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

作者：Rogers David W^*; McConnell Ellen; Miller Eric L; Greig Duncan

来源：Molecular Biology and Evolution, 2017, 34(12): 3176-3185.

DOI：10.1093/molbev/msx243

• protein tandem repeats
• codon usage
• genotype-to-phenotype
• length-dependent translation
• concerted evolution
• copy number variation

Signaling peptides enable communication between cells, both within and between individuals, and are therefore key to the control of complex physiological and behavioral 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 behavioral consequences of this unusual gene structure are not understood. Here, we show that the number of mature-pheromone-encoding repeats in the yeast alpha-mating-factor gene MF alpha 1 varies considerably between closely related isolates of both Saccharomyces cerevisiae and its sister species Saccharomyces 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 behavioral consequences across eukaryotes.

• 出版日期2017-12