Coregulation of tandem duplicate genes slows evolution of subfunctionalization in mammals

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Science  20 May 2016:
Vol. 352, Issue 6288, pp. 1009-1013
DOI: 10.1126/science.aad8411

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Evolutionary maintenance of gene duplications

Understanding genetic redundancy—the maintenance of multiple copies of a gene after duplication—and its relevance to genetic evolution have long been debated. Lan and Pritchard examined gene duplicates within human and other mammalian genomes. The expression of genes appears to be controlled by dosage balance and tight coregulation of tandem duplicates. They found little evidence for gene copies evincing significantly different expression patterns. However, such changes can evolve later, after gene copies become physically separated within the genome and thus are no longer jointly regulated.

Science, this issue p. 1009


Gene duplication is a fundamental process in genome evolution. However, most young duplicates are degraded by loss-of-function mutations, and the factors that allow some duplicate pairs to survive long-term remain controversial. One class of models to explain duplicate retention invokes sub- or neofunctionalization, whereas others focus on sharing of gene dosage. RNA-sequencing data from 46 human and 26 mouse tissues indicate that subfunctionalization of expression evolves slowly and is rare among duplicates that arose within the placental mammals, possibly because tandem duplicates are coregulated by shared genomic elements. Instead, consistent with the dosage-sharing hypothesis, most young duplicates are down-regulated to match expression levels of single-copy genes. Thus, dosage sharing of expression allows for the initial survival of mammalian duplicates, followed by slower functional adaptation enabling long-term preservation.

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