GENIE: estimating demographic history from molecular phylogenies

GENIE implements a statistical framework for inferring the demographic history of a population from phylogenies that have been reconstructed from sampled DNA sequences. The methods are based on population genetic models known collectively as coalescent theory. AVAILABILITY: GENIE is available from http://evolve.zoo.ox.ac.uk. All popular operating systems are supported.     

Designer invariants for large phylogenies.

The Cavender-Felsenstein edge-length invariants for binary characters on 4-trees provide the starting point for the development of "customized" invariants for evaluating and comparing phylogenetic hypotheses. The binary character invariants may be generalized to k-valued characters without losing the quadratic nature of the invariants as functions of the theoretical frequencies f(UVXY) of observable character configurations (U at organism 1, V at 2, etc.). The key to the approach is that certain sets of these configurations constitute events which are probabilistically independent from other such sets, under the symmetric Markov change models studied. By introducing more complex sets of configurations, we find the quadratic invariants for 5-trees in the binary model and for individual edges in 6-trees or, indeed, in any size tree. The same technique allows us to formulate invariants for entire trees, but these are cubic functions for 6-trees and are higher-degree polynomials for larger trees. With k-valued characters and, especially, with large trees, the types of configuration sets (events) used in the simpler examples are too rare (i.e., their predicted frequencies are too low) to be useful, and the construction of meaningful pairs of independent events becomes an important and nontrivial task in designing invariants suited to testing specific hypotheses. In a very natural way, this approach fits in with well-known statistical methodology for contingency tables. We explore use of events such as "only transitions occur for character i (i.e., position i in a nucleic acid sequence) in subtree a" in analyzing a set of data on ribosomal RNA in the context of the controversy over the origins of archaebacteria, eubacteria, and eukaryotes.     

iCatch:a new strategy for capturing large DNA fragments using homing endonucleases

Natural genetic materials contain many biosynthetic gene clusters encoding potentially valuable natural products,many of which can be used directly without codon optimization or other manipulations.With the development of synthetic biology,several DNA assembly standards have been proposed,conveniently facilitating the reuse of natural materials.Among these standards,the iBrick assembly standard was developed by our laboratory to manipulate large DNA fragments,employing two homing endonucleases.Considering the difficulty of cloning large iBrick parts using conventional endonuclease-mediated restriction and ligation methods,we herein present a new method,known as iCatch,which readily captures biosynthetic gene clusters.As the clusters cloned by iCatch have the prefix and suffix of the iBrick standard,they serve as new iBrick parts and are therefore conducive to further editing and assembly with the iBrick standard.iCatch employs the natural homologous recombination system to flank the region of interest with I-Scel and PI-Pspl recognition sites,after which the genome is digested with I-Scel or PI-Pspl and the fragments are then self-ligated to clone the target DNA fragments.We used this method to successfully capture the actinorhodin biosynthetic cluster from Streptomyces coelicolor and then heterologously expressed this cluster in a thermophilic Streptomyces strain.We propose that iCatch can be used for the cloning of DNA sequences that are dozens of kilobases in length,facilitating the heterologous expression of microbial natural products.Moreover,this cloning methodology can be a complementary tool for the iBrick standard,especially in applications requiring the manipulation of large DNA fragments.     

pIQPNNI: parallel reconstruction of large maximum likelihood phylogenies

SUMMARY: IQPNNI is a program to infer maximum-likelihood phylogenetic trees from DNA or protein data with a large number of sequences. We present an improved and MPI-parallel implementation showing very good scaling and speed-up behavior.     

A new method for estimating locomotion type in large ground birds

Estimating the locomotion type of fossil ground birds is necessary for a better understanding of their ecology. Until now, only one method has allowed us to estimate the locomotion of fossil ground birds, but its application is complicated in the majority of fossil cases because it requires data from the three bones from the same hindlimb of one individual. Here, we propose a new method using only the maximum length and minimum width of the tarsometatarsus to estimate the locomotion of these fossil birds. This method is easy to apply and better distinguishes the intermediate cases between graviportal (walking) and cursorial (running) birds. This study shows that the species of large ground birds of the families Gastornithidae and Brontornithidae were all graviportal, probably because of their large body mass. More unexpectedly, it also shows that some Phorusrhacidae (e.g. Paraphysornis), usually described as cursorial birds, were in fact graviportal, probably because of their considerable body mass. All these new data about locomotion provide a better understanding of the ecology of fossil ground birds.     

Using phylogenies in conservation: new perspectives

The 2011 meeting of the European Ecological Federation took place in ávila, Spain, from 26th September to 29th September. The French Ecological Society (SFE) and the Foundation for Research on Biodiversity (FRB) sponsored a session entitled 'Evolutionary history, ecosystem function and conservation biology: new perspectives'. We report on the main insights obtained from this symposium.     

A landscape of coexistence for a large predator in a human dominated landscape

Human related mortality is a major threat for large carnivores all over the world and there is increasing evidence that large predators respond to human related risks in a similar way as prey respond to predation risk. This insight recently led to the conceptual development of a landscape of coexistence that can be used to identify areas which can sustain large predator populations in human dominated landscapes. In this study we applied the landscape of coexistence concept to a large predator in Europe. We investigated to what extent Eurasian lynx Lynx lynx habitat selection is affected by human disturbance in a human dominated landscape. More specifically, we were interested in the existence of a tradeoff between the availability of roe deer, one of their main prey and avoidance of human disturbance and how this affects the spatio‐temporal space use patterns of lynx. We found that lynx face a tradeoff between high prey availability and avoidance of human disturbance and that they respond to this by using areas of high prey availability (but also high human disturbance) during the night when human activity is low. Furthermore our analysis showed that lynx increase their travelling speed and remain more in cover when they are close to areas of high human disturbance. Despite clear behavioral adjustments in response to human presence, prey availability still proved to be the most important predictor of lynx occurrence at small spatial scale, whereas human disturbance was considerably less important. The results of our study demonstrate how spatio‐temporal adaptations in habitat selection enable large carnivores to persist in human dominated landscapes and demonstrate the usefulness of the concept of a landscape of coexistence to develop adaptive management plans for endangered populations of large carnivores.     

PATH: a task for the inference of phylogenies

Phylogenetic Analysis Task in Husar (PATH) is a task for the inference of phylogenies. It executes three phylogenetic methods and automatically chooses the evolutionary model for each set of data. The output of the tasks shows the consensus trees together with full results obtained from all executed methods. AVAILABILITY: PATH is available at the German EMBnet node after registration via www at http://genome.dkfz-heidelberg.de     

Shortest triplet clustering: reconstructing large phylogenies using representative sets

Background  

Understanding the evolutionary relationships among species based on their genetic information is one of the primary objectives in phylogenetic analysis. Reconstructing phylogenies for large data sets is still a challenging task in Bioinformatics.     

A new strategy for estimating two-locus recombination fractions under some natural inequality restrictions

Linkage analysis is now being widely used to map markers on each chromosome in the human genome, to map genetic diseases, and to identify genetic forms of common diseases. Two-locus linkage analysis and multi-locus analysis have been investigated comprehensively, and many computer programs have been developed to perform linkage analysis. Yet there exists a shortcoming in traditional methods, i.e., the parameter space of two-locus recombination fractions has not been emphasized sufficiently in the usual analyses. In this paper, we propose a new strategy for estimating the two-locus recombination fractions based on data of backcross family in the framework of some natural and necessary parameter restrictions. The new strategy is based on a restricted projection algorithm, which can provide fast reasonable estimates of recombination fraction, and can therefore serve as a superior alternative algorithm. Results obtained from both real and simulated data indicate that the new algorithm performs well in the estimation of recombination fractions and outperforms current methods.     

A new strategy for backbone resonance assignment in large proteins using a MQ-HACACO experiment

A new strategy of backbone resonance assignment is proposed based on a combination of the most sensitive TROSY-type triple resonance experiments such as TROSY-HNCA and TROSY-HNCO with a new 3D multiple-quantum HACACO experiment. The favourable relaxation properties of the multiple-quantum coherences and signal detection using the ¹³C antiphase coherences optimize the performance of the proposed experiment for application to larger proteins. In addition to the ¹H^N, ¹⁵N,¹³C and ¹³C chemical shifts the 3D multiple-quantum HACACO experiment provides assignment for the ¹H resonances in constrast to previously proposed experiments for large proteins. The strategy is demonstrated with the 44 kDa uniformly ¹⁵N,¹³C-labeled and fractionally 35% deuterated trimeric B. subtilis Chorismate Mutase measured at 20°C and 9°C. Measurements at the lower temperature indicate that the new strategy can be applied to even larger proteins with molecular weights up to 80 kDa.     

BitPhylogeny: a probabilistic framework for reconstructing intra-tumor phylogenies

Cancer has long been understood as a somatic evolutionary process, but many details of tumor progression remain elusive. Here, we present BitPhylogeny, a probabilistic framework to reconstruct intra-tumor evolutionary pathways. Using a full Bayesian approach, we jointly estimate the number and composition of clones in the sample as well as the most likely tree connecting them. We validate our approach in the controlled setting of a simulation study and compare it against several competing methods. In two case studies, we demonstrate how BitPhylogeny reconstructs tumor phylogenies from methylation patterns in colon cancer and from single-cell exomes in myeloproliferative neoplasm.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-015-0592-6) contains supplementary material, which is available to authorized users.     

SHOT: a web server for the construction of genome phylogenies

With the increasing availability of genome sequences, new methods are being proposed that exploit information from complete genomes to classify species in a phylogeny. Here we present SHOT, a web server for the classification of genomes on the basis of shared gene content or the conservation of gene order that reflects the dominant, phylogenetic signal in these genomic properties. In general, the genome trees are consistent with classical gene-based phylogenies, although some interesting exceptions indicate massive horizontal gene transfer. SHOT is a useful tool for analysing the tree of life from a genomic point of view. It is available at http://www.Bork.EMBL-Heidelberg.de/SHOT.     

反基因策略：基因治疗的新方向

合成的富含嘌呤或嘧啶的脱氧寡核苷酸可与双链ＤＮＡ内特定的同聚嘌呤、同聚嘧啶序列结合形成稳定的三螺旋结构（三链ＤＮＡ）。已在体外及体内证实了在靶基因内形成的局部三链ＤＮＡ可抑制其转录,这给肿瘤和病毒感染性疾病的治疗提示了新的方向,人们称之为反基因策略。然而,三链ＤＮＡ的稳定性不够理想和靶序列的选择范围较窄等问题的存在,在一定程度上限制了反基因策略的应用。     

The family Agaricaceae: phylogenies and two new white-spored genera

A well resolved phylogeny of the Agaricaceae based on partial rpb2 sequences is presented from a wide geographic and systematic sampling of the family and compared to phylogenies based on nrLSU and tef1 sequences. A smaller dataset of the family focusing on the Agaricus clade of nrITS sequences and a combined dataset were used to determine the position of several white-spored taxa from northern Thailand. Two new genera are described from Thailand. Coniolepiota accommodates Lepiota spongodes, a gray-lilac-purple floccose white-spored species with a wide distribution in tropical Asia; Eriocybe has a white wooly felt-like covering of pileus and stipe, white spores and is described with one new species E. chionea, so far known only from northern Thailand. These new genera are closely related to three genera with colored spores (viz. Agaricus, Heinemannomyces and Clarkeinda) and not to other white-spored taxa.     

Informational gene phylogenies do not support a fourth domain of life for nucleocytoplasmic large DNA viruses

Mimivirus is a nucleocytoplasmic large DNA virus (NCLDV) with a genome size (1.2 Mb) and coding capacity ( 1000 genes) comparable to that of some cellular organisms. Unlike other viruses, Mimivirus and its NCLDV relatives encode homologs of broadly conserved informational genes found in Bacteria, Archaea, and Eukaryotes, raising the possibility that they could be placed on the tree of life. A recent phylogenetic analysis of these genes showed the NCLDVs emerging as a monophyletic group branching between Eukaryotes and Archaea. These trees were interpreted as evidence for an independent "fourth domain" of life that may have contributed DNA processing genes to the ancestral eukaryote. However, the analysis of ancient evolutionary events is challenging, and tree reconstruction is susceptible to bias resulting from non-phylogenetic signals in the data. These include compositional heterogeneity and homoplasy, which can lead to the spurious grouping of compositionally-similar or fast-evolving sequences. Here, we show that these informational gene alignments contain both significant compositional heterogeneity and homoplasy, which were not adequately modelled in the original analysis. When we use more realistic evolutionary models that better fit the data, the resulting trees are unable to reject a simple null hypothesis in which these informational genes, like many other NCLDV genes, were acquired by horizontal transfer from eukaryotic hosts. Our results suggest that a fourth domain is not required to explain the available sequence data.     

A new strategy for estimating recombination fractions between dominant markers from an F2 population

Although most high-density linkage maps have been constructed from codominant markers such as single-nucleotide polymorphisms (SNPs) and microsatellites due to their high linkage information, dominant markers can be expected to be even more significant as proteomic technique becomes widely applicable to generate protein polymorphism data from large samples. However, for dominant markers, two possible linkage phases between a pair of markers complicate the estimation of recombination fractions between markers and consequently the construction of linkage maps. The low linkage information of the repulsion phase and high linkage information of coupling phase have led geneticists to construct two separate but related linkage maps. To circumvent this problem, we proposed a new method for estimating the recombination fraction between markers, which greatly improves the accuracy of estimation through distinction between the coupling phase and the repulsion phase of the linked loci. The results obtained from both real and simulated F2 dominant marker data indicate that the recombination fractions estimated by the new method contain a large amount of linkage information for constructing a complete linkage map. In addition, the new method is also applicable to data with mixed types of markers (dominant and codominant) with unknown linkage phase.     

Changing the landscape of autism research: the autism genetic resource exchange

Autism Speaks' Autism Genetic Resource Exchange (AGRE) represents the largest private collection of genetic and phenotype data for families with ASD that is made available to qualified researchers worldwide. The availability of large and comprehensive registries that include detailed phenotype and genetic information for individuals affected with an ASD and family members is crucial for the discovery of autism susceptibility genes and the development and application of biologically based approaches to diagnosis and treatment. The model that AGRE has developed can be applied broadly to other disorders with complex etiologies.