Abstract
The evolutionary mechanisms leading to duplicate gene retention are well understood, but the long-term impacts of paralog differentiation on the regulation of metabolism remain underappreciated. Here we experimentally dissect the functions of two pairs of ancient paralogs of the GALactose sugar utilization network in two yeast species. We show that the Saccharomyces uvarum network is more active, even as over-induction is prevented by a second co-repressor that the model yeast Saccharomyces cerevisiae lacks. Surprisingly, removal of this repression system leads to a strong growth arrest, likely due to overly rapid galactose catabolism and metabolic overload. Alternative sugars, such as fructose, circumvent metabolic control systems and exacerbate this phenotype. We further show that S. cerevisiae experiences homologous metabolic constraints that are subtler due to how the paralogs have diversified. These results show how the functional differentiation of paralogs continues to shape regulatory network architectures and metabolic strategies long after initial preservation.
Highlights
Gene duplication provides raw material for evolution to act upon
The first additional duplicate gene is GAL80B, which is a paralog of GAL80; this pair of paralogs was created by the whole genome duplication (WGD) event roughly 100 million years ago (Wolfe and Shields, 1997; Marcet-Houben and Gabaldon, 2015)
GAL80B has been retained in the S. uvarum-Saccharomyces eubayanus clade, but it was lost in the S. cerevisiae-Saccharomyces arboricola clade (Hittinger et al, 2010, 2004; Scannell et al, 2011; Caudy et al, 2013; Hittinger, 2013; Liti et al, 2013; Baker et al, 2015)
Summary
Gene duplication provides raw material for evolution to act upon. Even so, most duplicate genes are inactivated and become pseudogenes before fixation. The molecular mechanisms behind paralog retention and differentiation have attracted considerable attention, and several general models have been proposed, including neofunctionalization (Ohno, 1970; Zhang et al, 2002), gene dosage selection (Conant and Wolfe, 2007; Sandegren and Andersson, 2009; Conant et al, 2014), subfunctionalization by duplication-degeneration-complementation (Force et al, 1999), and subfunctionalization by escape from adaptive conflict (Hittinger and Carroll, 2007; Des Marais and Rausher, 2008). Theoretical studies have proposed that the fates of duplicate genes are rapidly determined after gene duplication events (Moore and Purugganan, 2003; Innan and Kondrashov, 2010). These models generally treat the preservation of duplicate genes as a race to distinguish
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call