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PubMed2003

Sequence diversity of Treponema pallidum subsp. pallidum tprK in human syphilis lesions and rabbit-propagated isolates.

The tprK gene of Treponema pallidum subsp. pallidum, the causative agent of venereal syphilis, belongs to a 12-member gene family and encodes a protein with a predicted cleavable signal sequence and predicted transmembrane domains. Except for the Nichols type strain, all rabbit-propagated isolates of T. pallidum examined thus far are comprised of mixed populations of organisms with heterogeneous tprK sequences. We show that tprK sequences in treponemes obtained directly from syphilis patients are also heterogeneous. Clustering analysis demonstrates that primary chancre tprK sequences are more likely to cluster within a sample than among samples and that tighter clustering is seen within chancre samples than within rabbit-propagated isolates. Closer analysis of tprK sequences from a rabbit-propagated isolate reveals that individual variable regions have different levels of diversity, suggesting that variable regions may have different intrinsic rates of sequence change or may be under different levels of selection. Most variable regions show increased sequence diversity upon passage. We speculate that the diversification of tprK during infection allows organisms to evade the host immune response, contributing to reinfection and persistent infection.

Amino Acid Sequence↗
PubMed2004

Genomic background predicts the fate of duplicated genes: evidence from the yeast genome.

Gene duplication with subsequent divergence plays a central role in the acquisition of genes with novel function and complexity during the course of evolution. With reduced functional constraints or through positive selection, these duplicated genes may experience accelerated evolution. Under the model of subfunctionalization, loss of subfunctions leads to complementary acceleration at sites with two copies, and the difference in average rate between the sequences may not be obvious. On the other hand, the classical model of neofunctionalization predicts that the evolutionary rate in one of the two duplicates is accelerated. However, the classical model does not tell which of the duplicates experiences the acceleration in evolutionary rate. Here, we present evidence from the Saccharomyces cerevisiae genome that a duplicate located in a genomic region with a low-recombination rate is likely to evolve faster than a duplicate in an area of high recombination. This observation is consistent with population genetics theory that predicts that purifying selection is less effective in genomic regions of low recombination (Hill-Robertson effect). Together with previous studies, our results suggest the genomic background (e.g., local recombination rate) as a potential force to drive the divergence between nontandemly duplicated genes. This implies the importance of structure and complexity of genomes in the diversification of organisms via gene duplications.

Evolution, Molecular↗
PubMed1997

Uncertainty considerations in group decisions: staffing and ratesetting in a health promotion center.

There are a variety of methods for including risk or uncertainty in Group Decision Support Systems (GDSS). Monte Carlo simulation is one method. An application of Monte Carlo simulation in Group Decisions and GDSS for diversification of services is presented in this paper. Specifically, the uncertainty associated with the finances of a Health Promotion Center are evaluated for staffing and rate setting. The distributions of outcome variables are used in decision rules.

Ambulatory Care Facilities↗
PubMed2001

Recombination within natural populations of pathogenic bacteria: short-term empirical estimates and long-term phylogenetic consequences.

The identification of clones within bacterial populations is often taken as evidence for a low rate of recombination, but the validity of this inference is rarely examined. We have used statistical tests of congruence between gene trees to examine the extent and significance of recombination in six bacterial pathogens. For Neisseria meningitidis, Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus, the congruence between the maximum likelihood trees reconstructed using seven house-keeping genes was in most cases no better than that between each tree and trees of random topology. The lack of congruence between gene trees in these four species, which include both naturally transformable and nontransformable species, is in three cases supported by high ratios of recombination to point mutation during clonal diversification (estimates of this parameter were not possible for Strep. pyogenes). In contrast, gene trees constructed for Hemophilus influenzae and pathogenic isolates of Escherichia coli showed a higher degree of congruence, suggesting lower rates of recombination. The impact of recombination therefore varies between bacterial species but in many species is sufficient to obliterate the phylogenetic signal in gene trees.

Alleles↗
PubMed2005

Phylogeography and demography of Guianan harlequin toads (Atelopus): diversification within a refuge.

We investigated the genetic structure of populations of Guianan harlequin toads (genus Atelopus) and their evolutionary affinities to extra-Guianan congeners. Phylogenetic analysis of mitochondrial cytochrome b (cyt b) and NADH dehydrogenase subunit 2 (ND2) gene sequences produced well-supported clades largely corresponding to the four recognized taxa in the Guianas (Atelopus spumarius hoogmoedi, Atelopus spumarius barbotini, Atelopus franciscus, and Atelopus flavescens). Our findings suggest that the Guianan A. spumarius represent distinct evolutionary lineages that merit distinction from Amazonian conspecifics, and that the status of A. flavescens and A. franciscus is somewhat less clear. Approximately 69% of the observed genetic variation is accounted for by differences between these four recognized taxa. Coalescent-based estimates of gene flow between taxa suggest that these lineages are largely isolated from one another. Negligible rates of migration between populations and significant divergence within such close proximity suggests that although the region inhabited by these taxa is almost entirely undisturbed, significant habitat heterogeneity exists as to have produced a remarkable diversification of Atelopus within the eastern Guiana Shield. These results contradict the commonly held view of the Guiana Shield as a 'refuge' whose stability during late Tertiary and Quaternary climatic fluctuations served as a biotic reservoir. Instead, we provide evidence that climatic fluctuations during this time had a diversifying effect within the Guianan region.

Animals↗
PubMed2002

Horizontal gene transfer and bacterial diversity.

Bacterial genomes are extremely dynamic and mosaic in nature. A substantial amount of genetic information is inserted into or deleted from such genomes through the process of horizontal transfer. Through the introduction of novel physiological traits from distantly related organisms, horizontal gene transfer often causes drastic changes in the ecological and pathogenic character of bacterial species and thereby promotes microbial diversification and speciation. This review discusses how the recent influx of complete chromosomal sequences of various microorganisms has allowed for a quantitative assessment of the scope, rate and impact of horizontally transmitted information on microbial evolution.

Animals↗
PubMed2004

Chemical conversion of alpha-keto acids in relation to flavor formation in fermented foods.

Formation of flavor compounds from branched-chain alpha-keto acids in fermented foods such as cheese is believed to be mainly an enzymatic process, while the conversion of phenyl pyruvic acid, which is derived from phenylalanine, also proceeds chemically. In this research, the chemical conversion of alpha-keto acids to aldehydes with strong flavor characteristics was studied, with the main focus on the conversion of alpha-ketoisocaproic acid to the aldehyde 2-methylpropanal, and a manganese-catalyzed reaction mechanism is proposed for this conversion. The mechanism involves keto-enol tautomerism, enabling molecular oxygen to react with the beta-carbon atom of the alpha-keto acid, resulting in a peroxide. This peroxide can react in several ways, leading to unstable dioxylactone or noncyclic intermediates. These intermediates will break down into an aldehyde and oxalate or carbon oxides (CO and CO(2)). All the alpha-keto acids tested were converted at pH 5.5 and in the presence of manganese, although their conversion rates were rather diverse. This chemical reaction might provide new ways for controlling cheese flavor formation with the aim of acceleration of the ripening process or diversification of the flavor characteristics.

Aldehydes↗
PubMed2000

Both subunits of the dimeric plant photoreceptor phytochrome require chromophore for stability of the far-red light-absorbing form.

The dimeric plant photoreceptor phytochrome is converted from its inactive red light-absorbing form (Pr) into the active far-red light-absorbing form (Pfr) upon light absorption. Dynamics of Pfr generation and of thermal Pfr-to-Pr conversion are of fundamental importance for inducing adequate responses to light signals. Here, we analyzed the role of subunit interactions on spectroscopic properties of dimeric phytochrome A. Using a coexpression system and affinity chromatography, we prepared mixed phytochrome dimers that can incorporate the essential chromophore only in one subunit. We demonstrate that such mixed dimers have unaltered difference spectra. In contrast, dark reversion differed greatly between Pfr-Pfr homodimers and Pfr-Pr heterodimers, the former being about 100-fold more stable. Temperature dependence of reaction rates revealed an additional stabilization of about 4 kcal/mol in homodimers. Consequences of these findings are discussed in relation to the biological function of, and functional diversification between, phytochrome family members.

Absorption↗
PubMed2002

Power of eight tree shape statistics to detect nonrandom diversification: a comparison by simulation of two models of cladogenesis.

We used simulations to compare the relative power of eight statistical tests to detect imbalance in phylogenies that is too great to be ascribed to an equal-rates Markov null model. Three of these tests have never had their power assessed before. Our simulations are the first to assess performance under scenarios in which the speciation rates of various lineages can evolve independently. In one of the scenarios explored, rates depend upon the value of an evolving trait, whereas in the other the probability that a species will speciate declines with the time since it last did so. The results indicate that the relative performance of the methods depends upon how the imbalance is generated. Different types of processes lead to different imbalance signatures, i.e., different patterns of imbalance at different depths in the phylogeny, and the measures of tree shape differ in the depth of phylogeny at which they are most sensitive. Relative performance is also affected by tree size but does not appear to depend greatly upon the degree of speciation rate variation among lineages. Two of the indices (Colless's index I(c) and Shao and Sokal's Nmacr;) show reasonable performance throughout, but another (Shao and Sokal's B(2)) is never indicated to be a preferred method. Two tests that do not require completely resolved phylogenies, mean I' and mean I'(10), have reasonable power.

Biological Evolution↗
PubMed1997

Ethnic diversification in clinical psychology graduate training.

Thirty-eight directors and 334 advanced graduate students from clinical psychology programs completed a survey on ethnic minority training offered in clinical doctoral programs. Comparisons were made between directors' and students' ratings on the following variables: students' level of interest in ethnic minority training, the importance of this training, and the effectiveness of the clinical programs' minority-related education. Minority and nonminority students' responses were also compared on these variables. Supplementary data were collected on ethnic minority education in coursework, research, and clinical practica. Findings indicate that students, relative to clinical directors, assign more importance to ethnic minority training and lower efficacy ratings to their programs' ethnic minority education. The results also suggest that minority students feel more strongly about the value of ethnic minority training than do their nonminority peers and the directors. The implications of these results are discussed, and recommendations are made to address identified problems.

Attitude of Health Personnel↗
PubMed2002

Evolutionary shifts between host oak sections and host-plant organs in Andricus gallwasps.

Gall-inducing insects have especially intimate interactions with their host plants and generally show great specificity with regard to both the host-plant species and the organ (e.g. flower, leaf) galled. However, the relative roles of shifts between host species and between host-plant organs in the diversification of gall-inducers are uncertain. We employ a novel and general maximum-likelihood approach to show that shifts between host-plant organs occur at a significantly greater rate than shifts between host oak sections in European Andricus gallwasps. This suggests that speciation has more often been associated with gall location shifts than with colonization of new host-plant species, and implies that it may be easier for gall-inducers to colonize new plant organs than new plant species. Andricus gallwasps have complex life cycles, with obligate alternation of sexual and parthenogenetic generations. Our phylogenetic analyses show that a life cycle with both generations galling white oaks (section Quercus) is ancestral, with a single shift of the sexual generation onto black oaks (section Cerris) to generate a clade with a novel host-alternating life cycle. This new life cycle provided the opportunity for further speciation, but may have also increased the risk of extinction of one or both generations by the demographic requirement for co-existence of both host-plant groups. In summary, it appears that Andricus gallwasp radiation may be a two-level process. Speciation events often involve shifts in gall location on the same host species. However, there are only so many ways to gall an oak, and rare shifts to new oak sections may contribute greatly to long-term diversification by opening up whole new adaptive zones.

Adaptation, Physiological↗
PubMed1997

Increase of spontaneous intrachromosomal homologous recombination in mammalian cells expressing a mutant p53 protein.

Homologous recombination plays an essential role in processes involved in genome stability/instability, such as molecular evolution, gene diversification, meiotic chromosome segregation, DNA repair and chromosomal rearrangements. p53 devoid cells exhibit predisposition to neoplasia, defects in G1 checkpoint and high genetic instability but a normal rate of point mutations. We investigated the effect of a p53 mutation, on spontaneous homologous recombination between intrachromosomal direct repeat sequences, in mouse L cells. In these cells, wild type for the p53 gene, we have overexpressed the mutant p53(175(Arg>His)) protein leading to a p53 mutant phenotype, as verified by the absence of a G1 arrest after gamma-irradiation. We show that the rate of spontaneous recombination is increased from five- to 20-fold in the mutant p53 lines. Moreover, this increase is observed in gene conversion as well as in deletion events. Our results provide new insights into the molecular mechanisms of genetic instability due to a defect of p53.

Animals↗
PubMed2002

Combined nuclear and mitochondrial DNA sequences resolve generic relationships within the Cracidae (Galliformes, Aves).

The Cracidae is one of the most endangered and distinctive bird families in the Neotropics, yet the higher relationships among taxa remain uncertain. The molecular phylogeny of its 11 genera was inferred using 10,678 analyzable sites (5,412 from seven different mitochondrial segments and 5,266 sites from four nuclear genes). We performed combinability tests to check conflicts in phylogenetic signals of separate genes and genomes. Phylogenetic analysis showed that the unrooted tree of ((curassows, horned guan) (guans, chachalacas)) was favored by most data partitions and that different data partitions provided support for different parts of the tree. In particular, the concatenated mitochondrial DNA (mtDNA) genes resolved shallower nodes, whereas the combined nuclear sequences resolved the basal connections among the major clades of curassows, horned guan, chachalacas, and guans. Therefore, we decided that for the Cracidae all data should be combined for phylogenetic analysis. Maximum parsimony (MP), maximum likelihood (ML), and Bayesian analyses of this large data set produced similar trees. The MP tree indicated that guans are the sister group to (horned guan, (curassows, chachalacas)), whereas the ML and Bayesian analysis recovered a tree where the horned guan is a sister clade to curassows, and these two clades had the chachalacas as a sister group. Parametric bootstrapping showed that alternative trees previously proposed for the cracid genera are significantly less likely than our estimate of their relationships. A likelihood ratio test of the hypothesis of a molecular clock for cracid mtDNA sequences using the optimal ML topology did not reject rate constancy of substitutions through time. We estimated cracids to have originated between 64 and 90 million years ago (MYA), with a mean estimate of 76 MYA. Diversification of the genera occurred approximately 41-3 MYA, corresponding with periods of global climate change and other Earth history events that likely promoted divergences of higher level taxa.

Animals↗
PubMed2001

Evolution of the angiosperms: calibrating the family tree.

Growing evidence of morphological diversity in angiosperm flowers, seeds and pollen from the mid Cretaceous and the presence of derived lineages from increasingly older geological deposits both imply that the timing of early angiosperm cladogenesis is older than fossil-based estimates have indicated. An alternative to fossils for calibrating the phylogeny comes from divergence in DNA sequence data. Here, angiosperm divergence times are estimated using non-parametric rate smoothing and a three-gene dataset covering ca. 75% of all angiosperm families recognized in recent classifications. The results provide an initial hypothesis of angiosperm diversification times. Using an internal calibration point, an independent evaluation of angiosperm and eudicot origins is performed. The origin of the crown group of extant angiosperms is indicated to be Early to Middle Jurassic (179-158 Myr), and the origin of eudicots is resolved as Late Jurassic to mid Cretaceous (147-131 Myr). Both estimates, despite a conservative calibration point, are older than current fossil-based estimates.

Calibration↗
PubMed2004

Ancient lakes as evolutionary reservoirs: evidence from the thalassoid gastropods of Lake Tanganyika.

Ancient lakes are often collectively viewed as evolutionary hot spots of diversification. East Africa's Lake Tanganyika has long been the subject of scientific interest owing to dramatic levels of endemism in species as diverse as cichlid fishes, paludomid gastropods, decapod and ostracod crustaceans and poriferans. It is the largest and deepest of the African rift lakes, and its endemic fauna has been presented with a stable inland environment for over 10 Myr, offering unique opportunities for within-lake diversification. Although astonishing diversification has been documented in the endemic cichlid fauna of the lake, similar patterns of rapid diversification have long been assumed for other groups. In contrast to this hypothesis of rapid speciation, we show here that there has been no acceleration in the rate of speciation in the thalassoid gastropods of the lake following lake colonization. While limited within-lake speciation has occurred, the dramatic conchological diversity of gastropods presently found within the lake has evolved from at least four major lineages that pre-date its formation by as much as 40 Myr. At the same time, a widespread group of African gastropods appears to have evolved from taxa presently found in the lake. While Lake Tanganyika has been a cradle of speciation for cichlid fishes, it has also been an important evolutionary reservoir of gastropod lineages that have been extirpated outside the basin.

Animals↗
PubMed1996

A newly identified immunodominant membrane protein (pMB67) involved in Mycoplasma bovis surface antigenic variation.

Mycoplasma bovis is a bovine pathogen able to cause systemic disease. It possesses a series of prominent, structurally related yet clearly distinguishable membrane lipoproteins on the cell surface. These variable surface proteins (Vsps) undergo highly dynamic and spontaneous changes in size and expression and are key immunogenic components. They may play a critical role as mediators of adherence to host cells and in escaping immune destruction. In this report, we define a novel, Vsp-unrelated membrane protein also associated with M. bovis surface antigenic variation. This protein has an apparent molecular mass of 67,000 Da in the type strain PG45 and was designated pMB67. Immunological and biochemical characterization of pMB67 demonstrated that it: (i) contains a specific epitope, (ii) is not modified by lipid but does contain cysteine, (iii) does not contain a Vsp-like repetitive periodic protein structure, (iv) is a predominant antigen recognized during M. bovis infections, (v) undergoes a high rate of phase variation in vitro and (vi) is size-variable. These results showed that M. bovis employs two types of specialized membrane proteins for surface diversification. The pMB67 protein may be useful in diagnostic assays and as a vaccine component.

Animals↗
PubMed2005

Back where we belong.

If you were the CEO of Pitney Bowes, the postage meter maker, how would you envision the future of the business? The company has an undeniable core competence in the solutions it provides to high-volume postal service users. But with snail mail on the decline, some would say that core has about as much future as the buggy whip. In this article, Pitney Bowes chairman and CEO Michael Critelli gives us a glimpse of how he leads his company's strategy development--and how that development has supported a counterintuitive return to the company's core after decades of diversification. He and others in the company begin the process by tapping into deeply knowledgeable people and organizations to understand key trends in the business and the rate at which change is occurring. Then, it's a question of the firm reshaping the environment in which it does business, whether through R&D investments or work with regulators and policy makers who influence market forces; this is especially important in emerging markets. Focusing on a core business area enables a company to find adjacent high-margin opportunities and to offer comprehensive solutions to customers. What stands out most sharply in this account, however, is the importance of having a strategist's mind-set. Whether Critelli is reading the day's news, visiting a key account, or spending an hour with his own people working in the context of a customer mail room, he is constantly extrapolating possible long-term competitive implications from the immediate facts. Often inspired by strategic thinkers, Critelli believes that the greatest thing he can do for his organization is to shift the terms of the debate. "Rarely am I credited with sterling words or bold, symbolic actions", he writes. "Instead, I help people to see the business we are in differently and to reach a shared vision as to where we want to end up. And, little by little, things move in the right direction".

Administrative Personnel↗
PubMed2003

Placental mammal diversification and the Cretaceous-Tertiary boundary.

Competing hypotheses for the timing of the placental mammal radiation focus on whether extant placental orders originated and diversified before or after the Cretaceous-Tertiary (KT) boundary. Molecular studies that have addressed this issue suffer from single calibration points, unwarranted assumptions about the molecular clock, andor taxon sampling that lacks representatives of all placental orders. We investigated this problem using the largest available molecular data set for placental mammals, which includes segments of 19 nuclear and three mitochondrial genes for representatives of all extant placental orders. We used the ThorneKishino method, which permits simultaneous constraints from the fossil record and allows rates of molecular evolution to vary on different branches of a phylogenetic tree. Analyses that used different sets of fossil constraints, different priors for the base of Placentalia, and different data partitions all support interordinal divergences in the Cretaceous followed by intraordinal diversification mostly after the KT boundary. Four placental orders show intraordinal diversification that predates the KT boundary, but only by an average of 10 million years. In contrast to some molecular studies that date the rat-mouse split as old as 46 million years, our results show improved agreement with the fossil record and place this split at 16-23 million years. To test the hypothesis that molecular estimates of Cretaceous divergence times are an artifact of increased body size subsequent to the KT boundary, we also performed analyses with a "KT body size" taxon set. In these analyses, interordinal splits remained in the Cretaceous.

Animals↗