RRC ID 52713
Author Ochi H, Kawaguchi A, Tanouchi M, Suzuki N, Kumada T, Iwata Y, Ogino H.
Title Co-accumulation of cis-regulatory and coding mutations during the pseudogenization of the Xenopus laevis homoeologs six6.L and six6.S.
Journal Dev Biol
Abstract Common models for the evolution of duplicated genes after genome duplication are subfunctionalization, neofunctionalization, and pseudogenization. Although the crucial roles of cis-regulatory mutations in subfunctionalization are well-documented, their involvement in pseudogenization and/or neofunctionalization remains unclear. We addressed this issue by investigating the evolution of duplicated homeobox genes, six6.L and six6.S, in the allotetraploid frog Xenopus laevis. Based on a comparative expression analysis, we observed similar eye-specific expression patterns for the two loci and their single ortholog in the ancestral-type diploid species Xenopus tropicalis. However, we detected lower levels of six6.S expression than six6.L expression. The six6.S enhancer sequence was more highly diverged from the orthologous enhancer of X. tropicalis than the six6.L enhancer, and showed weaker activity in a transgenic reporter assay. Based on a phylogenetic analysis of the protein sequences, we observed greater divergence between X. tropicalis Six6 and Six6.S than between X. tropicalis Six6 and Six6.L, and the observed mutations were reminiscent of a microphthalmia mutation in human SIX6. Misexpression experiments showed that six6.S has weaker eye-enlarging activity than six6.L, and targeted disruption of six6.L reduced the eye size more significantly than that of six6.S. These results suggest that enhancer attenuation stimulates the accumulation of hypomorphic coding mutations, or vice versa, in one duplicated gene copy and facilitates pseudogenization. We also underscore the value of the allotetraploid genome of X. laevis as a resource for studying latent pathogenic mutations.
Volume 427(1)
Pages 84-92
Published 2017-7-1
DOI 10.1016/j.ydbio.2017.05.004
PII S0012-1606(16)30549-8
PMID 28501477
MeSH Amino Acid Sequence Animals Animals, Genetically Modified Base Sequence Embryo, Nonmammalian / embryology Embryo, Nonmammalian / metabolism Enhancer Elements, Genetic / genetics Evolution, Molecular Gene Duplication Gene Expression Regulation, Developmental Genes, Duplicate / genetics Homeodomain Proteins / classification Homeodomain Proteins / genetics* In Situ Hybridization Mutation / genetics* Phylogeny Protein Isoforms / genetics Pseudogenes / genetics Regulatory Sequences, Nucleic Acid / genetics* Retina / embryology Retina / metabolism Sequence Homology, Amino Acid Sequence Homology, Nucleic Acid Xenopus Proteins / genetics* Xenopus laevis / embryology Xenopus laevis / genetics*
IF 2.936
Times Cited 3
Xenopus tropicalis Xenopus tropicalis