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PubMed2006

Paucity of CD4+CCR5+ T cells is a typical feature of natural SIV hosts.

In contrast to lentiviral infections of humans and macaques, simian immunodeficiency virus (SIV) infection of natural hosts is nonpathogenic despite high levels of viral replication. However, the mechanisms underlying this absence of disease are unknown. Here we report that natural hosts for SIV infection express remarkably low levels of CCR5 on CD4+ T cells isolated from blood, lymph nodes, and mucosal tissues. Given that this immunologic feature is found in 5 different species of natural SIV hosts (sooty mangabeys, African green monkeys, mandrills, sun-tailed monkeys, and chimpanzees) but is absent in 5 nonnatural/recent hosts (humans, rhesus, pigtail, cynomolgus macaques, and baboons), it may represent a key feature of the coevolution between the virus and its natural hosts that led to a nonpathogenic infection. Beneficial effects of low CCR5 expression on CD4+ T cells may include the reduction of target cells for viral replication and a decreased homing of activated CD4+ T cells to inflamed tissue.

Animals↗

PubMed2005

Lineage-specific variations of congruent evolution among DNA sequences from three genomes, and relaxed selective constraints on rbcL in Cryptomonas (Cryptophyceae).

BACKGROUND: Plastid-bearing cryptophytes like Cryptomonas contain four genomes in a cell, the nucleus, the nucleomorph, the plastid genome and the mitochondrial genome. Comparative phylogenetic analyses encompassing DNA sequences from three different genomes were performed on nineteen photosynthetic and four colorless Cryptomonas strains. Twenty-three rbcL genes and fourteen nuclear SSU rDNA sequences were newly sequenced to examine the impact of photosynthesis loss on codon usage in the rbcL genes, and to compare the rbcL gene phylogeny in terms of tree topology and evolutionary rates with phylogenies inferred from nuclear ribosomal DNA (concatenated SSU rDNA, ITS2 and partial LSU rDNA), and nucleomorph SSU rDNA. RESULTS: Largely congruent branching patterns and accelerated evolutionary rates were found in nucleomorph SSU rDNA and rbcL genes in a clade that consisted of photosynthetic and colorless species suggesting a coevolution of the two genomes. The extremely accelerated rates in the rbcL phylogeny correlated with a shift from selection to mutation drift in codon usage of two-fold degenerate NNY codons comprising the amino acids asparagine, aspartate, histidine, phenylalanine, and tyrosine. Cysteine was the sole exception. The shift in codon usage seemed to follow a gradient from early diverging photosynthetic to late diverging photosynthetic or heterotrophic taxa along the branches. In the early branching taxa, codon preferences were changed in one to two amino acids, whereas in the late diverging taxa, including the colorless strains, between four and five amino acids showed changes in codon usage. CONCLUSION: Nucleomorph and plastid gene phylogenies indicate that loss of photosynthesis in the colorless Cryptomonas strains examined in this study possibly was the result of accelerated evolutionary rates that started already in photosynthetic ancestors. Shifts in codon usage are usually considered to be caused by changes in functional constraints and in gene expression levels. Thus, the increasing influence of mutation drift on codon usage along the clade may indicate gradually relaxed constraints and reduced expression levels on the rbcL gene, finally correlating with a loss of photosynthesis in the colorless Cryptomonas paramaecium strains.

Asparagine↗

PubMed2006

Deep mtDNA divergences indicate cryptic species in a fig-pollinating wasp.

BACKGROUND: Figs and fig-pollinating wasps are obligate mutualists that have coevolved for ca. 90 million years. They have radiated together, but do not show strict cospeciation. In particular, it is now clear that many fig species host two wasp species, so there is more wasp speciation than fig speciation. However, little is known about how fig wasps speciate. RESULTS: We studied variation in 71 fig-pollinating wasps from across the large geographic range of Ficus rubiginosa in Australia. All wasps sampled belong to one morphological species (Pleistodontes imperialis), but we found four deep mtDNA clades that differed from each other by 9-17% nucleotides. As these genetic distances exceed those normally found within species and overlap those (10-26%) found between morphologically distinct Pleistodontes species, they strongly suggest cryptic fig wasp species. mtDNA clade diversity declines from all four present in Northern Queensland to just one in Sydney, near the southern range limit. However, at most sites multiple clades coexist and can be found in the same tree or even the same fig fruit and there is no evidence for parallel sub-division of the host fig species. Both mtDNA data and sequences from two nuclear genes support the monophyly of the "P. imperialis complex" relative to other Pleistodontes species, suggesting that fig wasp divergence has occurred without any host plant shift. Wasps in clade 3 were infected by a single strain (W1) of Wolbachia bacteria, while those in other clades carried a double infection (W2+W3) of two other strains. CONCLUSION: Our study indicates that cryptic fig-pollinating wasp species have developed on a single host plant species, without the involvement of host plant shifts, or parallel host plant divergence. Despite extensive evidence for coevolution between figs and fig wasps, wasp speciation may not always be linked strongly with fig speciation.

Animals↗

PubMed2007

Differential impact of simultaneous migration on coevolving hosts and parasites.

BACKGROUND: The dynamics of antagonistic host-parasite coevolution are believed to be crucially dependent on the rate of migration between populations. We addressed how the rate of simultaneous migration of host and parasite affected resistance and infectivity evolution of coevolving meta-populations of the bacterium Pseudomonas fluorescens and a viral parasite (bacteriophage). The increase in genetic variation resulting from small amounts of migration is expected to increase rates of adaptation of both host and parasite. However, previous studies suggest phages should benefit more from migration than bacteria; because in the absence of migration, phages are more genetically limited and have a lower evolutionary potential compared to the bacteria. RESULTS: The results supported the hypothesis: migration increased the resistance of bacteria to their local (sympatric) hosts. Moreover, migration benefited phages more than hosts with respect to 'global' (measured with respect to the whole range of migration regimes) patterns of resistance and infectivity, because of the differential evolutionary responses of bacteria and phage to different migration regimes. Specifically, we found bacterial global resistance peaked at intermediate rates of migration, whereas phage global infectivity plateaued when migration rates were greater than zero. CONCLUSION: These results suggest that simultaneous migration of hosts and parasites can dramatically affect the interaction of host and parasite. More specifically, the organism with the lower evolutionary potential may gain the greater evolutionary advantage from migration.

Biological Evolution↗

PubMed2002

The repertoire of protein kinases encoded in the draft version of the human genome: atypical variations and uncommon domain combinations.

BACKGROUND: Phosphorylation by protein kinases is central to cellular signal transduction. Abnormal functioning of kinases has been implicated in developmental disorders and malignancies. Their activity is regulated by second messengers and by the binding of associated domains, which are also influential in translocating the catalytic component to their substrate sites, in mediating interaction with other proteins and carrying out their biological roles. RESULT: Using sensitive profile-search methods and manual analysis, the human genome has been surveyed for protein kinases. A set of 448 sequences, which show significant similarity to protein kinases and contain the critical residues essential for kinase function, have been selected for an analysis of domain combinations after classifying the kinase domains into subfamilies. The unusual domain combinations in particular kinases suggest their involvement in ubiquitination pathways and alternative modes of regulation for mitogen-activated protein kinase kinases (MAPKKs) and cyclin-dependent kinase (CDK)-like kinases. Previously unexplored kinases have been implicated in osteoblast differentiation and embryonic development on the basis of homology with kinases of known functions from other organisms. Kinases potentially unique to vertebrates are involved in highly evolved processes such as apoptosis, protein translation and tyrosine kinase signaling. In addition to coevolution with the kinase domain, duplication and recruitment of non-catalytic domains is apparent in signaling domains such as the PH, DAG-PE, SH2 and SH3 domains. CONCLUSIONS: Expansion of the functional repertoire and possible existence of alternative modes of regulation of certain kinases is suggested by their uncommon domain combinations. Experimental verification of the predicted implications of these kinases could enhance our understanding of their biological roles.

Amino Acid Motifs↗

PubMed2005

Viral strategies for evading antiviral cellular immune responses of the host.

The host invariably responds to infecting viruses by activating its innate immune system and mounting virus-specific humoral and cellular immune responses. These responses are aimed at controlling viral replication and eliminating the infecting virus from the host. However, viruses have evolved numerous strategies to counter and evade host's antiviral responses. Providing specific examples from the published literature, we discuss in this review article various strategies that viruses have developed to evade antiviral cellular responses of the host. Unraveling these viral strategies allows a better understanding of the host-pathogen interactions and their coevolution. This knowledge is important for identifying novel molecular targets for developing antiviral reagents. Finally, it may also help devise new knowledge-based strategies for developing antiviral vaccines.

Animals↗

PubMed2005

Relaxin research in the postgenomic era.

Because of the coevolution of ligands and their cognate receptors, analysis of human genomic sequences allows prediction of the pairing of these elements. Initially, we identified a group of five human leucine-rich repeat-containing G-protein-coupled receptor (LGR) genes homologous to LH, FSH, and TSH receptors. Based on common phenotypes of INSL3 null mice and transgenic mice with LGR8 gene deletion, we hypothesized that INSL3, relaxin, and related genes are likely ligands for the paralogous LGR7 and LGR8 genes. Matching the relaxin family peptides with these two orphan LGRs led to the finding that relaxin is capable of activating LGR7 and LGR8 through the Gs pathway. In addition, INSL3 and relaxin 3 were found to be specific ligands for LGR8 and LGR7, respectively. Based on the known production of INLS3 by testicular Leydig cells and ovarian theca cells, we demonstrated the expression of the INSL3 receptor LGR8 in oocytes in ovary and in male germ cells in the testis. Furthermore, we found that LH stimulates INSL3 transcripts in ovarian theca and testicular Leydig cells. INSL3, in turn, binds LGR8 expressed in germ cells to initiate the meiotic progression of arrested oocytes in preovulatory follicles in vitro and in vivo and to suppress male germ cell apoptosis in vivo. INSL3 interacts with germ cells to activate the inhibitory G protein, thus leading to decreases in cAMP production. Our data demonstrate the importance of the INSL3-LGR8 paracrine system in mediating gonadotropic actions in both ovary and testis.

Animals↗

PubMed2004

Evolutionary fuzzy modeling human diagnostic decisions.

Fuzzy CoCo is a methodology, combining fuzzy logic and evolutionary computation, for constructing systems able to accurately predict the outcome of a human decision-making process, while providing an understandable explanation of the underlying reasoning. Fuzzy logic provides a formal framework for constructing systems exhibiting both good numeric performance (accuracy) and linguistic representation (interpretability). However, fuzzy modeling--meaning the construction of fuzzy systems--is an arduous task, demanding the identification of many parameters. To solve it, we use evolutionary computation techniques (specifically cooperative coevolution), which are widely used to search for adequate solutions in complex spaces. We have successfully applied the algorithm to model the decision processes involved in two breast cancer diagnostic problems, the WBCD problem and the Catalonia mammography interpretation problem, obtaining systems both of high performance and high interpretability. For the Catalonia problem, an evolved system was embedded within a Web-based tool-called COBRA-for aiding radiologists in mammography interpretation.

Breast Neoplasms↗

PubMed2005

Evolution of the pregnane x receptor: adaptation to cross-species differences in biliary bile salts.

The pregnane X receptor (PXR) regulates the metabolism and elimination of bile salts, steroids, and xenobiotics. The sequence of the PXR ligand-binding domain diverges extensively between different animals, suggesting interspecies differences in ligands. Of the endogenous ligands known to activate PXR, biliary bile salts vary the most across vertebrate species, ranging from 27-carbon (C27) bile alcohol sulfates (early fish, amphibians) to C24 bile acids (birds, mammals). Using a luciferase-based reporter assay, human PXR was activated by a wide variety of bile salts. In contrast, zebrafish PXR was activated efficiently only by cyprinol sulfate, the major zebrafish bile salt, but not by recent bile acids. Chicken, mouse, rat, and rabbit PXRs were all activated by species-specific bile acids and by early fish bile alcohol sulfates. In addition, phylogenetic analysis using maximum likelihood demonstrated evidence for nonneutral evolution of the PXR ligand-binding domain. PXR activation by bile salts has expanded from narrow specificity for C27 bile alcohol sulfates (early fish) to a broader specificity for recent bile acids (birds, mammals). PXR specificity for bile salts has thus paralleled the increasing complexity of the bile salt synthetic pathway during vertebrate evolution, an unusual example of ligand-receptor coevolution in the nuclear hormone receptor superfamily.

Animals↗

PubMed2004

Detection of genome-scale ordered RNA structure (GORS) in genomes of positive-stranded RNA viruses: Implications for virus evolution and host persistence.

Discrete RNA secondary and higher-order structures, typically local in extent, play a fundamental role in RNA virus replication. Using new bioinformatics analysis methods, we have identified genome-scale ordered RNA structure (GORS) in many genera and families of positive-strand animal and plant RNA viruses. There was remarkably variability between genera that possess this characteristic; for example, hepaciviruses in the family Flaviviridae show evidence for extensive internal base-pairing throughout their coding sequences that was absent in both the related pestivirus and flavivirus genera. Similar genus-associated variability was observed in the Picornaviridae, the Caliciviridae, and many plant virus families. The similarity in replication strategies between genera in each of these families rules out a role for GORS in a fundamentally conserved aspect of this aspect of the virus life cycle. However, in the Picornaviridae, Flaviviridae, and Caliciviridae, the existence of GORS correlated strongly with the ability of each genus to persist in their natural hosts. This raises the intriguing possibility of a role for GORS in the modulation of innate intracellular defense mechanisms (and secondarily, the acquired immune system) triggered by double-stranded RNA, analogous in function to the expression of structured RNA transcripts by large DNA viruses. Irrespective of function, the observed evolutionary conservation of GORS in many viruses imposes a considerable constraint on genome plasticity and the consequent narrowing of sequence space in which neutral drift can occur. These findings potentially reconcile the rapid evolution of RNA viruses over short periods with the documented examples of extreme conservatism evident from their intimate coevolution with their hosts.

Animals↗

PubMed2001

Evolutionary biology of plant defenses against herbivory and their predictive implications for endocrine disruptor susceptibility in vertebrates.

Hormone disruption is a major, underappreciated component of the plant chemical arsenal, and the historical coevolution between hormone-disrupting plants and herbivores will have both increased the susceptibility of carnivores and diversified the sensitivities of herbivores to man-made endocrine disruptors. Here I review diverse evidence of the influence of plant secondary compounds on vertebrate reproduction, including human reproduction. Three of the testable hypotheses about the evolutionary responses of vertebrate herbivores to hormone-disrupting challenges from their diet are developed. Specifically, the hypotheses are that a) vertebrate herbivores will express steroid hormone receptors in the buccal cavity and/or the vomeronasal organ; b) absolute sex steroid concentrations will be lower in carnivores than in herbivores; and c) herbivore steroid receptors should be more diverse in their binding affinities than carnivore lineages. The argument developed in this review, if empirically validated by support for the specific hypotheses, suggests that a) carnivores will be more susceptible than herbivores to endocrine-disrupting compounds of anthropogenic origin entering their bodies, and b) diverse herbivore lineages will be variably susceptible to any given natural or synthetic contaminant. As screening methods for hormone-disrupting potential are compared and adopted, comparative endocrine physiology research is urgently needed to develop models that predict the broad applicability of those screening results in diverse vertebrate species.

Adaptation, Physiological↗

PubMed2006

Evoecotoxicology: environmental changes and life features development during the evolutionary process-the record of the past at developmental stages of living organisms.

For most of evolutionary history, scientific understanding of the environment and life forms is extremely limited. In this commentary I discuss the hypothesis that ontogenetic features of living organisms can be considered biomarkers of coevolution between organisms and physicochemical agents during Earth's history. I provide a new vision of evolution based on correlations between metabolic features and stage-dependent susceptibility of organisms to physicochemical agents with well-known environmental signatures. Thus, developmental features potentially reflect environmental changes during evolution. From this perspective, early multicellular life forms would have flourished in the anoxic Earth more than 2 billion years ago, which is at least 1.2 billion years in advance of available fossil evidence. The remarkable transition to aerobic metabolism in gastrula-stage embryos potentially reflects evolution toward tridermic organisms by 2 billion years ago. Noteworthy changes in embryonic resistance to physicochemical agents at different developmental stages that can be observed in living organisms potentially reflect the influence of environmental stress conditions during different periods of evolutionary history. Evoecotoxicology, as a multidisciplinary and transdisciplinary approach, can enhance our understanding of evolution, including the phylogenetic significance of differences in susceptibility/resistance to physicochemical agents in different organisms.

Animals↗

PubMed1996

Phylogenetic analysis of the 16S-23S rRNA intergenic spacer regions of the genus Ureaplasma.

The nucleotide sequences of the spacer regions between the 16S and 23S rRNA genes of six Ureaplasma species were determined following amplification by polymerase chain reaction. The hypothetical secondary structure of the spacer regions was divided into four domains. Domains I and III were highly conserved among different Ureaplasma species but domains II and IV were variable. The intergenic spacer regions of ureaplasmas lacked spacer tRNA genes. Phylogenetic relationships among the Ureaplasma species indicated that the evolutionary history of the Ureaplasma species follows that of the host animal species, suggesting coevolution between ureaplasmas and animals.

Animals↗

PubMed2006

Ancient host-pathogen associations maintained by specificity of chemotaxis and antibiosis.

Switching by parasites to novel hosts has profound effects on ecological and evolutionary disease dynamics. Switching requires that parasites are able to establish contact with novel hosts and to overcome host defenses. For most host-parasite associations, it is unclear as to what specific mechanisms prevent infection of novel hosts. Here, we show that parasitic fungal species in the genus Escovopsis, which attack and consume the fungi cultivated by fungus-growing ants, are attracted to their hosts via chemotaxis. This response is host-specific: Escovopsis spp. grow towards their natural host cultivars more rapidly than towards other closely related fungi. Moreover, the cultivated fungi secrete compounds that can suppress Escovopsis growth. These antibiotic defenses are likewise specific: in most interactions, cultivars can inhibit growth of Escovopsis spp. not known to infect them in nature but cannot inhibit isolates of their naturally infecting pathogens. Cases in which cultivars are susceptible to novel Escovopsis are limited to a narrow set of host-parasite strain combinations. Targeted chemotactic and antibiotic responses therefore explain why Escovopsis pathogens do not readily switch to novel hosts, consequently constraining long-term dynamics of host-parasite coevolution within this ancient association.

Animals↗

PubMed2005

SARS transmission pattern in Singapore reassessed by viral sequence variation analysis.

BACKGROUND: Epidemiological investigations of infectious disease are mainly dependent on indirect contact information and only occasionally assisted by characterization of pathogen sequence variation from clinical isolates. Direct sequence analysis of the pathogen, particularly at a population level, is generally thought to be too cumbersome, technically difficult, and expensive. We present here a novel application of mass spectrometry (MS)-based technology in characterizing viral sequence variations that overcomes these problems, and we apply it retrospectively to the severe acute respiratory syndrome (SARS) outbreak in Singapore. METHODS AND FINDINGS: The success rate of the MS-based analysis for detecting SARS coronavirus (SARS-CoV) sequence variations was determined to be 95% with 75 copies of viral RNA per reaction, which is sufficient to directly analyze both clinical and cultured samples. Analysis of 13 SARS-CoV isolates from the different stages of the Singapore outbreak identified nine sequence variations that could define the molecular relationship between them and pointed to a new, previously unidentified, primary route of introduction of SARS-CoV into the Singapore population. Our direct determination of viral sequence variation from a clinical sample also clarified an unresolved epidemiological link regarding the acquisition of SARS in a German patient. We were also able to detect heterogeneous viral sequences in primary lung tissues, suggesting a possible coevolution of quasispecies of virus within a single host. CONCLUSION: This study has further demonstrated the importance of improving clinical and epidemiological studies of pathogen transmission through the use of genetic analysis and has revealed the MS-based analysis to be a sensitive and accurate method for characterizing SARS-CoV genetic variations in clinical samples. We suggest that this approach should be used routinely during outbreaks of a wide variety of agents, in order to allow the most effective control.

DNA, Viral↗

PubMed2007

Synthesis of degenerated libraries of the ras-binding domain of raf and rapid selection of fast-folding and stable clones with the dihydrofolate reductase protein fragment complementation assay.

The protein-engineering field is mainly concerned with the design of novel enzyme activities or folds and with understanding the fundamental sequence determinants of protein folding and stability. Much effort has been put into the design of methods to generate and screen libraries of polypeptides. Screening for the ability of proteins to bind with high affinity and/or specificity is most often approached with phage display technologies. In this chapter, we present an alternative to phage display, performed totally in vivo, based on the dihydrofolate reductase (DHFR) protein-fragment complementation assay (PCA). We describe the application of the DHFR PCA to the selection of degenerated sequences of the ras-binding domain (RBD) of raf for correct folding and binding to ras. Our screening system allows for enrichment of the libraries for the best-behaving sequences through iterative competition experiments, without the discrete library screening and expansion steps that are necessary in in vitro approaches. Moreover, the selected clones can be processed rapidly to purification by Ni-nitrilotriacetic acid (NTA) affinity chromatography in 96-well plates. Our methods are particularly suitable for the designing and screening of libraries aimed at studying sequence folding and binding determinants. Finally, it can be adapted for library-against-library screening, thus, allowing for coevolution of interacting proteins simultaneously.

Chromatography, Affinity↗

PubMed2003

Efficient display of two enzymes on filamentous phage using an improved signal sequence.

Directed protein-evolution strategies generally make use of a link between a protein and the encoding DNA. In phage-display technology, this link is provided by fusion of the protein with a coat protein that is incorporated into the phage particle containing the DNA. Optimization of this link can be achieved by adjusting the signal sequence of the fusion. In a previous study, directed evolution of signal sequences for optimal display of the Taq DNA polymerase I Stoffel fragment on phage yielded signal peptides with a 50- fold higher incorporation of fusion proteins in phage particles. In this article, we show that for one of the selected signal sequences, improved display on phage can be generalized to other proteins, such as adenylate cyclases from Escherichia coli and Bordetella pertussis, and that this is highly dependent on short sequences at the C-terminus of the signal peptide. Further, the display of two enzymes on phage has been achieved and may provide a strategy for directing coevolution of the two proteins. These findings should be useful for display of large and cytoplasmic proteins on filamentous phage.

Adenylyl Cyclases↗

PubMed2004

The capsalidae (Monogenea: Monopisthocotylea): a review of diversity, classification and phylogeny with a note about species complexes.

The Capsalidae are monogeneans parasitizing 'skin', fins and gills of marine fishes. Some capsalids are pathogenic to cultivated fish and a few have caused epizootic events. It is a cosmopolitan family with broad host associations (elasmobranchs and teleosts, including sturgeons). Approximately 200 capsalid species are placed in nine subfamilies and 44-46 genera, some of which are well known (Benedenia, Capsala, Entobdella, Neobenedenia). Sturgeons host two capsalid species (Nitzschiinae) and 15 species in five genera are reliably reported from elasmobranchs. The combination of ancient (shark, ray, sturgeon) and modem (teleost) host fish lineages indicates that capsalid evolution is likely a blend of coevolution and host-switching, but a family phylogeny has been lacking due to deficient knowledge about homologies. The current phenetic subfamilial classification is discussed in detail using a preliminary phylogeny generated from large subunit ribosomal DNA sequence data from representatives of five subfamilies. Monophyly of the Capsalidae is supported by possession of accessory sclerites. Hypotheses are proposed for the possible radiation of capsalids. A suggestion that Neobenedenia melleni, a pathogenic species atypical due to its broad host-specificity (>100 host teleost species from >30 families in five orders), may be a complex of species is supported from genetic evidence. This may explain peculiarities in biology, taxonomy, host associations and geographic distribution of N. 'melleni' and has implications for fish health. Holistic studies using live and preserved larval and adult capsalid specimens and material for genetic analysis are emphasised to further determine identity, phylogeny and details of biology, especially for pathogenic species.

Animals↗