Sequence↗

PubMed2006

Influenza B viruses isolated in Uruguay during the 2002-2005 seasons: genetic relations and vaccine strain match.

Monitoring antigenic and genetic variations of circulating influenza viruses is critical for the selection of annual vaccine strains. In order to gain insight into the molecular evolution of Influenza B viruses (IBV) isolated in Uruguay in 2002 and 2005 outbreaks, antigenic and phylogenetic studies were carried out for the Hemagglutinin (HA) gene. Antigenic relations among Uruguayan and reference strains isolated elsewhere were performed by means of hemagglutination inhibition assays (HAI). Genetic relations of HA genes from Uruguayan as well as 41 IBV strains isolated elsewhere were established by means of the construction of phylogenetic trees. HAI assays showed a distant antigenic relationship among the 2002 Uruguayan isolates and the 2002 vaccine strain B/Sichuan/379/99. Phylogenetic analysis also revealed a distant genetic relationship among Uruguayan and 2002 vaccine strains. All 2005 IBV Uruguayan strains were both antigenically and genetically related to B/Victoria lineage-viruses. The results of these studies revealed that 2002 IBV Uruguayan strains have a distant antigenic and genetic relation with the 2002 IBV vaccine strain used in Uruguay. The high rate of susceptible individuals in the youngest cohort (<25 years) might be related to the fact that the B/Victoria lineage-viruses were not previously circulating in Uruguay.

Disease Outbreaks↗

PubMed2004

Assessing the passerine "Tapestry": phylogenetic relationships of the Muscicapoidea inferred from nuclear DNA sequences.

This study presents new comparative sequence data from the nuclear RAG-1 gene for an increased taxon sample in order to investigate phylogenetic relationships among a diverse songbird superfamily, the Muscicapoidea, which has variously included the waxwings, silky flycatchers, Palm Chat, dippers, starlings, mockingbirds, thrushes, chats, and Old World flycatchers. At the same time, our results provide a test of the often-cited relationships inferred from the phenetic studies of Sibley and Ahlquist [Phylogeny and Classification of Birds: A Study in Molecular Evolution. Yale University Press, New Haven, 1990] using DNA hybridization distances. Nuclear DNA sequences confirm the monophyly of the "core muscicapoid" group, as defined by Barker et al. [Proc. R. Soc. Lond. B 269 (2002) 295] and also support the sister-group relationship of the Sturnidae and Mimidae, on the one hand, and the large-bodied thrushes (Turdini)+the Old World flycatchers and robins, on the other. The results of the phylogenetic analysis allow preliminary inferences about muscicapoid biogeographic history.

Animals↗

PubMed2004

A comparison of methods for estimating the transition:transversion ratio from DNA sequences.

Estimation of the ratio of the rates of transitions to transversions (TI:TV ratio) for a collection of aligned nucleotide sequences is important because it provides insight into the process of molecular evolution and because such estimates may be used to further model the evolutionary process for the sequences under consideration. In this paper, we compare several methods for estimating the TI:TV ratio, including the pairwise method [TREE 11 (1996) 158], a modification of the pairwise method due to Ina [J. Mol. Evol. 46 (1998) 521], a method based on parsimony (TREE 11 (1996) 158), a method due to Purvis and Bromham [J. Mol. Evol. 44 (1997) 112] that uses phylogenetically independent pairs of sequences, the maximum likelihood method, and a Bayesian method [Bioinformatics 17 (2001) 754]. We examine the performance of each estimator under several conditions using both simulated and real data.

Animals↗

PubMed2005

The position of the Hymenoptera within the Holometabola as inferred from the mitochondrial genome of Perga condei (Hymenoptera: Symphyta: Pergidae).

We sequenced most of the mitochondrial genome of the sawfly Perga condei (Insecta: Hymenoptera: Symphyta: Pergidae) and tested different models of phylogenetic reconstruction in order to resolve the position of the Hymenoptera within the Holometabola, using mitochondrial genomes. The mitochondrial genome sequenced for P. condei had less compositional bias and slower rates of molecular evolution than the honeybee, as well as a less rearranged genome organization. Phylogenetic analyses showed that, when using mitochondrial genomes, both adequate taxon sampling and more realistic models of analysis are necessary to resolve relationships among insect orders. Both parsimony and Bayesian analyses performed better when nucleotide instead of amino acid sequences were used. In particular, this study supports the placement of the Hymenoptera as sister group to the Mecopterida.

Amino Acid Sequence↗

PubMed2000

Peroxidases.

The family of human peroxidases described includes myeloperoxidase, eosinophil peroxidase, uterine peroxidase, lactoperoxidase, salivary peroxidase, thyroid peroxidase and prostaglandin H1/2 synthases. The chemical identity of the peroxidase compound I and II oxidation states for the different peroxidases are compared. The identities of the distal and proximal amino acids of the catalytic site of each peroxidase are also compared. The gene characteristics and chromosomal location of the human peroxidase family have been tabulated and their molecular evolution discussed. Myeloperoxidase polymorphism and the mutations identified so far that affect myeloperoxidase activity and modulate their susceptibility to disease is described. The mechanisms for hypohalous and hypothiocyanate formation by the various peroxidases have been compared. The cellular function of the peroxidases and their hypohalites have been described as well as their inflammatory effects. The peroxidase catalysed cooxidation of drugs and xenobiotics that results in oxygen activation by redox cycling has been included. Low-density lipoprotein oxidation (initiation of atherosclerosis), chemical carcinogenesis, idiosyncratic drug reactions (e.g. agranulocytosis), liver necrosis or teratogenicity initiated by the cooxidation of endogenous substrates, plasma amino acids, drugs and xenobiotics catalysed by peroxidases or peroxidase containing cells have also been compared. Finally, peroxidase inhibitors currently in use for treating various diseases are described.

Animals↗

PubMed2000

Human acylation stimulating protein enhances triacylglycerol biosynthesis in plant microsomes.

Diacylglycerol acyltransferase has a universal role in catalyzing the acyl-CoA-dependent formation of triacylglycerol in microorganisms, animals and plants. Acylation stimulating protein, from human blood, is known to enhance diacylglycerol acyltransferase activity and triacylglycerol biosynthesis in human adipocytes. In the current study, acylation stimulating protein was also shown to enhance diacylglycerol acyltransferase activity in microsomes from cell suspension cultures of oilseed rape. Enzyme stimulation occurred over the pH range of 6-9 but the degree of stimulation decreased with increasing ionic strength at pH 7.4. Varying acyl-CoA concentration did not affect the degree of stimulation. Membranes from triacylglycerol producing cells in plants and humans may have similar binding sites for acylation stimulating protein which have been preserved during molecular evolution. The results suggest that human acylation stimulating protein may be useful in modifying lipid biosynthesis in plants.

Acyl Coenzyme A↗

PubMed2001

NADP-malic enzyme from plants: a ubiquitous enzyme involved in different metabolic pathways.

NADP-malic enzyme (NADP-ME) is a widely distributed enzyme that catalyzes the oxidative decarboxylation of L-malate. Photosynthetic NADP-MEs are found in C4 bundle sheath chloroplasts and in the cytosol of CAM plants, while non-photosynthetic NADP-MEs are either plastidic or cytosolic in various plants. We propose a classification of plant NADP-MEs based on their physiological function and localization and we describe recent advances in the characterization of each isoform. Based on the alignment of amino acid sequences of plant NADP-MEs, we identify putative binding sites for the substrates and analyze the phylogenetic origin of each isoform, revealing several features of the molecular evolution of this ubiquitous enzyme.

Amino Acid Sequence↗

PubMed2004

Hsp90 isoforms: functions, expression and clinical importance.

The 90 kDa heat shock protein, Hsp90, is a main functional component of an important cytoplasmic chaperone complex, and it is involved in various cellular processes, such as cell proliferation, differentiation and apoptosis. Identification of Hsp90 as a molecular target of various anticancer drugs highlighted its importance from the clinical point of view. Here we summarize the current knowledge of various Hsp90 isoforms regarding their genomic location, molecular evolution, functional differences, differential induction after various environmental stresses and in pathological conditions as well as the growing importance of discriminating between Hsp90 isoforms in clinical practice.

Animals↗

PubMed2004

Resolving the evolutionary paradox of genetic instability: a cost-benefit analysis of DNA repair in changing environments.

Loss of genetic stability is a critical phenomenon in cancer and antibiotic resistance, and the prevailing dogma is that unstable cells survive because instability provides adaptive mutations. Challenging this view, we have argued that genetic instability arises because DNA repair may be a counterproductive strategy in mutagenic environments. This paradoxical relationship has also been confirmed by explicit experiments, but the underlying evolutionary principles remain controversial. This paper aims to clarify the issue, and presents a model that explains genetic instability from the basic perspective of molecular evolution and information processing.

Animals↗

PubMed1997

COOH-terminal decamers in proteins are non-random.

We have undertaken an exhaustive statistical analysis of the amino acid sequences at the carboxyl-terminal (C) ends of proteins. The composition of the C-terminal decapeptides differs from that expected for the given proteins from the overall amino acid composition. For E. coli, yeast, and H. sapiens it was shown that positively charged amino acid residues are over-represented while Gly residues are under-represented. The C-terminal bias, a novel feature of protein structure, should be taken into account when molecular evolution, spatial structure, translational termination and protein folding are concerned.

Amino Acid Sequence↗

PubMed1999

Biochemical analysis of the interaction between elongation factor 1alpha and alpha/beta-tubulins from a ciliate, Tetrahymena pyriformis.

The interaction between elongation factor 1alpha (EF-1alpha) and alpha/beta-tubulins has been analyzed in vivo and in vitro. An association of both alpha- and beta-tubulins with EF-1alpha in the lysate of Tetrahymena pyriformis was detected by co-immunoprecipitation analysis. In contrast, in vitro biomolecular interaction analysis with glutathione S-transferase (GST) fusion proteins revealed that GST-beta-tubulin, but not GST-alpha-tubulin, can bind to GST-EF-1alpha. Two beta-tubulin binding sites have been identified to reside in the domains I and III of EF-1alpha. In addition, beta-tubulin itself seems to have two distinct interaction sites for each of the domains. Since domain II of EF-1alpha did not interact with beta-tubulin, we have re-evaluated the phylogenetic status of ciliates using EF-1alpha sequences devoid of domain II. The phylogenetic tree thus obtained was significantly different from that inferred from the whole sequence of EF-1alpha, suggesting the presence of functional constraints on the molecular evolution of EF-1alpha.

Animals↗

PubMed2000

Comparison of ribosomal DNA sequences of Lamellodiscus spp. (monogenea, diplectanidae) parasitising Pagellus (sparidae, teleostei) in the North Mediterranean Sea: species divergence and coevolutionary interactions.

We sequenced DNA fragments from four monogenean species of the genus Lamellodiscus and their three fish host species from the genus Pagellus in the North Mediterranean Sea, in order to estimate the molecular divergence and the coevolutionary interactions in this association. By comparing the ITS1 sequences of the parasites, we assessed their level of interspecific differences and tested the phylogenetic status of Lamellodiscus virgula and Lamellodiscus obeliae, formerly described as two different species. Moreover, we wanted to know if closely related parasites used closely related hosts, to investigate the coevolutionary interactions in this complex. Phylogenetic relationships among Lamellodiscus species were estimated with partial 18S ribosomal DNA sequences while mitochondrial cytochrome-b DNA sequences were used for their fish hosts. The ITS1 sequences appear to be highly variable among Lamellodiscus species, except L.virgula and L.obeliae, suggesting an old divergence time or a rapid molecular evolution within this genus. This fish-parasite association seems to exhibit coevolutionary interactions. L.virgula and L.obeliae are proposed to be a single species on the basis of their almost identical ITS1 sequences.

Animals↗

PubMed2003

Block structure and stability of the genetic code.

It is known that different codons may be unified into larger groups related to the hierarchical structure, approximate hidden symmetries, and evolutionary origin of the universal genetic code. Using a simplified evolutionary motivated two-letter version of genetic code, the general principles of the most stable coding are discussed. By the complete enumeration in such a reduced code it is strictly proved that the maximum stability with respect to point mutations and shifts in the reading frame needs the fixation of the middle letters within codons in groups with different physico-chemical properties, thus, explaining a key feature of the universal genetic code. The translational stability of the genetic code is studied by the mapping of code onto de Bruijn graph providing both the compact visual representation of mutual relationships between different codons as well as between codons and protein coding DNA sequence and a powerful tool for the investigation of stability of protein coding. Then, the results are extended to four-letter codes. As is shown, the universal genetic code obeys mainly the principles of optimal coding. These results demonstrate the hierarchical character of optimization of universal genetic code with strictly optimal coding being evolved at the earliest stages of molecular evolution. Finally, the universal genetic code is compared with the other natural variants of genetic codes.

Amino Acids↗