Figure 6

Positive evolutionary selection analysis of HERC5. A, Neighbor-joining phylogenetic tree for progressive alignment of 13 different HERC5 species using constraint-based alignment tool (COBALT) for multiple protein sequences (Additional file 1: Figure S4). Branch lengths are proportional to the amount of inferred evolutionary changes. B and C, Selecton analysis for positive selection was performed using HERC5 sequences from human, chimpanzee, gorilla, marmoset, baboon, squirrel monkey, gibbon, horse, panda, sheep, cow, dog and cat. Evolutionary analysis for positive selection in HERC5 using various models of evolution where M8 and MEC allow for sites to evolve under positive selection and M7 and M8a models do not. (B) A plot of the Ka/Ks ratio at each codon in an alignment of HERC5 coding sequences is shown. Codons with Ka/Ks ratios >1 indicate positive selection, =1 neutral selection and <1 purifying selection. C, A plot showing the results of a Bayesian analysis approach to identify sites where Ka/Ks >1, mapped to the different HERC5 domains. Shown are the sites where Ka/Ks >1.5 and the 95% confidence interval is larger than 1; hence considered statistically significant. D, The HERC5 RLD was modeled using SWISS-MODEL (Swiss Institute of Bioinformatics: http://swissmodel.expasy.org/) and visualized and colored using DeepView/Swiss-PDBViewer, v4.0.1. The region corresponding to amino acids 2–103 is colored red. All other colors are arbitrary and used to highlight the different blades of the β-propeller structure. The inset numbers identify the different blades. “N” and “C” denote the amino- and carboxyl-termini respectively.