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      Constructive Neutral Evolution 20 Years Later

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          Abstract

          Evolution has led to a great diversity that ranges from elegant simplicity to ornate complexity. Many complex features are often assumed to be more functional or adaptive than their simpler alternatives. However, in 1999, Arlin Stolzfus published a paper in the Journal of Molecular Evolution that outlined a framework in which complexity can arise through a series of non-adaptive steps. He called this framework Constructive Neutral Evolution (CNE). Despite its two-decade-old roots, many evolutionary biologists still appear to be unaware of this explanatory framework for the origins of complexity. In this perspective piece, we explain the theory of CNE and how it changes the order of events in narratives that describe the evolution of complexity. We also provide an extensive list of cellular features that may have become more complex through CNE. We end by discussing strategies to determine whether complexity arose through neutral or adaptive processes.

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          Most cited references77

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          Dosage sensitivity and the evolution of gene families in yeast.

          According to what we term the balance hypothesis, an imbalance in the concentration of the subcomponents of a protein-protein complex can be deleterious. If so, there are two consequences: first, both underexpression and overexpression of protein complex subunits should lower fitness, and second, the accuracy of transcriptional co-regulation of subunits should reflect the deleterious consequences of imbalance. Here we show that all these predictions are upheld in yeast (Saccharomyces cerevisiae). This supports the hypothesis that dominance is a by-product of physiology and metabolism rather than the result of selection to mask the deleterious effects of mutations. Beyond this, single-gene duplication of protein subunits is expected to be harmful, as this, too, leads to imbalance. As then expected, we find that members of large gene families are rarely involved in complexes. The balance hypothesis therefore provides a single theoretical framework for understanding components both of dominance and of gene family size.
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            The Origin and Diversification of Mitochondria.

            Mitochondria are best known for their role in the generation of ATP by aerobic respiration. Yet, research in the past half century has shown that they perform a much larger suite of functions and that these functions can vary substantially among diverse eukaryotic lineages. Despite this diversity, all mitochondria derive from a common ancestral organelle that originated from the integration of an endosymbiotic alphaproteobacterium into a host cell related to Asgard Archaea. The transition from endosymbiotic bacterium to permanent organelle entailed a massive number of evolutionary changes including the origins of hundreds of new genes and a protein import system, insertion of membrane transporters, integration of metabolism and reproduction, genome reduction, endosymbiotic gene transfer, lateral gene transfer and the retargeting of proteins. These changes occurred incrementally as the endosymbiont and the host became integrated. Although many insights into this transition have been gained, controversy persists regarding the nature of the original endosymbiont, its initial interactions with the host and the timing of its integration relative to the origin of other features of eukaryote cells. Since the establishment of the organelle, proteins have been gained, lost, transferred and retargeted as mitochondria have specialized into the spectrum of functional types seen across the eukaryotic tree of life.
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              Evolution of high mutation rates in experimental populations of E. coli.

              Most mutations are likely to be deleterious, and so the spontaneous mutation rate is generally held at a very low value. Nonetheless, evolutionary theory predicts that high mutation rates can evolve under certain circumstances. Empirical observations have previously been limited to short-term studies of the fates of mutator strains deliberately introduced into laboratory populations of Escherichia coli, and to the effects of intense selective events on mutator frequencies in E. coli. Here we report the rise of spontaneously originated mutators in populations of E. coli undergoing long-term adaptation to a new environment. Our results corroborate computer simulations of mutator evolution in adapting clonal populations, and may help to explain observations that associate high mutation rates with emerging pathogens and with certain cancers.
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                Author and article information

                Contributors
                smunozgo@asu.edu
                kerry.samerotte@asu.edu
                Journal
                J Mol Evol
                J Mol Evol
                Journal of Molecular Evolution
                Springer US (New York )
                0022-2844
                1432-1432
                19 February 2021
                19 February 2021
                2021
                : 89
                : 3
                : 172-182
                Affiliations
                GRID grid.215654.1, ISNI 0000 0001 2151 2636, School of Life Sciences, Biodesign Center for Mechanisms of Evolution, , Arizona State University, ; Tempe, AZ USA
                Author notes

                Handling editor: Aaron Goldman.

                Author information
                http://orcid.org/0000-0003-4666-2192
                Article
                9996
                10.1007/s00239-021-09996-y
                7982386
                33604782
                68ad24b6-ef1c-4c76-8509-81095b699136
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 18 October 2020
                : 13 January 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R35GM133674
                Award Recipient :
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                © Springer Science+Business Media, LLC, part of Springer Nature 2021

                Evolutionary Biology
                complexity,adaptation,neutrality,entrenchment,random genetic drift
                Evolutionary Biology
                complexity, adaptation, neutrality, entrenchment, random genetic drift

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