Long-term survival of duplicate genes despite absence of subfunctionalized expression.

Long-term survival of duplicate genes despite absence of subfunctionalized expression.

Xun Lan , Jonathan K Pritchard
doi: http://dx.doi.org/10.1101/019166

Gene duplication is a fundamental process in genome evolution. However, young duplicates are frequently degraded into pseudogenes by loss-of-function mutations. One standard model proposes that the main path for duplicate genes to avoid mutational destruction is by rapidly evolving subfunctionalized expression profiles. We examined this hypothesis using RNA-seq data from 46 human tissues. Surprisingly, we find that sub- or neofunctionalization of expression evolves very slowly, and is rare among duplications that arose within the placental mammals. Most mammalian duplicates are located in tandem and have highly correlated expression profiles, likely due to shared regulation, thus impeding subfunctionalization. Moreover, we also find that a large fraction of duplicate gene pairs exhibit a striking asymmetric pattern in which one gene has consistently higher expression. These asymmetrically expressed duplicates (AEDs) may persist for tens of millions of years, even though the lower-expressed copies tend to evolve under reduced selective constraint and are associated with fewer human diseases than their duplicate partners. We suggest that dosage-sharing of expression, rather than subfunctionalization, is more likely to be the initial factor enabling survival of duplicate gene pairs.

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