Abstract
The method of phylogenetic ancestral sequence reconstruction is a powerful approach for studying evolutionary relationships among protein sequence, structure, and function. In particular, this approach allows investigators to (1) reconstruct and “resurrect” (that is, synthesize in vivo or in vitro) extinct proteins to study how they differ from modern proteins, (2) identify key amino acid changes that, over evolutionary timescales, have altered the function of the protein, and (3) order historical events in the evolution of protein function. Widespread use of this approach has been slow among molecular biologists, in part because the methods require significant computational expertise. Here we present PhyloBot, a web-based software tool that makes ancestral sequence reconstruction easy. Designed for non-experts, it integrates all the necessary software into a single user interface. Additionally, PhyloBot provides interactive tools to explore evolutionary trajectories between ancestors, enabling the rapid generation of hypotheses that can be tested using genetic or biochemical approaches. Early versions of this software were used in previous studies to discover genetic mechanisms underlying the functions of diverse protein families, including V-ATPase ion pumps, DNA-binding transcription regulators, and serine/threonine protein kinases. PhyloBot runs in a web browser, and is available at the following URL: http://www.phylobot.com. The software is implemented in Python using the Django web framework, and runs on elastic cloud computing resources from Amazon Web Services. Users can create and submit jobs on our free server (at the URL listed above), or use our open-source code to launch their own PhyloBot server.
Highlights
Over the last decade, several innovative studies analyzed evolutionary trajectories of ancient genes in order to discover important relationships between present-day gene sequence, PLOS Computational Biology | DOI:10.1371/journal.pcbi.1004976 July 29, 2016PhyloBot Web Portal
These discoveries relied on the methods of ancestral sequence reconstruction, in which models of amino acid evolution are used to infer ancient protein sequences at multiple points in a gene family history [7]
PhyloBot is a web portal that automates the reconstruction of ancestral amino acid sequences
Summary
Several innovative studies analyzed evolutionary trajectories of ancient genes in order to discover important relationships between present-day gene sequence, PLOS Computational Biology | DOI:10.1371/journal.pcbi.1004976 July 29, 2016PhyloBot Web Portal. These discoveries relied on the methods of ancestral sequence reconstruction, in which models of amino acid evolution are used to infer ancient protein sequences at multiple points in a gene family history [7]. Ancestral reconstruction currently requires dozens of software tools, the computational skills to combine them, knowledge about phylogenetic models, and the programming abilities to deal with multiple file formats (many of them esoteric). PhyloBot, described here, is new software that automates ancestral sequence reconstruction.
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