Geneious Basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data.

UNLABELLED: The two main functions of bioinformatics are the organization and analysis of biological data using computational resources. Geneious Basic has been designed to be an easy-to-use and flexible desktop software application framework for the organization and analysis of biological data, with a focus on molecular sequences and related data types. It integrates numerous industry-standard discovery analysis tools, with interactive visualizations to generate publication-ready images. One key contribution to researchers in the life sciences is the Geneious public application programming interface (API) that affords the ability to leverage the existing framework of the Geneious Basic software platform for virtually unlimited extension and customization. The result is an increase in the speed and quality of development of computation tools for the life sciences, due to the functionality and graphical user interface available to the developer through the public API. Geneious Basic represents an ideal platform for the bioinformatics community to leverage existing components and to integrate their own specific requirements for the discovery, analysis and visualization of biological data. AVAILABILITY AND IMPLEMENTATION: Binaries and public API freely available for download at http://www.geneious.com/basic, implemented in Java and supported on Linux, Apple OSX and MS Windows. The software is also available from the Bio-Linux package repository at http://nebc.nerc.ac.uk/news/geneiousonbl.

Adaptive divergence in experimental populations of Pseudomonas fluorescens. IV. Genetic constraints guide evolutionary trajectories in a parallel adaptive radiation.

The capacity for phenotypic evolution is dependent upon complex webs of functional interactions that connect genotype and phenotype. Wrinkly spreader (WS) genotypes arise repeatedly during the course of a model Pseudomonas adaptive radiation. Previous work showed that the evolution of WS variation was explained in part by spontaneous mutations in wspF, a component of the Wsp-signaling module, but also drew attention to the existence of unknown mutational causes. Here, we identify two new mutational pathways (Aws and Mws) that allow realization of the WS phenotype: in common with the Wsp module these pathways contain a di-guanylate cyclase-encoding gene subject to negative regulation. Together, mutations in the Wsp, Aws, and Mws regulatory modules account for the spectrum of WS phenotype-generating mutations found among a collection of 26 spontaneously arising WS genotypes obtained from independent adaptive radiations. Despite a large number of potential mutational pathways, the repeated discovery of mutations in a small number of loci (parallel evolution) prompted the construction of an ancestral genotype devoid of known (Wsp, Aws, and Mws) regulatory modules to see whether the types derived from this genotype could converge upon the WS phenotype via a novel route. Such types-with equivalent fitness effects-did emerge, although they took significantly longer to do so. Together our data provide an explanation for why WS evolution follows a limited number of mutational pathways and show how genetic architecture can bias the molecular variation presented to selection.

Evolution of relative synonymous codon usage in Human Immunodeficiency Virus type-1.

Mutation in Human Immunodeficiency Virus type-1 (HIV-1) is extremely rapid, a consequence of a low-fidelity viral reverse transcription process. The envelope gene has been shown to accumulate substitutions at a rate of approximately 1% per year and can frequently spend a long time in the host (approximately 10 years). The relative synonymous codon usage (RSCU) in HIV-1 is known to be different from that of the human host. However, by reengineering the protein coding sequences of HIV-1 to reflect the RSCU patterns observed in humans, a large increase in protein expression is observed. It is reasonable to suggest that within a host there may be a selective drive for change in the RSCU of HIV-1 towards human RSCU. To test this hypothesis we analyzed HIV-1 partial envelope sequences from eight patients sampled serially in time. For each sequence, an RSCU table was constructed. Sequences were labelled as "early" or "late" depending on whether they were sampled before or after the mid-point of the study. Using the RSCU values as descriptor variables, a Principal Components Analysis (PCA) was performed. The first three components clearly discriminated between early and late sequences. We also constructed pooled groupwise RSCU tables for early and late sequences. The viral RSCU values of each of the groups were correlated with human RSCU. If there is selection for host-adaptation in RSCU, we expect that "late" viral RSCUs would tend to be more highly correlated with human RSCU than "early" viral RSCUs. In fact, tests of significance suggest that this is the case. However, closer examination of the data revealed that the apparent trend towards human RSCU can be attributed to the homogenization of the codon usage by mutation pressure rather than host adaptation.