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

Abstract

Dosage-balance selection preserves functionally redundant duplicates (paralogs) at the optimum for their combined expression. Here we present a model of the dynamics of duplicate genes coevolving under dosage-balance selection. We call this the compensatory drift model. Results show that even when strong dosage-balance selection constrains total expression to the optimum, expression of each duplicate can diverge by drift from its original level. The rate of divergence slows as the strength of stabilizing selection, the size of the mutation effect, and/or the size of the population increases. We show that dosage-balance selection impedes neofunctionalization early after duplication but can later facilitate it. We fit this model to data from sodium channel duplicates in 10 families of teleost fish; these include two convergent lineages of electric fish in which one of the duplicates neofunctionalized. Using the model, we estimated the strength of dosage-balance selection for these genes. The results indicate that functionally redundant paralogs still may undergo radical functional changes after a prolonged period of compensatory drift.KEYWORDS duplication; expression evolution; dosage balance; neofunctionalization; whole-genome duplication T HE 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(Walsh , 2003Force 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 dosagesensitive 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(Birchler et al. , 2005Veitia 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 cons...

Parental legacy, demography, and introgression influenced the evolution of the two subgenomes of the tetraploidCapsella bursa-pastoris(Brassicaceae)

“…Our results also demonstrated that genes showing significant HSE largely overlapped between populations and these genes were not strongly enriched for GO terms. These genes probably evolve under a compensatory drift model (58). This was evident in the direction of the HSE, which was the same in all accessions.…”

Selective constraints on coding sequences of nervous system genes are a major determinant of duplicate gene retention in vertebrates

“…It is also possible that regulatory mutations first silence one duplicate copy, opening the way to its neutral degeneration (Thompson et al 2016). The neutral evolution of asymmetric expression levels between duplicate copies has indeed been reported (Gout and Lynch 2015;Lan and Pritchard 2016;Thompson et al 2016). But (i) this process was shown to require substantial amounts of time, and (ii) the evolution of expression levels in the nervous system is tightly controlled and slower than in other tissues (Pennacchio et al 2006;Brawand et al 2011;Barbosa-Morais et al 2012;Merkin et al 2012).…”

The role of structural pleiotropy and regulatory evolution in the retention of heteromers of paralogs

“…A possible explanation for this trend is that while the duplication of a single subunit of a complex may be deleterious by perturbing stoichiometry, duplication of all subunits at once may not cause such disadvantage since balance is preserved (Birchler and Veitia, 2012;Rice and McLysaght, 2017). Another possibility is that WGDs are maintained due to their dosage effects, which results in selection for the maintenance of their protein function (Gout and Lynch, 2015;Thompson et al, 2016) and at the same time favors the maintenance of HET complexes.…”