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Response to Comment on "Ancient origins of allosteric activation in a Ser-Thr kinase"

Science

Park et al. question one out of seven findings from Hadzipasic et al.: whether TPX2 allosterically regulates the oldest Aurora. We had already addressed the two concerns raised--sparse sequence sampling and not forcing the gene to the species tree--before publication. Moreover, we believe their ancestral sequence reconstruction would be consistent with a nonallosteric common ancestor, and we show large sequence differences caused by species tree–enforced gene trees. The key findings in Hadzipasic et al. (1) are that (i) autophosphorylation is the ancient allosteric regulation for Aurora kinases; (ii) a gradual increase in allosteric activation took place during the holozoan evolution; (iii) an allosteric network in Aurora exists that, when mutated, alters allosteric activity; (iv) allosteric activation by TPX2 is entirely encoded in the kinase; (v) the interface between Aurora and TPX2 is co-conserved; (vi) evolution of specificity in signaling happens on binding affinity; and (vii) the oldest ancestral Aurora is not allosterically activated by TPX2. Notably, even though the ASR calculations differ, we believe the outcome is consistent with, rather than contradicting, the finding. The two concerns raised are (i) the small number of modern sequences used in the ASR calculations and (ii) the mismatch between the gene tree and the species tree.

  Country: Asia > Indonesia > Bali (0.05)
  Genre: Research Report > New Finding (0.30)

Phylotastic: An Experiment in Creating, Manipulating, and Evolving Phylogenetic Biology Workflows Using Logic Programming

Nguyen, Thanh Hai, Pontelli, Enrico, Son, Tran Cao

arXiv.org Artificial Intelligence

Evolutionary Biologists have long struggled with the challenge of developing analysis workflows in a flexible manner, thus facilitating the reuse of phylogenetic knowledge. An evolutionary biology workflow can be viewed as a plan which composes web services that can retrieve, manipulate, and produce phylogenetic trees. The Phylotastic project was launched two years ago as a collaboration between evolutionary biologists and computer scientists, with the goal of developing an open architecture to facilitate the creation of such analysis workflows. While composition of web services is a problem that has been extensively explored in the literature, including within the logic programming domain, the incarnation of the problem in Phylotastic provides a number of additional challenges. Along with the need to integrate preferences and formal ontologies in the description of the desired workflow, evolutionary biologists tend to construct workflows in an incremental manner, by successively refining the workflow, by indicating desired changes (e.g., exclusion of certain services, modifications of the desired output). This leads to the need of successive iterations of incremental replanning, to develop a new workflow that integrates the requested changes while minimizing the changes to the original workflow. This paper illustrates how Phylotastic has addressed the challenges of creating and refining phylogenetic analysis workflows using logic programming technology and how such solutions have been used within the general framework of the Phylotastic project.


Data Requirement for Phylogenetic Inference from Multiple Loci: A New Distance Method

Dasarathy, Gautam, Nowak, Robert, Roch, Sebastien

arXiv.org Machine Learning

We consider the problem of estimating the evolutionary history of a set of species (phylogeny or species tree) from several genes. It is known that the evolutionary history of individual genes (gene trees) might be topologically distinct from each other and from the underlying species tree, possibly confounding phylogenetic analysis. A further complication in practice is that one has to estimate gene trees from molecular sequences of finite length. We provide the first full data-requirement analysis of a species tree reconstruction method that takes into account estimation errors at the gene level. Under that criterion, we also devise a novel reconstruction algorithm that provably improves over all previous methods in a regime of interest.