Multiple Mechanisms Promote the Retained Expression of Gene Duplicates in the Tetraploid Frog Xenopus laevis

Abstract

Gene duplication provides a window of opportunity for biological variants to persist under the protection of a co-expressed copy with similar or redundant function. Duplication catalyzes innovation (neofunctionalization), subfunction degeneration (subfunctionalization), and genetic buffering (redundancy), and the genetic survival of each paralog is triggered by mechanisms that add, compromise, or do not alter protein function. We tested the applicability of three types of mechanisms for promoting the retained expression of duplicated genes in 290 expressed paralogs of the tetraploid clawed frog, Xenopus laevis. Tests were based on explicit expectations concerning the ka/ks ratio, and the number and location of nonsynonymous substitutions after duplication. Functional constraints on the majority of paralogs are not significantly different from a singleton ortholog. However, we recover strong support that some of them have an asymmetric rate of nonsynonymous substitution: 6% match predictions of the neofunctionalization hypothesis in that (1) each paralog accumulated nonsynonymous substitutions at a significantly different rate and (2) the one that evolves faster has a higher ka/ks ratio than the other paralog and than a singleton ortholog. Fewer paralogs (3%) exhibit a complementary pattern of substitution at the protein level that is predicted by enhancement or degradation of different functional domains, and the remaining 13% have a higher average ka/ks ratio in both paralogs that is consistent with altered functional constraints, diversifying selection, or activity-reducing mutations after duplication. We estimate that these paralogs have been retained since they originated by genome duplication between 21 and 41 million years ago. Multiple mechanisms operate to promote the retained expression of duplicates in the same genome, in genes in the same functional class, over the same period of time following duplication, and sometimes in the same pair of paralogs. None of these paralogs are superfluous; degradation or enhancement of different protein subfunctions and neofunctionalization are plausible hypotheses for the retained expression of some of them. Evolution of most X. laevis paralogs, however, is consistent with retained expression via mechanisms that do not radically alter functional constraints, such as selection to preserve post-duplication stoichiometry or temporal, quantitative, or spatial subfunctionalization.

Evolutionarily conserved A-to-I editing increases protein stability of the alternative splicing factorNova1

“…19 This contrasts with comparisons among non-amniotes: for instance, two chondrichthyan species (Callorhincus milli and Scyliorhinus canicula, diverged~250-270 million years ago 20 ) show far more sequence changes (19% nucleotide divergence) in the orthologous region (Fig. S2B), and even the congenitor species X. tropicalis and X. laevis (diverged only 50-70 million years ago 21,22 ) have accumulated more differences (6%) than any pair of studied amniotes (Fig. S2C).…”

Subfunctionalization of Paralogous Aryl Hydrocarbon Receptors from the FrogXenopus Laevis: Distinct Target Genes and Differential Responses to Specific Agonists in a Single Cell Type

“…Many pairs of alloalleles are retained in X. laevis, a consequence of several potential mechanisms that are not mutually exclusive. These include spatiotemporal subfunctionalization, neofunctionalization, complementary degeneration of functional domains, and maintenance of post-duplication stoichiometry (Chain and Evans, 2006;Hellsten et al, 2007) Five hours after transfection, cells were treated with 100 nM FICZ or DMSO (0.6%) for 18 h. Transcriptional activity was measured in triplicate using a luciferase reporter gene driven by a portion of the mouse CYP1A1 enhancer.…”

“…Like many X. laevis "alloalleles", they arose in a genome duplication approximately 50 MYA (Evans et al, 2004). This duplication resulted from interspecies hybridization, producing an allotetraploid species from which X. laevis (and other polyploid members of the genus) evolved (Chain and Evans, 2006;Evans et al, 2004;Hellsten et al, 2007). The resulting genome contains 2 "subgenomes", each with 9 homeologous chromosomes.…”

“…Conventional wisdom holds that X. laevis alloalleles typically have redundant functions, since emergence of developmental phenotypes often requires morpholino knockdown of both genes (Abu-Daya et al, 2012). However, some gene duplicates show evidence of functional divergence (Chain and Evans, 2006;Hellsten et al, 2007). The objective of this study was to test the hypothesis that endogenous AHR1a and AHR1b have different molecular functions in XLK-WG (Martin et al, 1998), a frog cell line used previously for AHR characterization (Iwamoto et al, 2012;Laub et al, 2010).…”

Homoeologous chromosomes of Xenopus laevis are highly conserved after whole-genome duplication

“…In Silurana, X. tropicalis and another diploid species underwent allopolyploidization to give rise to three tetraploid species with 40 chromosomes, including X. epitropicalis and two undescribed species. Allopolyploidization between two 18-chromosome species occurred at least once 21-40 Mya, giving rise to the ancestor of all Xenopus species with 36, 72 or 108 chromosomes (Evans et al, 2004;Chain and Evans, 2006;Hellsten et al, 2007). Therefore, X. laevis and X. tropicalis are good animal models for understanding the process of genomic and chromosomal reorganization after WGD.…”