Evolution and classification of P-loop kinases and related proteins

Area of Science:

• Biochemistry and Molecular Biology
• Evolutionary Biology
• Bioinformatics

Background:

• P-loop NTPase fold proteins are crucial enzymes involved in numerous cellular processes.
• Understanding the evolutionary history of P-loop-containing kinases is essential for deciphering their diverse functions.

Purpose of the Study:

• To reconstruct the evolutionary history and classification of P-loop-containing kinases.
• To identify distinct protein families and their ancestral origins within the P-loop NTPase fold.

Main Methods:

• Comparative analysis of protein sequences and structures.
• Standard phylogenetic methods, sequence/structural signature analysis, and similarity-based clustering.
• Reconstruction of evolutionary events and ancestral states.

Main Results:

• Identified approximately 40 distinct protein families within the P-loop kinase class, many phosphorylating nucleosides, nucleotides, and sugars.
• Reconstructed the early evolution, including splits into kinase, GTPase, and ATPase lineages, with evidence for multiple P-loop kinases in the last universal common ancestor.
• Revealed significant evolution through bacterial and archaeal families, horizontal gene transfer in eukaryotes, and the emergence of the DxTN superfamily in selfish replicons.

Conclusions:

• Kinases and related proteins form a monophyletic group within the P-loop NTPase fold, with diverse catalytic capabilities.
• Eukaryotic kinases largely originated from bacteria via horizontal gene transfer, including from endosymbionts.
• The study provides a framework for characterizing newly identified kinase families and their functions.