Academic journal article Genetics

Compensatory Drift and the Evolutionary Dynamics of Dosage-Sensitive Duplicate Genes

Academic journal article Genetics

Compensatory Drift and the Evolutionary Dynamics of Dosage-Sensitive Duplicate Genes

Article excerpt

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THE fate of duplicate genes is characterized by two extremes: degeneration and the origin of biological novelty. Early models for the evolutionary dynamics of duplicates suggested that typically one member of a duplicate pair would quickly degenerate into a nonfunctional pseudogene (Haldane 1933; Ohno 1970). More rarely, a duplicate instead may evolve a novel function in a process called neofunctionalization (Muller 1936; Ohno 1970; Ohta 1987). The time scale for either pseudogenization or neofunctionalization is expected to be on the order of a few million years (Lynch and Conery 2000).

Recent research indicates, however, that the evolutionary dynamics for many duplicates are not so simple (Walsh 1995, 2003; Force et al. 1999; Papp et al. 2003; He and Zhang 2005; Rastogi and Liberles 2005; Scannell and Wolfe 2008; Qian et al. 2010; Kondrashov 2012). Some genes are dosage sensitive, meaning that a change in their copy number alters expression and disrupts the stoichiometric balance of their gene products with those of other genes. Duplicates of dosageCopyright sensitive genes typically will fix in a population only if they originate in a whole-genome duplication (WGD), where all interacting partners duplicate together. Selection to maintain the stoichiometric relations between the products of duplicate genes, termed dosage-balance selection, can preserve duplicates as functionally redundant copies for prolonged periods of time (Birchler et al. 2001, 2005; Veitia 2002; Papp et al. 2003; Aury et al. 2006; Blomme et al. 2006; Freeling and Thomas 2006; Stranger et al. 2007; Qian and Zhang 2008; Edger and Pires 2009; Makino and McLysaght 2010; Konrad et al. 2011; Birchler and Veitia 2012; McGrath et al. 2014a).

Recent data on a pair of sodium channel duplicates in teleost fish are consistent with the expectations of the dosagebalance hypothesis (Thompson et al. 2014). The two duplicates, also called paralogs, have been conserved in muscle cells for over 300 million years since the teleost-specific WGD. In two independent lineages of electric fish, however, only one of the sodium channels is expressed in muscle cells. The other duplicate neofunctionalized and now plays a key role in the electric organ (Novak et al. 2006; Zakon et al. 2006; Arnegard et al. 2010). These convergent neofunctionalization events happened on a very slow time scale, more than 100 million years after duplication (Arnegard et al. 2010; Lavoué et al. 2012; Betancur-R et al. 2013). The phylogenetic context for the evolution of the duplicates is shown in Figure 1.

Thompson et al. (2014) proposed that in the teleost ancestor the duplicates were preserved after WGD by dosagebalance selection. They hypothesized that under this selective constraint, one paralog gradually drifted to lower expression levels, while the other compensated by evolving higher expression. Eventually, one paralog contributed so little to its original function that it could be neofunctionalized in the electric organ without major compromise to muscles. This mode of evolution also may explain comparative expression patterns observed in some ciliates (Gout and Lynch 2015) as well as some mammals (Lan and Pritchard 2015). This hypothesis raises theoretical and quantitative issues not previously explored. Can dosage-balance selection in fact maintain duplicates for hundreds of millions of years? Will this mode of evolution produce comparative patterns in a phylogeny that are distinct from other models? And how does this evolutionary process affect the likelihood of neofunctionalization?

Here we develop a model for the evolution of paralog expression under dosage-balance selection. It envisions a process, which we call compensatory drift, in which paralogs diverge by weakly selected mutations that fix largely by drift. The model shows how key genetic parameters determine the time scale over which duplicates are maintained before one is lost or neofunctionalizes. …

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