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PubMed2005

Estimating the time to the whole-genome duplication and the duration of concerted evolution via gene conversion in yeast.

A maximum-likelihood (ML) method is developed to estimate the duration of concerted evolution and the time to the whole-genome duplication (WGD) event in baker's yeast (Saccharomyces cerevisiae). The models with concerted evolution fit the data significantly better than the molecular clock model, indicating a crucial role of concerted evolution via gene conversion after gene duplication in yeast. Our ML estimate of the time to the WGD is nearly identical to the time to the speciation event between S. cerevisiae and Kluyveromyces waltii, suggesting that the WGD occurred in very early stages after speciation or the WGD might have been involved in the speciation event.

Algorithms↗
PubMed2000

Structure and function of mutationally generated monomers of dimeric phosphoribosylanthranilate isomerase from Thermotoga maritima.

BACKGROUND: Oligomeric proteins may have been selected for in hyperthermophiles because subunit association provides extra stabilization. Phosphoribosylanthranilate isomerase (PRAI) is monomeric and labile in most mesophilic microorganisms, but dimeric and stable in the hyperthermophile Thermotoga maritima (tPRAI). The two subunits of tPRAI are associated back-to-back and are locked together by a hydrophobic loop. The hypothesis that dimerization is important for thermostability has been tested by rationally designing monomeric variants of tPRAI. RESULTS: The comparison of tPRAI and PRAI from Escherichia coli (ePRAI) suggested that levelling the nonplanar dimer interface would weaken the association. The deletion of two residues in the loop loosened the dimer. Subsequent filling of the adjacent pocket and the exchange of polar for apolar residues yielded a weakly associating and a nonassociating monomeric variant. Both variants are as active as the parental dimer but far more thermolabile. The thermostability of the weakly associating monomer increased significantly with increasing protein concentration. The X-ray structure of the nonassociating monomer differed from that of the parental subunit only in the restructured interface. The orientation of the original subunits was maintained in a crystal contact between two monomers. CONCLUSIONS: tPRAI is dimeric for reasons of stability. The clearly separated responsibilities of the betaalpha loops, which are involved in activity, and the alphabeta loops, which are involved in protein stability, has permitted the evolution of dimers without compromising their activity. The preserved interaction in the crystal contacts suggests the most likely model for dimer evolution.

Aldose-Ketose Isomerases↗
PubMed2003

Hepatitis C virus dynamics and pathology: the role of CTL and antibody responses.

This paper investigates the role of CTL and antibody responses in hepatitis C virus (HCV) dynamics and pathology. Mathematical models suggest that a strong CTL response is required for resolution of HCV infection and that a weak CTL response can result in persistent infection. According to the model, establishment of persistent infection is accompanied mainly by an ongoing antibody response, while CTLs are not maintained at high levels. In the model, this outcome correlates with absence of pathology. Persistent infection in the face of an ongoing antibody response can result in evolution of antigenic escape. According to the model, evolution towards escape from antibodies can shift the balance of immune responses so that the weak CTL levels become increasingly more dominant relative to antibodies. This shift results in onset of liver pathology as the virus evolves towards increased levels of antigenic escape. Therefore, the relative balance of the immune response can be a decisive factor that determines whether patients are asymptomatic or whether pathology is observed. Virus evolution can shift this balance towards pathology over time. Theoretical results are discussed in the context of published data.

Acute Disease↗
PubMed1987

Ultrastructural study of the long-term development of two experimental cutaneous calcinoses (topical calciphylaxis and topical calcergy) in the rat.

Skin calcification induced by topical calciphylaxis was provoked by a subcutaneous injection of iron chloride in rats previously sensitized by dihydrotachysterol. A cutaneous topical calcergy was induced by an injection of potassium permanganate. An electron-microscopical study of the long-term evolution of both these models of calcification was made. After the initial stages, mineralization of the connective tissue continued by a secondary nucleation process without matrix vesicles. The mineral composed of needle-like structures, apatite in nature, was mainly deposited between and around collagen fibrils, and showed various arrangements in calcified plaques. Intrafibrillar calcification was rarely observed and appeared only in the later stages. The extension of calcified deposits then stopped. Finally, there was a fragmentation of the mineralized area which was progressively surrounded by uncalcified collagen fibrils. A demineralization process, caused by cells such as macrophages and multinucleated giant cells, rather than a resorption of the calcified deposits, was noted. It is important to emphasize that, in both models of ectopic calcification, an evolution toward ectopic ossification was never observed, which is perhaps due to the absence of extensive resorption mechanisms.

Animals↗
PubMed2003

Continuous in vitro evolution of ribozymes that operate under conditions of extreme pH.

Continuous in vitro evolution methods were used to study the behavior of an evolving population of RNA ligase ribozymes in response to selection pressures involving conditions of extreme pH. The starting population consisted of randomized variants of a ribozyme that had been optimized for activity at pH 8.5. The ribozymes were subjected to repeated rounds of selective amplification under progressively more acidic or more alkaline conditions. The two final evolved populations of ribozymes were able to operate at either pH 5.8 or pH 9.8, respectively. Representative individuals from the two final populations were isolated and characterized. The low-pH ribozyme exhibited a 10-fold increase in catalytic rate at pH 5.8 compared to the starting molecule. The high-pH ribozyme retained its structural integrity and activity at pH 9.8, whereas the starting molecule was denatured under this condition. These findings demonstrate that a population of functional macromolecules can adapt to stringent environmental conditions through the acquisition of relatively few mutations. The results establish continuous in vitro evolution as a useful model system for exploring the evolution of enzymatic function in extreme environments.

Base Sequence↗
PubMed2001

Of mice and genome sequence.

Availability of the mouse genome sequence will have a major impact on the study of vertebrate evolution, mammalian biology, and animal models of human disease. Resources to explore genome biology in mice will maximize the effect of this watershed event.

Animals↗
PubMed2001

The crystal structure of a heptameric archaeal Sm protein: Implications for the eukaryotic snRNP core.

Sm proteins form the core of small nuclear ribonucleoprotein particles (snRNPs), making them key components of several mRNA-processing assemblies, including the spliceosome. We report the 1.75-A crystal structure of SmAP, an Sm-like archaeal protein that forms a heptameric ring perforated by a cationic pore. In addition to providing direct evidence for such an assembly in eukaryotic snRNPs, this structure (i) shows that SmAP homodimers are structurally similar to human Sm heterodimers, (ii) supports a gene duplication model of Sm protein evolution, and (iii) offers a model of SmAP bound to single-stranded RNA (ssRNA) that explains Sm binding-site specificity. The pronounced electrostatic asymmetry of the SmAP surface imparts directionality to putative SmAP-RNA interactions.

Amino Acid Sequence↗
PubMed2000

In the african lungfish Met-enkephalin and leu-enkephalin are derived from separate genes: cloning of a proenkephalin cDNA.

A full-length proenkephalin cDNA (accession number: AF232670) was cloned from an African lungfish (Protopterus annectens) brain cDNA library. The 1,351-bp African lungfish proenkephalin contains an open reading frame that codes 266 amino acids and a stop codon. Within the sequence of lungfish proenkephalin there are 5 pentapeptide opioid sequences (all YGGFM), 1 octapeptide opioid sequence (YGGFMRSL) and 1 heptapeptide opioid sequence (YGGFMGY). A Leu-enkephalin sequence was conspicuously absent in lungfish proenkephalin. These results, coupled with observations on the organization of amphibian proenkephalin and mammalian proenkephalin, indicate that among the Sarcopterygii (lobed finned fish and tetrapods), the appearance of a Leu-enkephalin sequence in proenkephalin may have evolved in either the ancestral amniotes or the ancestral mammals, but not earlier in sarcopterygian evolution. Furthermore, the detection of neurons in the lungfish CNS that are only immunopositive for Met-enkephalin, coupled with earlier anatomical studies on the presence of neurons in the lungfish CNS that are only immunopositive for Leu-enkephalin, indicates that a Leu-enkephalin-coding opioid gene must be present in the CNS of the lungfish. This gene may be the lungfish form of prodynorphin. Given the phylogenetic position of the lungfish in vertebrate evolution, the putative Leu-enkephalin-coding gene must have evolved in the ancestral sarcopterygian vertebrates, or in the ancestral gnathostomes. The apparent slow rate of lungfish evolution makes these organisms interesting models for investigating the evolution of the opioid/orphanin gene family.

Amino Acid Sequence↗
PubMed1997

On the evolution of density dependent dispersal in a spatially structured population model.

A simple metapopulation lattice model of two competing phenotypes is presented, where one phenotype reacts more sensitively to overcrowding by migrating to neighbouring local habitats. The sensitivity is formulated by means of a threshold density of the subpopulations, above which dispersal is triggered off. If this threshold density is not very far from the local carrying capacity, an increased mobility provides benefits on the metapopulation level. At a surprisingly small difference between migrational triggering thresholds, the phenotype of larger mobility (or lower threshold) squeezes out the less mobile one from the whole system in a wide parameter range. Evolutionary considerations give an optimal threshold level for our model metapopulation.

Animals↗
PubMed2000

The other "closest living relative". How bonobos (Pan paniscus) challenge traditional assumptions about females, dominance, intra- and intersexual interactions, and hominid evolution.

Chimpanzee (Pan troglodytes) societies are typically characterized as physically aggressive, male-bonded and male-dominated. Their close relatives, the bonobos (Pan paniscus), differ in startling and significant ways. For instance, female bonobos bond with one another, form coalitions, and dominate males. A pattern of reluctance to consider, let alone acknowledge, female dominance in bonobos exists, however. Because both species are equally "man's" closest relative, the bonobo social system complicates models of human evolution that have historically been based upon referents that are male and chimpanzee-like. The bonobo evidence suggests that models of human evolution must be reformulated such that they also accommodate: real and meaningful female bonds; the possibility of systematic female dominance over males; female mating strategies which encompass extra-group paternities; hunting and meat distribution by females; the importance of the sharing of plant foods; affinitive inter-community interactions; males that do not stalk and attack and are not territorial; and flexible social relationships in which philopatry does not necessarily predict bonding pattern.

Animals↗
PubMed2006

Symbiotic adaptive neuro-evolution applied to rainfall-runoff modelling in northern England.

This paper uses a symbiotic adaptive neuro-evolutionary algorithm to breed neural network models for the River Ouse catchment. It advances on traditional evolutionary approaches by evolving and optimising individual neurons. Furthermore, it is ideal for experimentation with alternative objective functions. Recent research suggests that sum squared error may not result in the most appropriate models from a hydrological perspective. Models are bred for lead times of 6 and 24 hours and compared with conventional neural network models trained using backpropagation. The algorithm is also modified to use different objective functions in the optimisation process: mean squared error, relative error and the Nash-Sutcliffe coefficient of efficiency. The results show that at longer lead times the evolved neural networks outperform the conventional ones in terms of overall performance. It is also shown that the sum squared error objective function does not result in the best performing model from a hydrological perspective.

Algorithms↗
PubMed2006

The development of archosaurian first-generation teeth in a chicken mutant.

Modern birds do not have teeth. Rather, they develop a specialized keratinized structure, called the rhamphotheca, that covers the mandible, maxillae, and premaxillae. Although recombination studies have shown that the avian epidermis can respond to tooth-inductive cues from mouse or lizard oral mesenchyme and participate in tooth formation, attempts to initiate tooth development de novo in birds have failed. Here, we describe the formation of teeth in the talpid2 chicken mutant, including the developmental processes and early molecular changes associated with the formation of teeth. Additionally, we show recapitulation of the early events seen in talpid2 after in vivo activation of beta-catenin in wild-type embryos. We compare the formation of teeth in the talpid2 mutant with that in the alligator and show the formation of decidedly archosaurian (crocodilian) first-generation teeth in an avian embryo. The formation of teeth in the mutant is coupled with alterations in the specification of the oral/aboral boundary of the jaw. We propose an epigenetic model of the developmental modification of dentition in avian evolution; in this model, changes in the relative position of a lateral signaling center over competent odontogenic mesenchyme led to loss of teeth in avians while maintaining tooth developmental potential.

Alligators and Crocodiles↗
PubMed2000

Neutral and nonneutral mitochondrial genetic variation in deep-sea clams from the family vesicomyidae.

Nucleotide sequences at two mitochondrial genes from 57 individuals representing eight species of deep-sea clams (Vesicomyidae) were examined for variation consistent with the neutral model of molecular evolution. One gene, cytochrome oxidase subunit I (COI), deviated from the expectations of neutrality by containing an excess of intraspecific nonsynonymous polymorphism. Additionally, one species, Calyptogena kilmeri, showed a significant excess of rare polymorphism specifically at the COI locus. In contrast, a second mitochondrial gene, the large-subunit 16S ribosomal RNA gene (16S), showed little deviation from neutrality either between or within species. Together, COI and 16S show no deviation from neutral expectations by the HKA test, produce congruent phylogenetic relationships between species, and show correlated numbers of fixed differences between species and polymorphism within species. These patterns of both neutral and nonneutral evolution within the mitochondrial genome are most consistent with a model where intraspecific nonsynonymous polymorphism at COI is near neutrality. In addition to examining the forces of molecular evolution, we extend hypotheses about interspecific relationships within this family for geographical locations previously unexamined by molecular methods including habitats near the Middle Atlantic, the Aleutian Trench, and Costa Rica.

Animals↗
PubMedDate not supplied

Mathematical stochastic models of some typical viral epidemiological evolutions.

The formalisms of the probability distribution and of the associated generator function are used to establish the equations for the first and second moments of the numbers of susceptible and contagious individuals. Applications are given for the linear cases for the epidemic evolutions, for the endemic situations and for virosis in course of eradication.

Disease Outbreaks↗
PubMed1998

Ribosomal protein structures: insights into the architecture, machinery and evolution of the ribosome.

Models of the bacterial ribosome based on recent structural analyses are beginning to provide new insights into the protein synthetic machinery. Central to evolving models are the high-resolution structures of individual ribosomal proteins, which represent detailed probes of their local RNA and protein environments. Ribosomal proteins are extremely ancient molecules; the structures therefore also provide a unique window into early protein evolution. Many of the proteins contain domains that are present in more recently evolved families of RNA- and DNA-binding proteins. Such structural homology can be used to predict mechanisms by which proteins interact with RNA in the ribosome.

Bacteria↗
PubMed2003

Pandit: a database of protein and associated nucleotide domains with inferred trees.

MOTIVATION: A large, high-quality database of homologous sequence alignments with good estimates of their corresponding phylogenetic trees will be a valuable resource to those studying phylogenetics. It will allow researchers to compare current and new models of sequence evolution across a large variety of sequences. The large quantity of data may provide inspiration for new models and methodology to study sequence evolution and may allow general statements about the relative effect of different molecular processes on evolution. RESULTS: The Pandit 7.6 database contains 4341 families of sequences derived from the seed alignments of the Pfam database of amino acid alignments of families of homologous protein domains (Bateman et al., 2002). Each family in Pandit includes an alignment of amino acid sequences that matches the corresponding Pfam family seed alignment, an alignment of DNA sequences that contain the coding sequence of the Pfam alignment when they can be recovered (overall, 82.9% of sequences taken from Pfam) and the alignment of amino acid sequences restricted to only those sequences for which a DNA sequence could be recovered. Each of the alignments has an estimate of the phylogenetic tree associated with it. The tree topologies were obtained using the neighbor joining method based on maximum likelihood estimates of the evolutionary distances, with branch lengths then calculated using a standard maximum likelihood approach.

Algorithms↗
PubMed1993

Empirical and structural models for insertions and deletions in the divergent evolution of proteins.

The exhaustive matching of the protein sequence database makes possible a broadly based study of insertions and deletions (indels) during divergent evolution. In this study, the probability of a gap in an alignment of a pair of homologous protein sequences was found to increase with the evolutionary distance measured in PAM units (number of accepted point mutations per 100 amino acid residues). A relationship between the average number of amino acid residues between indels and evolutionary distance suggests that a unit 30 to 40 amino acid residues in length remains, on average, undisrupted by indels during divergent evolution. Further, the probability of a gap was found to be inversely proportional to gap length raised to the 1.7 power. This empirical law fits closely over the entire range of gap lengths examined. Gap length distribution is largely independent of evolutionary distance. These results rule out the widely used linear gap penalty as a satisfactory formula for scoring gaps when constructing alignments. Further, the observed gap length distribution can be explained by a simple model of selective pressures governing the acceptance of indels during divergent evolution. Finally, this model provides theoretical support for using indels as part of "parsing algorithms", important in the de novo prediction of the folded structure of proteins from the sequence data.

Amino Acid Sequence↗