A comprehensive phylogenetic analysis of deadenylases

Abstract

Deadenylases catalyze the shortening of the poly(A) tail at the messenger ribonucleic acid (mRNA) 3'-end in eukaryotes. Therefore, these enzymes influence mRNA decay, and constitute a major emerging group of promising anti-cancer pharmacological targets. Herein, we conducted full phylogenetic analyses of the deadenylase homologs in all available genomes in an effort to investigate evolutionary relationships between the deadenylase families and to identify invariant residues, which probably play key roles in the function of deadenylation across species. Our study includes both major Asp-Glu-Asp-Asp (DEDD) and exonuclease-endonuclease-phospatase (EEP) deadenylase superfamilies. The phylogenetic analysis has provided us with important information regarding conserved and invariant deadenylase amino acids across species. Knowledge of the phylogenetic properties and evolution of the domain of deadenylases provides the foundation for the targeted drug design in the pharmaceutical industry and modern exonuclease anti-cancer scientific research.

Keywords: deadenylases; evolution; molecular modelling; phylogenesis.

Figure 1

Phylogenetic tree of DEDD deadenylases. Bootstrap values (>50%) are shown at the nodes. The length of the tree branches reflects evolutionary distance. The scale bar at the upper left represents the length of amino acid substitutions per position. To minimize confusion, we used the protein names as described in Goldstrohm and Wickens; the UniProt 5-letter codes were used for the species names. The proteins derived from metazoa are shown in red, from viridiplantae in green, from fungi in orange and from protozoa in yellow.

Figure 2

Phylogenetic tree of EEP deadenylases. Bootstrap values above 50% are shown at the nodes. The length of the tree branches depicts evolutionary distance. The scale bar at the upper left represents the length of amino acid substitutions per site. To minimize confusion, we used the protein names as described in Goldstrohm and Wickens; the UniProt 5-letter codes were used for the species names. The proteins derived from metazoa are shown in red, from viridiplantae in green, from fungi in orange and from protozoa in yellow.

Figure 3

Results of the rate shift analysis for the 19 DEDD proteins. Sites with blue and red highlight correspond to those with slower and faster evolutionary rate, respectively. Sites with entirely blue or red highlight represent amino acid sites with the same evolutionary rate in all families, but with significantly slower or faster rates compared to the average of all sites, respectively.

Figure 4

Sequence logos of the motifs identified in deadenylase protein sequences. (A) DEDD, numbered according to the human PARN nuclease domain (PDB code 2A1R) and (B) EEP, numbered according to the human CNOT6 nuclease domain. The height of each letter is relative to the frequency of the corresponding residue at that position, and the letters are ordered such as the most frequent is on the top. The invariant catalytic residues that define each superfamily are indicated with dots.