Summary: The program MODELTEST uses log likelihood scores to establish the model of DNA evolution that best fits the data. Availability: The MODELTEST package, including the source code and some documentation is available at http://bioag.byu.edu/zoology/crandall―lab/modeltest.html. Contact: dp47@email.byu.edu.

/pdf/modeltest-testing-the-model-of-dna-substitution-2dmippvvyz.pdf

MODELTEST: testing the model of DNA substitution.

PhyML is a phylogeny software based on the maximum-likelihood principle. Early PhyML versions used a fast algorithm performing nearest neighbor interchanges to improve a reasonable starting tree topology. Since the original publication (Guindon S., Gascuel O. 2003. A simple, fast and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst. Biol. 52:696-704), PhyML has been widely used (>2500 citations in ISI Web of Science) because of its simplicity and a fair compromise between accuracy and speed. In the meantime, research around PhyML has continued, and this article describes the new algorithms and methods implemented in the program. First, we introduce a new algorithm to search the tree space with user-defined intensity using subtree pruning and regrafting topological moves. The parsimony criterion is used here to filter out the least promising topology modifications with respect to the likelihood function. The analysis of a large collection of real nucleotide and amino acid data sets of various sizes demonstrates the good performance of this method. Second, we describe a new test to assess the support of the data for internal branches of a phylogeny. This approach extends the recently proposed approximate likelihood-ratio test and relies on a nonparametric, Shimodaira-Hasegawa-like procedure. A detailed analysis of real alignments sheds light on the links between this new approach and the more classical nonparametric bootstrap method. Overall, our tests show that the last version (3.0) of PhyML is fast, accurate, stable, and ready to use. A Web server and binary files are available from http://www.atgc-montpellier.fr/phyml/.

https://www.zora.uzh.ch/id/eprint/155669/1/ZORA_NL_155669.pdf

New Algorithms and Methods to Estimate Maximum-Likelihood Phylogenies: Assessing the Performance of PhyML 3.0

A set of oligonucleotide primers capable of initiating enzymatic amplification (polymerase chain reaction) on a phylogenetically and taxonomically wide range of bacteria is described along with methods for their use and examples. One pair of primers is capable of amplifying nearly full-length 16S ribosomal DNA (rDNA) from many bacterial genera; the additional primers are useful for various exceptional sequences. Methods for purification of amplified material, direct sequencing, cloning, sequencing, and transcription are outlined. An obligate intracellular parasite of bovine erythrocytes, Anaplasma marginale, is used as an example; its 16S rDNA was amplified, cloned, sequenced, and phylogenetically placed. Anaplasmas are related to the genera Rickettsia and Ehrlichia. In addition, 16S rDNAs from several species were readily amplified from material found in lyophilized ampoules from the American Type Culture Collection. By use of this method, the phylogenetic study of extremely fastidious or highly pathogenic bacterial species can be carried out without the need to culture them. In theory, any gene segment for which polymerase chain reaction primer design is possible can be derived from a readily obtainable lyophilized bacterial culture.

16S ribosomal DNA amplification for phylogenetic study.

jModelTest is a new program for the statistical selection of models of nucleotide substitution based on "Phyml" (Guindon and Gascuel 2003. A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol. 52:696-704.). It implements 5 different selection strategies, including "hierarchical and dynamical likelihood ratio tests," the "Akaike information criterion," the "Bayesian information criterion," and a "decision-theoretic performance-based" approach. This program also calculates the relative importance and model-averaged estimates of substitution parameters, including a model-averaged estimate of the phylogeny. jModelTest is written in Java and runs under Mac OSX, Windows, and Unix systems with a Java Runtime Environment installed. The program, including documentation, can be freely downloaded from the software section at http://darwin.uvigo.es.

/pdf/jmodeltest-phylogenetic-model-averaging-4hpp3p5d0f.pdf

jModelTest: Phylogenetic Model Averaging

Motivation: In 2001 and 2002, we published two papers (Bioinformatics, 17, 282--283, Bioinformatics, 18, 77--82) describing an ultrafast protein sequence clustering program called cd-hit. This program can efficiently cluster a huge protein database with millions of sequences. However, the applications of the underlying algorithm are not limited to only protein sequences clustering, here we present several new programs using the same algorithm including cd-hit-2d, cd-hit-est and cd-hit-est-2d. Cd-hit-2d compares two protein datasets and reports similar matches between them; cd-hit-est clusters a DNA/RNA sequence database and cd-hit-est-2d compares two nucleotide datasets. All these programs can handle huge datasets with millions of sequences and can be hundreds of times faster than methods based on the popular sequence comparison and database search tools, such as BLAST.

Availability: http://cd-hit.org

Contact: [email protected]

Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences

Previous data revealed that a variety of mouse fetal tissues, with the exception of the placenta, are capable of producing IGF-I that may act locally to regulate fetal growth (D'Ercole, et al.,Dev. Biol. 75: 315, 1980). Although the placenta is essential for normal fetal development, little is known regarding the mechanisms controlling placental growth. Human placental explants were examined at various stages of gestation for the ability to produce IGF-I in organ culture. The placental explants were washed extensively and incubated in serum-free media. The media was acidified and chromatographed over a Sephadex G-50 column to separate the IGF-I from specific binding proteins. IGF-I was measured by specific radioimmunoassay (RIA). Placental tissue from all gestational ages secreted immunoreactive IGF-I, 2.19±.35 ng./mg. prot./48 hrs. (Mean±S.D.). There was no difference in IGF-I production between pre-term (9-19wk.) and term placentae under these conditions. The activity was reduced >60% by 50 uM cyclohexamide, suggesting that most of the activity was the result of de novo protein synthesis. The similarity of this material to authentic human IGF-I is supported by parallel displacement in the RIA and co-elution on a Sephadex G-50 column. The human placenta contains specific IGF receptors. These data demonstrate that the human placenta is also capable of producing IGF-I, that may act locally to regulate placental growth.

/pdf/production-of-insulin-like-growth-factor-i-igf-i-by-human-1zdmw06a67.pdf

Production of insulin-like growth factor-i (igf-i) by human placental tissue

Leukocytes are among the few cells of human origin that can be relatively easily obtained from the living subject. For this reason, they have been periodically used to measure the tissue status of enzymes, metabolites, and essential nutrients such as vitamin C. Some years ago, Metcoff and his colleagues1,2 related changes in the energy metabolism of leukocytes to the degree of postnatal malnutrition of young children. They were able to demonstrate a deficit in the capacity for generation of adenosine triphosphate (ATP) in the leukocytes of infants with protein-calorie malnutrition and correlated this with reduced activities of the enzymes pyruvate kinase and adenylate kinase which are involved in the metabolism of ATP formed by glycolysis, the predominating energy-generating process in leukocytes.

Leukocytes and fetal malnutrition.

The preceding two papers in this series describe the regulation of protein metabolism in man (MUNRO 1974a) and the impact of food intake on his protein metabolism (MUNRO 1974b). This final paper deals with the effects of some important disease processes, notably infection and injury, on protein metabolism, and the nutritional implications of these changes. Acute infections, injury and many other diseases give rise to loss of body protein, and, in consequence, protein from the diet must be retained in order to restore the body to its previous state. Some of these conditions, such as non-specific stresses, respiratory infections, and temporary gastrointestinal infections are so common that the amounts of protein needed to restore the protein content of the body could be regarded as a requirement of everyday living. Other conditions, such as fractures, burns and liver damage may not occur to an individual during his whole lifetime, and dietary treatment during the course of such illnesses is part of the therapy administered by the physician or surgeon, and can be a major factor in survival requiring special measures such as parenteral nutrition. The clinical recognition of undernutrition can be demanding; for example, SHINABERGER & GINA (1968) describe patients on renal dialysis who were unable to maintain their serum albumin levels on an otherwise adequate intake of protein (0.75 g/kg) when they suffered an infection, operation, etc. The authors comment that “this level of protein intake permits no nutritional reserve capacity to buffer a catabolic state”.

Hamish N. Munro

Papers

Production of insulin-like growth factor-i (igf-i) by human placental tissue

Leukocytes and fetal malnutrition.

Protein metabolism in response to injury and other pathological conditions.

Evolving scientific bases for the Recommended Dietary Allowances--a critical look at methodologies.

Nutrition and aging: the challenge