The relative roles of regulatory and protein evolution in the origin and loss of convergent phenotypic traits is a core question in evolutionary biology. Here we combine phylogenomic, epigenomic and developmental data to show that convergent evolution of regulatory regions, but not protein-coding genes, is associated with flightlessness in palaeognathous birds, a classic example of a convergent phenotype. Eleven new genomes, including a draft genome from an extinct moa, resolve palaeognath phylogeny and show that the incidence of independent, convergent accelerations among 284,000 conserved non-exonic elements is significantly more frequent in ratites than other bird lineages. Ratite-specific acceleration of conserved regions and measures of open chromatin across eight tissues in the developing chick identify candidate regulatory regions that may have modified or lost function in ratites. Enhancer activity assays conducted in the early developing chicken forelimb confirm that volant versions of a conserved element in the first intron of the TEAD1 gene display conserved enhancer activity, whereas an accelerated flightless version fails to drive reporter gene expression. Our results show that convergent molecular changes associated with loss of flight are largely regulatory in nature.

Computational biology has provided widely used and powerful software tools for testing and making inferences about biological data. In the face of increasing volumes of data, heuristic methods that trade software speed for mathematical completeness must be employed. We are interested in whether trade-offs between speed and accuracy are reasonable. Also, what factors are indicative of accurate software? In this work we mine published benchmarks of computational biology software, we collect data on the relative accuracy and speed of different software and then test to see what factors influence accuracy e.g. speed, author reputation, journal impact or recency. We found that author reputation, journal impact, the number of citations, software speed and age are not reliable predictors of software accuracy. This implies that useful bioinformatics software is not only the domain of famous senior researchers. In addition, we found that there exists an excess of slow and inaccurate software tools across multiple sub-disciplines of bioinformatics. Meanwhile, there are very few tools of middling accuracy and speed. We hypothesise that a strong publication bias unduly influences the publication and development of bioinformatic software tools. In other words, at present software that is not highly ranked on speed and not highly ranked on accuracy is difficult to publish due to editorial and reviewer practices. This leaves an unfortunate gap in the literature upon which future software refinements cannot be constructed.

Planning experiments using accurate prediction algorithms could mitigate failures in recombinant protein production. We have developed TISIGNER.com with the aim of addressing the technical challenges in recombinant protein production. We offer two web services, TIsigner (Translation Initiation coding region designer) and SoDoPE (Soluble Domain for Protein Expression), which are specialised in prediction/optimisation of recombinant protein expression and solubility, respectively. Importantly, TIsigner and SoDoPE are linked, which allows users to switch between the tools when optimising their genes of interest.