Epigenetic Silencing May Aid Evolution by Gene Duplication

Abstract

Gene duplication is commonly regarded as the main evolutionary path toward the gain of a new function. However, even with gene duplication, there is a loss-versus-gain dilemma: most newly born duplicates degrade to pseudogenes, since degenerative mutations are much more frequent than advantageous ones. Thus, something additional seems to be needed to shift the loss versus gain equilibrium toward functional divergence. We suggest that epigenetic silencing of duplicates might play this role in evolution. This study began when we noticed in a previous publication (Lynch M, Conery JS [2000] Science 291:1151-1155) that the frequency of functional young gene duplicates is higher in organisms that have cytosine methylation (H. sapiens, M. musculus, and A. thaliana) than in organisms that do not have methylated genomes (S. cerevisiae, D. melanogaster, and C. elegans). We find that genome data analysis confirms the likelihood of much more efficient functional divergence of gene duplicates in mammals and plants than in yeast, nematode, and fly. We have also extended the classic model of gene duplication, in which newly duplicated genes have exactly the same expression pattern, to the case when they are epigenetically silenced in a tissue- and/or developmental stage-complementary manner. This exposes each of the duplicates to negative selection, thus protecting from "pseudogenization." Our analysis indicates that this kind of silencing (i) enhances evolution of duplicated genes to new functions, particularly in small populations, (ii) is quite consistent with the subfunctionalization model when degenerative but complementary mutations affect different subfunctions of the gene, and (iii) furthermore, may actually cooperate with the DDC (duplication-degeneration-complementation) process.

DNA methylation and evolution of duplicate genes

“…Thus, not all duplicate genes exhibit heavy DNA methylation. Nevertheless, our results are consistent with the "expression reduction model," which states that heavy DNA methylation following the initial duplication event can suppress the expression of duplicate genes, thus providing "buffering" while mutations begin to accumulate (12,15). Moreover, we show that promoter DNA methylation of duplicates decreases with evolutionary time (Fig.…”

“…We focus on DNA methylation. It has been proposed that epigenetic mechanisms such as DNA methylation may facilitate evolution by gene duplication (12). Rodin and Riggs (12) have demonstrated by computational modeling that rates of functional diversification such as subfunctionalization and neofunctionalization increase when epigenetic silencing of duplicates is possible.…”

“…Rodin and Riggs (12) have demonstrated by computational modeling that rates of functional diversification such as subfunctionalization and neofunctionalization increase when epigenetic silencing of duplicates is possible. This advantage of epigenetic silencing is particularly significant when effective population sizes are small, as in humans (12).…”

Simultaneous expansions of microRNAs and protein‐coding genes by gene/genome duplications in early vertebrates

“…Genome-wide duplications may have also initiated rapid and massive genomic alterations (Ohno, '70;Gu et al, 2005). Consequently, epigenetic status, such as methylation, imprinting or miRNA targeting, may differ between duplicated genes, a process that could occur much earlier than nucleotide mutations in the regulatory region (Rodin and Riggs, 2003;Rapp and Wendel, 2005;Rodin et al, 2005;Zheng, 2008). As a gene-wide duplication event is to simultaneously double the genetic elements related to the epigenetic machinery and protein-encoding genes, the co-evolution facilitated by these major genomic alterations in the early vertebrates has been an interesting issue but highly controversial.…”

Correlations between Quantitative Measures of Genome Evolution, Expression and Function

“…Several theoretical explanations have been proposed to resolve this apparent paradox, in particular, the subfunctionalization model, whereby young duplicate genes undergo partial loss of function, leading first to retention of both copies necessary for genetic complementation between them and, later, to functional divergence; 24 dosage effect, postulating direct selective advantage of the increase of gene (product) dosage brought about by duplication, 25 and tissue-or development stage-specific epigenetic silencing of one of the duplicates, which exposes both copies to purifying selection. 26 The observed reduction of species-wide sequence polymorphism in recently duplicated genes in Arabidopsis suggests a role of selection sweeps in initial fixation of duplications. 27 Interestingly, as a counter-point to the common notion of the creative role of gene duplication, a gene loss that "compressed" functions of two paralogs into a single copy has been suggested as the main event that "unlocked" the evolutionary path to flowering plants.…”