Molecular Evolution of Duplicated Ray Finned Fish HoxA Clusters: Increased Synonymous Substitution Rate and Asymmetrical Co-divergence of Coding and Non-coding Sequences

Wagner, G.P., Takahashi, K., Lynch, V., Prohaska, S.J., Fried, C., Stadler, P.F., and Amemiya, C.
Journal of molecular evolution   60(5): 665-676 (Journal)
Registered Authors
Amemiya, Chris
Duplicated HoxA genes; Ray finned fish; Synonymous substitution rate; Zebrafish; Fugu; Coding sequences; Non-coding sequences; Asymmetrical co-divergence
MeSH Terms
  • Animals
  • Base Sequence
  • Computational Biology
  • Databases, Nucleic Acid
  • Evolution, Molecular*
  • Fishes/genetics*
  • Genes, Duplicate/genetics*
  • Genes, RAG-1
  • Homeodomain Proteins/genetics*
  • Molecular Sequence Data
  • Mutation/genetics
  • Open Reading Frames/genetics
  • Phylogeny*
  • Sequence Analysis, DNA
  • Species Specificity
15983874 Full text @ J. Mol. Evol.
In this study the molecular evolution of duplicated HoxA genes in zebrafish and fugu has been investigated. All 18 duplicated HoxA genes studied have a higher non-synonymous substitution rate than the corresponding genes in either bichir or paddlefish, where these genes are not duplicated. The higher rate of evolution is not due solely to a higher non-synonymous-to-synonymous rate ratio but to an increase in both the non-synonymous as well as the synonymous substitution rate. The synonymous rate increase can be explained by a change in base composition, codon usage, or mutation rate. We found no changes in nucleotide composition or codon bias. Thus, we suggest that the HoxA genes may experience an increased mutation rate following cluster duplication. In the non-Hox nuclear gene RAG1 only an increase in non-synonymous substitutions could be detected, suggesting that the increased mutation rate is specific to duplicated Hox clusters and might be related to the structural instability of Hox clusters following duplication. The divergence among paralog genes tends to be asymmetric, with one paralog diverging faster than the other. In fugu, all b-paralogs diverge faster than the a-paralogs, while in zebrafish Hoxa-13a diverges faster. This asymmetry corresponds to the asymmetry in the divergence rate of conserved non-coding sequences, i.e., putative cis-regulatory elements. These results suggest that the 5' HoxA genes in the same cluster belong to a co-evolutionary unit in which genes have a tendency to diverge together.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes