Inst. f. Informatik   
Uni Leipzig

Bioinformatics Preprint 04-014

[Supplemental Material]

Molecular Evolution of Duplicated Ray Finned Fish HoxA Clusters:
Increased synonymous substitution rate and asymmetrical co-divergence of coding and non-coding sequences.

Günter P. Wagner, Kazuhiko Takahashi, Vincent Lynch, Sonja J. Prohaska, Claudia Fried, Peter F. Stadler, Chris T. Amemiya

Submitted for publication in:
J. Mol. Evol.

In this study the molecular evolution of duplicated HoxA genes in zebrafish and fugu has been investigated. All eighteen duplicated HoxA genes studied have a higher nonsynonymous substitution rate than the corresponding genes in either bichir or paddlefish, where these genes are not duplicated. Surprisingly, though, 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 neither be explained by changes in nucleotide composition nor 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 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. In fugu, the putative cis-regulatory elements of the b-paralog HoxA cluster diverge faster, while in zebrafish those of the a-paralog cluster diverge faster. Hence, we found evidence for a concerted asymmetric divergence of coding sequences on the same cluster as well as between coding and non-coding sequences. 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.

Ray Finned Fishes, HoxA Cluster

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