Following Gene Duplication, Paralog Interference Constrains Transcriptional Circuit Evolution

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Science  04 Oct 2013:
Vol. 342, Issue 6154, pp. 104-108
DOI: 10.1126/science.1240810

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Two Are Not Necessarily Better Than One

Gene duplication is one of the major drivers of the evolution of gene and protein networks. However, specific examples of how genes change to maintain two paralogous gene copies within an organism are relatively rare. Baker et al. (p. 104) examined the functional divergence of the paralogs Mcm1 and Arg80, MADS-box transcription factors in the yeast Saccharomyces cerevisiae. The partitioning of ancestral functions in a fungal transcription factor appeared to be affected by competitive interference between the newly formed gene duplicates. Thus, in yeast, gene duplication has created a selective conflict between the paralogs, which appear to have driven the evolution of a novel protein function.


Most models of gene duplication assume that the ancestral functions of the preduplication gene are independent and can therefore be neatly partitioned between descendant paralogs. However, many gene products, such as transcriptional regulators, are components within cooperative assemblies; here, we show that a natural consequence of duplication and divergence of such proteins can be competitive interference between the paralogs. Our example is based on the duplication of the essential MADS-box transcriptional regulator Mcm1, which is found in all fungi and regulates a large set of genes. We show that a set of historical amino acid sequence substitutions minimized paralog interference in contemporary species and, in doing so, increased the molecular complexity of this gene regulatory network. We propose that paralog interference is a common constraint on gene duplicate evolution, and its resolution, which can generate additional regulatory complexity, is needed to stabilize duplicated genes in the genome.

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