The increase in the number of large data sets and the complexity of current probabilistic sequence evolution models necessitates fast and reliable phylogeny reconstruction methods. We describe a new approach, based on the maximum- likelihood principle, which clearly satisfies these requirements. The core of this method is a simple hill-climbing algorithm that adjusts tree topology and branch lengths simultaneously. This algorithm starts from an initial tree built by a fast distance-based method and modifies this tree to improve its likelihood at each iteration. Due to this simultaneous adjustment of the topology and branch lengths, only a few iterations are sufficient to reach an optimum. We used extensive and realistic computer simulations to show that the topological accuracy of this new method is at least as high as that of the existing maximum-likelihood programs and much higher than the performance of distance-based and parsimony approaches. The reduction of computing time is dramatic in comparison with other maximum-likelihood packages, while the likelihood maximization ability tends to be higher. For example, only 12 min were required on a standard personal computer to analyze a data set consisting of 500 rbcL sequences with 1,428 base pairs from plant plastids, thus reaching a speed of the same order as some popular distance-based and parsimony algorithms. This new method is implemented in the PHYML program, which is freely available on our web page: http://www.lirmm.fr/w3ifa/MAAS/. (Algorithm; computer simulations; maximum likelihood; phylogeny; rbcL; RDPII project.) The size of homologous sequence data sets has in- creased dramatically in recent years, and many of these data sets now involve several hundreds of taxa. More- over, current probabilistic sequence evolution models (Swofford et al., 1996 ; Page and Holmes, 1998 ), notably those including rate variation among sites (Uzzell and Corbin, 1971 ; Jin and Nei, 1990 ; Yang, 1996 ), require an increasing number of calculations. Therefore, the speed of phylogeny reconstruction methods is becoming a sig- nificant requirement and good compromises between speed and accuracy must be found. The maximum likelihood (ML) approach is especially accurate for building molecular phylogenies. Felsenstein (1981) brought this framework to nucleotide-based phy- logenetic inference, and it was later also applied to amino acid sequences (Kishino et al., 1990). Several vari- ants were proposed, most notably the Bayesian meth- ods (Rannala and Yang 1996; and see below), and the discrete Fourier analysis of Hendy et al. (1994), for ex- ample. Numerous computer studies (Huelsenbeck and Hillis, 1993; Kuhner and Felsenstein, 1994; Huelsenbeck, 1995; Rosenberg and Kumar, 2001; Ranwez and Gascuel, 2002) have shown that ML programs can recover the cor- rect tree from simulated data sets more frequently than other methods can. Another important advantage of the ML approach is the ability to compare different trees and evolutionary models within a statistical framework (see Whelan et al., 2001, for a review). However, like all optimality criterion-based phylogenetic reconstruction approaches, ML is hampered by computational difficul- ties, making it impossible to obtain the optimal tree with certainty from even moderate data sets (Swofford et al., 1996). Therefore, all practical methods rely on heuristics that obtain near-optimal trees in reasonable computing time. Moreover, the computation problem is especially difficult with ML, because the tree likelihood not only depends on the tree topology but also on numerical pa- rameters, including branch lengths. Even computing the optimal values of these parameters on a single tree is not an easy task, particularly because of possible local optima (Chor et al., 2000). The usual heuristic method, implemented in the pop- ular PHYLIP (Felsenstein, 1993 ) and PAUP ∗ (Swofford, 1999 ) packages, is based on hill climbing. It combines stepwise insertion of taxa in a growing tree and topolog- ical rearrangement. For each possible insertion position and rearrangement, the branch lengths of the resulting tree are optimized and the tree likelihood is computed. When the rearrangement improves the current tree or when the position insertion is the best among all pos- sible positions, the corresponding tree becomes the new current tree. Simple rearrangements are used during tree growing, namely "nearest neighbor interchanges" (see below), while more intense rearrangements can be used once all taxa have been inserted. The procedure stops when no rearrangement improves the current best tree. Despite significant decreases in computing times, no- tably in fastDNAml (Olsen et al., 1994 ), this heuristic becomes impracticable with several hundreds of taxa. This is mainly due to the two-level strategy, which sepa- rates branch lengths and tree topology optimization. In- deed, most calculations are done to optimize the branch lengths and evaluate the likelihood of trees that are finally rejected. New methods have thus been proposed. Strimmer and von Haeseler (1996) and others have assembled four- taxon (quartet) trees inferred by ML, in order to recon- struct a complete tree. However, the results of this ap- proach have not been very satisfactory to date (Ranwez and Gascuel, 2001 ). Ota and Li (2000, 2001) described

A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood.

Summary: We have developed a new software package, Molecular Evolutionary Genetics Analysis version 2 (MEGA2), for exploring and analyzing aligned DNA or protein sequences from an evolutionary perspective. MEGA2 vastly extends the capabilities of MEGA version 1 by: (1) facilitating analyses of large datasets; (2) enabling creation and analyses of groups of sequences; (3) enabling specification of domains and genes; (4) expanding the repertoire of statistical methods for molecular evolutionary studies; and (5) adding new modules for visual representation of input data and output results on the Microsoft Windows platform. Availability: http://www.megasoftware.net.

/pdf/mega2-molecular-evolutionary-genetics-analysis-software-4eaontmt16.pdf

MEGA2 : Molecular evolutionary genetics analysis software

http://theory.bio.uu.nl/immbio/Marks91.pdf

By-passing immunization: Human antibodies from V-gene libraries displayed on phage

Our knowledge of the structure and composition of genomes is rapidly progressing in pace with their sequencing. The emerging data show that a significant portion of eukaryotic genomes is composed of transposable elements (TEs). Given the abundance and diversity of TEs and the speed at which large quantities of sequence data are emerging, identification and annotation of TEs presents a significant challenge. Here we propose the first unified hierarchical classification system, designed on the basis of the transposition mechanism, sequence similarities and structural relationships, that can be easily applied by non-experts. The system and nomenclature is kept up to date at the WikiPoson web site.

A unified classification system for eukaryotic transposable elements

Methods are disclosed for the production of anti-self antibodies and antibody fragments, being antibodies or fragments of a particular species of mammal which bind self-antigens of that species. Methods comprise providing a library of replicable genetic display packages (rgdps), such as filamentous phage, each rgdp displaying at its surface a member of a specific binding pair which is an antibody or antibody fragment, and each rgdp containing nucleic acid sequence derived from a species of mammal. The nucleic acid sequence in each rgdp encodes a polypeptide chain which is a component part of the sbp member displayed at the surface of that rgdp. Anti-self antibody fragments are selected by binding with a self antigen from the said species of mammal. The displayed antibody fragments may be scFv, Fd, Fab or any other fragment which has the capability of binding antigen. Nucleic acid libraries used may be derived from a rearranged V-gene sequences of unimmunised mammal. Synthetic or artificial libraries are described and shown to be useful.

Production of anti-self antibodies from antibody segment repertoires and displayed on phage

Endogenous retroviruses (ERVs) result from permanent germline insertion of exogenous retroviruses within host genomes, and are abundant within mammalian genomes. The overwhelming majority of ERVs possess a relatively simple genomic organisation, lacking many of the accessory genes found in the more complex retroviruses. Furthermore, insertions prior to the radiation of mammalian orders lack closely related present day circulating exogenous counterparts. Foamy viruses (also termed Spumaviruses) are a superfamily of complex retroviruses that possess distinctive replication features, and are of great interest as both biological markers of zoonotic exposure risk and as candidate vectors for stem cell gene therapy. Despite a long evolutionary association with mammals, endogenous counterparts of infectious foamy viruses have been notably absent from mammalian genomes. We have discovered the first endogenous foamy virus (SloEFV) in the genomes of sloths (superorder: Xenarthra). SloEFV represents the first complex retrovirus to be described from the basal Xenarthran mammalian group. By determining the taxonomic distribution of related viruses in other Xenarthrans, and using bioinformatic approaches, we establish that SloEFV invaded sloth genomes prior to the colonization of continental South America by Boreoeutherian mammals. This observation, combined with exact congruence of branching order and statistically significant association of divergence between foamy virus and mammalian phylogenies, supports an extended cospeciation scenario under which foamy viruses remarkably similar to contemporary strains circulated in ancestral mammals >100 million years ago and diverged in concert with their hosts throughout the Cenozoic Era. Our discovery provides the first direct evidence for ancient and mammalian-wide origins of complex retroviruses, highlighting the role of evolutionary constraint in maintaining viral genome structure. We propose that the evolution of retroviral accessory genes and mammalian mechanisms of innate immunity are the products of a macroevolutionary conflict played out over a geological timescale. Furthermore, the extended coevolutionary relationship revealed by our analysis has implications for models of viral cross-species transmission and emergence.

/pdf/paleovirology-reveals-the-macroevolution-of-complex-3a06ri1hhj.pdf

Paleovirology reveals the macroevolution of complex retroviruses

Distinctive differences in long terminal repeat sequences between γ1 endogenous retroviruses of African and Eurasian suid species

: A new viral order unifying five families of reverse-transcribing viruses.

retroviruses, retroelements and their hosts Meet ing abstracts - A single PDF containing all abstracts in this Supplement is available here . http://www. biomedcentral.co m/content/pdf/17 42-4690-6-S2-inf o.pdf

/pdf/do-humans-have-replication-competent-endogenous-retroviruses-32g6545qi1.pdf

Michael Tristem

Papers

Paleovirology reveals the macroevolution of complex retroviruses

Distinctive differences in long terminal repeat sequences between γ1 endogenous retroviruses of African and Eurasian suid species

: A new viral order unifying five families of reverse-transcribing viruses.

Do humans have replication-competent endogenous retroviruses?

RetrovirusesDenisovan and Neanderthal