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Diminishing Returns on Intragenic Repeat Number Expansion in the Production of Signaling Peptides

Rogers, DW; McConnell, E; Miller, EL; Greig, D; (2017) Diminishing Returns on Intragenic Repeat Number Expansion in the Production of Signaling Peptides. Molecular Biology and Evolution , 34 (12) pp. 3176-3185. 10.1093/molbev/msx243. Green open access

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Abstract

Signalling peptides enable communication between cells, both within and between individuals, and are therefore key to the control of complex physiological and behavioural responses. Since their small sizes prevent direct transmission to secretory pathways, these peptides are often produced as part of a larger polyprotein comprising precursors for multiple related or identical peptides; the physiological and behavioural consequences of this unusual gene structure are not understood. Here, we show that the number of mature-pheromone-encoding repeats in the yeast α-mating-factor gene MFα1 varies considerably between closely related isolates of both S. cerevisiae and its sister species S. paradoxus. Variation in repeat number has important phenotypic consequences: increasing repeat number caused higher pheromone production and greater competitive mating success. However, the magnitude of the improvement decreased with increasing repeat number such that repeat amplification beyond that observed in natural isolates failed to generate more pheromone, and could actually reduce sexual fitness. We investigate multiple explanations for this pattern of diminishing returns and find that our results are most consistent with a translational trade-off: increasing the number of encoded repeats results in more mature pheromone per translation event, but also generates longer transcripts thereby reducing the rate of translation - a phenomenon known as length-dependent translation. Length-dependent translation may be a powerful constraint on the evolution of genes encoding repetitive or modular proteins, with important physiological and behavioural consequences across eukaryotes.

Type: Article
Title: Diminishing Returns on Intragenic Repeat Number Expansion in the Production of Signaling Peptides
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/molbev/msx243
Publisher version: http://doi.org/10.1093/molbev/msx243
Language: English
Additional information: © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Copy number variation, concerted evolution, length-dependent translation, genotype-to-phenotype, codon usage, protein tandem repeats
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery-pp.ucl.ac.uk/id/eprint/1573693
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