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      Parallel reorganization of protein function in the spindle checkpoint pathway through evolutionary paths in the fitness landscape that appear neutral in laboratory experiments

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Regulatory networks often increase in complexity during evolution through gene duplication and divergence of component proteins. Two models that explain this increase in complexity are: 1) adaptive changes after gene duplication, such as resolution of adaptive conflicts, and 2) non-adaptive processes such as duplication, degeneration and complementation. Both of these models predict complementary changes in the retained duplicates, but they can be distinguished by direct fitness measurements in organisms with short generation times. Previously, it has been observed that repeated duplication of an essential protein in the spindle checkpoint pathway has occurred multiple times over the eukaryotic tree of life, leading to convergent protein domain organization in its duplicates. Here, we replace the paralog pair in S. cerevisiae with a single-copy protein from a species that did not undergo gene duplication. Surprisingly, using quantitative fitness measurements in laboratory conditions stressful for the spindle-checkpoint pathway, we find no evidence that reorganization of protein function after gene duplication is beneficial. We then reconstruct several evolutionary intermediates from the inferred ancestral network to the extant one, and find that, at the resolution of our assay, there exist stepwise mutational paths from the single protein to the divergent pair of extant proteins with no apparent fitness defects. Parallel evolution has been taken as strong evidence for natural selection, but our results suggest that even in these cases, reorganization of protein function after gene duplication may be explained by neutral processes.

          Author summary

          Parallel evolution of protein domain organization following gene duplication has been demonstrated in the spindle checkpoint pathway leading to the hypothesis that this organization is likely to be adaptive. We test this hypothesis by reconstructing budding yeast strains with a spindle checkpoint pathway containing a protein with ancestral domain organization, and systematically perform stepwise duplication, degeneration and complementation of the duplicated protein. We show that, under laboratory conditions where the spindle checkpoint pathway is necessary for growth, degeneration of the ancestral pathway organization to the extant sub-functionalized proteins is consistent with a neutral model of duplication-degeneration-complementation.

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          Most cited references 48

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          The origins of genome complexity.

          Complete genomic sequences from diverse phylogenetic lineages reveal notable increases in genome complexity from prokaryotes to multicellular eukaryotes. The changes include gradual increases in gene number, resulting from the retention of duplicate genes, and more abrupt increases in the abundance of spliceosomal introns and mobile genetic elements. We argue that many of these modifications emerged passively in response to the long-term population-size reductions that accompanied increases in organism size. According to this model, much of the restructuring of eukaryotic genomes was initiated by nonadaptive processes, and this in turn provided novel substrates for the secondary evolution of phenotypic complexity by natural selection. The enormous long-term effective population sizes of prokaryotes may impose a substantial barrier to the evolution of complex genomes and morphologies.
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            Flexible nets. The roles of intrinsic disorder in protein interaction networks.

            Proteins participate in complex sets of interactions that represent the mechanistic foundation for much of the physiology and function of the cell. These protein-protein interactions are organized into exquisitely complex networks. The architecture of protein-protein interaction networks was recently proposed to be scale-free, with most of the proteins having only one or two connections but with relatively fewer 'hubs' possessing tens, hundreds or more links. The high level of hub connectivity must somehow be reflected in protein structure. What structural quality of hub proteins enables them to interact with large numbers of diverse targets? One possibility would be to employ binding regions that have the ability to bind multiple, structurally diverse partners. This trait can be imparted by the incorporation of intrinsic disorder in one or both partners. To illustrate the value of such contributions, this review examines the roles of intrinsic disorder in protein network architecture. We show that there are three general ways that intrinsic disorder can contribute: First, intrinsic disorder can serve as the structural basis for hub protein promiscuity; secondly, intrinsically disordered proteins can bind to structured hub proteins; and thirdly, intrinsic disorder can provide flexible linkers between functional domains with the linkers enabling mechanisms that facilitate binding diversity. An important research direction will be to determine what fraction of protein-protein interaction in regulatory networks relies on intrinsic disorder.
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              The frailty of adaptive hypotheses for the origins of organismal complexity.

               M. Lynch (2007)
              The vast majority of biologists engaged in evolutionary studies interpret virtually every aspect of biodiversity in adaptive terms. This narrow view of evolution has become untenable in light of recent observations from genomic sequencing and population-genetic theory. Numerous aspects of genomic architecture, gene structure, and developmental pathways are difficult to explain without invoking the nonadaptive forces of genetic drift and mutation. In addition, emergent biological features such as complexity, modularity, and evolvability, all of which are current targets of considerable speculation, may be nothing more than indirect by-products of processes operating at lower levels of organization. These issues are examined in the context of the view that the origins of many aspects of biological diversity, from gene-structural embellishments to novelties at the phenotypic level, have roots in nonadaptive processes, with the population-genetic environment imposing strong directionality on the paths that are open to evolutionary exploitation.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Genet
                PLoS Genet
                plos
                plosgen
                PLoS Genetics
                Public Library of Science (San Francisco, CA USA )
                1553-7390
                1553-7404
                14 April 2017
                April 2017
                : 13
                : 4
                Affiliations
                [1 ]Department of Cell & Systems Biology, University of Toronto, Toronto, Ontario, Canada
                [2 ]Center for Analysis of Evolution and Function, University of Toronto, Toronto, Ontario, Canada
                [3 ]Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, Ontario, Canada
                Washington University School of Medicine, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                • Conceptualization: ANNB AM.

                • Data curation: ANNB.

                • Formal analysis: ANNB.

                • Funding acquisition: ANNB AMM.

                • Investigation: ANNB BS SO EAL.

                • Methodology: ANNB.

                • Project administration: ANNB AMM BS TZ.

                • Resources: ANNB AMM.

                • Supervision: ANNB AMM TZ BS.

                • Validation: ANNB BS.

                • Visualization: ANNB BS AMM.

                • Writing – original draft: ANNB.

                • Writing – review & editing: ANNB AMM TZ EAL.

                [¤]

                Current address: Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, United States of America

                Article
                PGENETICS-D-16-02481
                10.1371/journal.pgen.1006735
                5409178
                28410373
                © 2017 Nguyen Ba et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 6, Tables: 0, Pages: 20
                Product
                Funding
                Funded by: NSERC
                Award Recipient :
                Funded by: NSERC
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100000024, Canadian Institutes of Health Research;
                Award ID: MOP-119579
                Award Recipient :
                ANNB is funded by a postgraduate scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC). AMM is supported by a NSERC Discovery grant and Canadian Institutes of Health research (grant MOP-119579).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Research and Analysis Methods
                Experimental Organism Systems
                Model Organisms
                Saccharomyces Cerevisiae
                Research and Analysis Methods
                Model Organisms
                Saccharomyces Cerevisiae
                Biology and Life Sciences
                Organisms
                Fungi
                Yeast
                Saccharomyces
                Saccharomyces Cerevisiae
                Research and Analysis Methods
                Experimental Organism Systems
                Yeast and Fungal Models
                Saccharomyces Cerevisiae
                Biology and Life Sciences
                Evolutionary Biology
                Evolutionary Genetics
                Biology and Life Sciences
                Evolutionary Biology
                Molecular Evolution
                Biology and Life Sciences
                Evolutionary Biology
                Evolutionary Processes
                Natural Selection
                Biology and Life Sciences
                Evolutionary Biology
                Molecular Evolution
                Gene Duplication
                Biology and Life Sciences
                Mycology
                Fungal Evolution
                Biology and Life Sciences
                Biochemistry
                Proteins
                Luminescent Proteins
                Green Fluorescent Protein
                Research and Analysis Methods
                Database and Informatics Methods
                Bioinformatics
                Sequence Analysis
                Sequence Motif Analysis
                Custom metadata
                vor-update-to-uncorrected-proof
                2017-04-28
                All relevant data are within the paper and its Supporting Information files.

                Genetics

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