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At least 757 records · Page 42Linked to original sources
PubMed2001

The rhythm of microbial adaptation.

The evolutionary biologist "studies the steps by which the miraculous adaptations so characteristic of every aspect of the organic world have evolved". But the general nature of such adaptive steps is still unclear. Evolution is often thought to be random and dependent on unpredictable events. In this light, one might expect the steps taken by adaptation to be completely random, both biologically and temporally. Here I present a mathematical derivation to show that, on the contrary, adaptive steps can have fairly strong rhythm. I find that the strength of the adaptive rhythm, that is its relative temporal regularity, is equal to a constant that is the same for all microbial populations. As a consequence, numbers of accumulated adaptations are predicted to have a universal variance/mean ratio. The theory derived here is potentially applicable to the study of molecular evolution.

Adaptation, Physiological↗
PubMed2001

An evolutionarily conserved motif in the TAB1 C-terminal region is necessary for interaction with and activation of TAK1 MAPKKK.

TAK1, a member of the MAPKKK family, is involved in the intracellular signaling pathways mediated by transforming growth factor beta, interleukin 1, and Wnt. TAK1 kinase activity is specifically activated by the TAK1-binding protein TAB1. The C-terminal 68-amino acid sequence of TAB1 (TAB1-C68) is sufficient for TAK1 interaction and activation. Analysis of various truncated versions of TAB1-C68 defined a C-terminal 30-amino acid sequence (TAB1-C30) necessary for TAK1 binding and activation. NMR studies revealed that the TAB1-C30 region has a unique alpha-helical structure. We identified a conserved sequence motif, PYVDXA/TXF, in the C-terminal domain of mammalian TAB1, Xenopus TAB1, and its Caenorhabditis elegans homolog TAP-1, suggesting that this motif constitutes a specific TAK1 docking site. Alanine substitution mutagenesis showed that TAB1 Phe-484, located in the conserved motif, is crucial for TAK1 binding and activation. The C. elegans homolog of TAB1, TAP-1, was able to interact with and activate the C. elegans homolog of TAK1, MOM-4. However, the site in TAP-1 corresponding to Phe-484 of TAB1 is an alanine residue (Ala-364), and changing this residue to Phe abrogates the ability of TAP-1 to interact with and activate MOM-4. These results suggest that the Phe or Ala residue within the conserved motif of the TAB1-related proteins is important for interaction with and activation of specific TAK1 MAPKKK family members in vivo.

Amino Acid Motifs↗
PubMed2001

Evolution and current use of the tuberculin test.

Since it was first introduced in the late 1800s, the tuberculin test has undergone continual refinement in its formulation, standardization, and dosage, as well as its interpretation and indications for use. New guidelines have replaced universal screening with targeted testing and rigid definitions of positivity with individualized criteria formulated from a Bayesian approach. This review summarizes the evolution of the test and provides information to help gauge its predictive value.

Animals↗
PubMed2004

Antiretroviral therapy and the clinical evolution of human papillomavirus-associated genital lesions in HIV-positive women.

The effect of antiretroviral therapy on the natural history of human papillomavirus (HPV)-associated genital lesions was evaluated in 201 human immunodeficiency virus (HIV)-infected women who were followed-up for 1-6 years. Gynecologic examinations were performed every 6-12 months. HPV sequences in cervico-vaginal cells, analyzed by polymerase chain reaction and typed by restriction fragment-length polymorphism analysis, were repeatedly detected in 126 women; 29 had transient HPV infection. Genital lesions were found in 137 patients; prevalence was comparable in women who were receiving different antiretroviral regimens. Regression of low-grade lesions was more prevalent among patients receiving highly active antiretroviral therapy than among those receiving other regimens; high-grade lesions regressed in the majority of cases, regardless of antiretroviral therapy. HPV infection persisted in nearly 80% of the cases. In conclusion, our data show that antiretroviral therapy does not prevent the development of HPV-associated lesions and does not eliminate HPV infection; therefore, early and strict gynecologic follow-up of HIV-infected women is warranted.

Adult↗
PubMed2004

A link between SIVsm in sooty mangabeys (SM) in wild-living monkeys in Sierra Leone and SIVsm in an American-based SM colony.

We have developed a noninvasive method for SIVsm virion RNA detection in feces of captive sooty mangabeys (SMs) (Cercocebus atys). Employing this method to investigate the natural history of SIVsm in endangered SMs is useful for understanding the diversity and evolution of SIVsm and HIV-2. The fecal samples of 61 wild-living SMs and 14 chimpanzees (Pan troglodytes verus) were studied. Samples were collected in rural Sierra Leone in 1993. One SM sample tested positive by reverse transcriptase-PCR. No viral sequence was detected in the feces of 14 chimpanzees. Phylogenetic analysis of the env sequence obtained from SM#13 showed that it clustered within the SIVsm lineage that includes SIVsmH4, B670, and PBj, confirming a direct connection between SIVsm from West Africa and an American-based colony of SM. The virus, designated as SIVsmSL93g, supports a link between the SIVB670/SIVsmH4/SIVPbj lineage and SMs living in Northern Sierra Leone in 1993. The discovery of this strain in a wild-living SM also indicates that noninvasive methods can be used for SIV detection from monkey feces collected in the field.

Animals↗
PubMed2002

A viral sampling design for testing the molecular clock and for estimating evolutionary rates and divergence times.

MOTIVATION: The high pace of viral sequence change means that variation in the times at which sequences are sampled can have a profound effect both on the ability to detect trends over time in evolutionary rates and on the power to reject the Molecular Clock Hypothesis (MCH). Trends in viral evolutionary rates are of particular interest because their detection may allow connections to be established between a patient's treatment or condition and the process of evolution. Variation in sequence isolation times also impacts the uncertainty associated with estimates of divergence times and evolutionary rates. Variation in isolation times can be intentionally adjusted to increase the power of hypothesis tests and to reduce the uncertainty of evolutionary parameter estimates, but this fact has received little previous attention. RESULTS: We provide approximations for the power to reject the MCH when the alternative is that rates change in a linear fashion over time and when the alternative is that rates differ randomly among branches. In addition, we approximate the standard deviation of estimated evolutionary rates and divergence times. We illustrate how these approximations can be exploited to determine which viral sample to sequence when samples representing different dates are available.

Computational Biology↗
PubMed2005

Selecton: a server for detecting evolutionary forces at a single amino-acid site.

UNLABELLED: We present an algorithmic tool for the identification of biologically significant amino acids in proteins of known three dimensional structure. We estimate the degree of purifying selection and positive Darwinian selection at each site and project these estimates onto the molecular surface of the protein. Thus, patches of functional residues (undergoing either positive or purifying selection), which may be discontinuous in the linear sequence, are revealed. We test for the statistical significance of the site-specific scores in order to obtain reliable and valid estimates. AVAILABILITY: The Selecton web server is available at: http://selecton.bioinfo.tau.ac.il SUPPLEMENTARY INFORMATION: More information is available at http://selecton.bioinfo.tau.ac.il/overview.html. A set of examples is available at http://selecton.bioinfo.tau.ac.il/gallery.html.

Algorithms↗
PubMed1996

Historical perspectives on the evolution in understanding the importance of nutritional care in pediatric HIV infection.

Women, perinatally-infected infants, and sexually exposed and exploited youths and adolescents have become a major focus of the worldwide HIV/AIDS pandemic. Increased perinatal screening, improvement in early infant diagnosis, and the benefits of primary HIV therapies have increased the numbers identified and longevity of infants and children living with HIV. This increase in survival is associated with HIV/AIDS becoming a chronic multiorgan system disease that requires a multidiscipline comprehensive care approach. The combination of poor oral intake, increased loss, and increased metabolic needs of long-term surviving HIV-infected children are obstacles to both survival and quality of life. HIV-infected children and their families need supportive care services including nutritional as well as primary therapy. Clinical guidelines for effective nutrition interventions must be developed to prevent and treat failure to thrive and wasting syndrome. Gains in survival duration must be linked to enhanced quality of life through supportive care, including comprehensive nutritional services that have their efficacy documented by appropriate clinical trials.

Adolescent↗
PubMed2006

Automated phylogenetic detection of recombination using a genetic algorithm.

The evolution of homologous sequences affected by recombination or gene conversion cannot be adequately explained by a single phylogenetic tree. Many tree-based methods for sequence analysis, for example, those used for detecting sites evolving nonneutrally, have been shown to fail if such phylogenetic incongruity is ignored. However, it may be possible to propose several phylogenies that can correctly model the evolution of nonrecombinant fragments. We propose a model-based framework that uses a genetic algorithm to search a multiple-sequence alignment for putative recombination break points, quantifies the level of support for their locations, and identifies sequences or clades involved in putative recombination events. The software implementation can be run quickly and efficiently in a distributed computing environment, and various components of the methods can be chosen for computational expediency or statistical rigor. We evaluate the performance of the new method on simulated alignments and on an array of published benchmark data sets. Finally, we demonstrate that prescreening alignments with our method allows one to analyze recombinant sequences for positive selection.

Algorithms↗
PubMed2006

Evolutionary model selection with a genetic algorithm: a case study using stem RNA.

The choice of a probabilistic model to describe sequence evolution can and should be justified. Underfitting the data through the use of overly simplistic models may miss out on interesting phenomena and lead to incorrect inferences. Overfitting the data with models that are too complex may ascribe biological meaning to statistical artifacts and result in falsely significant findings. We describe a likelihood-based approach for evolutionary model selection. The procedure employs a genetic algorithm (GA) to quickly explore a combinatorially large set of all possible time-reversible Markov models with a fixed number of substitution rates. When applied to stem RNA data subject to well-understood evolutionary forces, the models found by the GA 1) capture the expected overall rate patterns a priori; 2) fit the data better than the best available models based on a priori assumptions, suggesting subtle substitution patterns not previously recognized; 3) cannot be rejected in favor of the general reversible model, implying that the evolution of stem RNA sequences can be explained well with only a few substitution rate parameters; and 4) perform well on simulated data, both in terms of goodness of fit and the ability to estimate evolutionary rates. We also investigate the utility of several distance measures for comparing and contrasting inferred evolutionary models. Using widely available small computer clusters, our approach allows, for the first time, to evaluate the performance of existing RNA evolutionary models by comparing them with a large pool of candidate models and to validate common modeling assumptions. In addition, the new method provides the foundation for rigorous selection and comparison of substitution models for other types of sequence data.

Algorithms↗
PubMed1999

A method for detecting positive selection at single amino acid sites.

A method was developed for detecting the selective force at single amino acid sites given a multiple alignment of protein-coding sequences. The phylogenetic tree was reconstructed using the number of synonymous substitutions. Then, the neutrality was tested for each codon site using the numbers of synonymous and nonsynonymous changes throughout the phylogenetic tree. Computer simulation showed that this method accurately estimated the numbers of synonymous and nonsynonymous substitutions per site, as long as the substitution number on each branch was relatively small. The false-positive rate for detecting the selective force was generally low. On the other hand, the true-positive rate for detecting the selective force depended on the parameter values. Within the range of parameter values used in the simulation, the true-positive rate increased as the strength of the selective force and the total branch length (namely the total number of synonymous substitutions per site) in the phylogenetic tree increased. In particular, with the relative rate of nonsynonymous substitutions to synonymous substitutions being 5.0, most of the positively selected codon sites were correctly detected when the total branch length in the phylogenetic tree was > or = 2.5. When this method was applied to the human leukocyte antigen (HLA) gene, which included antigen recognition sites (ARSs), positive selection was detected mainly on ARSs. This finding confirmed the effectiveness of the present method with actual data. Moreover, two amino acid sites were newly identified as positively selected in non-ARSs. The three-dimensional structure of the HLA molecule indicated that these sites might be involved in antigen recognition. Positively selected amino acid sites were also identified in the envelope protein of human immunodeficiency virus and the influenza virus hemagglutinin protein. This method may be helpful for predicting functions of amino acid sites in proteins, especially in the present situation, in which sequence data are accumulating at an enormous speed.

Amino Acid Substitution↗
PubMed2000

Reconstructing genealogies of serial samples under the assumption of a molecular clock using serial-sample UPGMA.

Reconstruction of evolutionary relationships from noncontemporaneous molecular samples provides a new challenge for phylogenetic reconstruction methods. With recent biotechnological advances there has been an increase in molecular sequencing throughput, and the potential to obtain serial samples of sequences from populations, including rapidly evolving pathogens, is fast being realized. A new method called the serial-sample unweighted pair grouping method with arithmetic means (sUPGMA) is presented that reconstructs a genealogy or phylogeny of sequences sampled serially in time using a matrix of pairwise distances. The resulting tree depicts the terminal lineages of each sample ending at a different level consistent with the sample's temporal order. Since sUPGMA is a variant of UPGMA, it will perform best when sequences have evolved at a constant rate (i.e., according to a molecular clock). On simulated data, this new method performs better than standard cluster analysis under a variety of longitudinal sampling strategies. Serial-sample UPGMA is particularly useful for analysis of longitudinal samples of viruses and bacteria, as well as ancient DNA samples, with the minimal requirement that samples of sequences be ordered in time.

DNA, Viral↗
PubMed2002

What can modeling tell us about the threat of antiviral drug resistance?

PURPOSE OF REVIEW: Currently, antiviral resistance is a major public health concern. Here, we review how mathematical models have been used to provide insights into the emerging threat of antiviral resistance. We focus mainly on the problem of drug resistance to HIV. RECENT FINDINGS: We review how antiviral models of HIV have been used: (1) to understand the evolution of an epidemic of drug-resistant HIV, (2) to predict the incidence and prevalence of drug-resistant HIV, (3) to conduct biological 'cost-benefit' analyses, and(4) to make public health policy recommendations. We also briefly discuss antiviral resistance for HSV-2 and influenza. Recent studies indicate that for HSV-2 and influenza drug resistance is not likely to become a major public health problem. However, for HIV the situation is very different. Results from several studies predict that a high prevalence of drug-resistant HIV will be an inevitable consequence of more widespread usage of antiretroviral therapies (ART). However more widespread usage of ART will save a substantial number of lives, and could even result in epidemic eradication. SUMMARY: Models have been used in many ways to provide insight into the emerging threat of antiviral resistance, particularly for HIV. At this stage in the HIV epidemic the most important future use of models may be that they will force the goals of public health policies to be clearly defined. Once goals have been defined it can then be decided whether a high prevalence of drug-resistant HIV is a threat or simply a justified means to an end.

Anti-HIV Agents↗