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Updated: Mar 10, 2026

A Bioinformatics Pipeline for Investigating Molecular Evolution and Gene Expression using RNA-seq
Published on: May 28, 2021
The evolution of function within the Nudix homology clan
John R Srouji1,2, Anting Xu3, Annsea Park2
1Plant and Microbial Biology Department, University of California, Berkeley, California, 94720.
The Nudix protein family, comprising over 80,000 domains, shows diverse functions from hydrolases to regulatory roles. Analysis reveals evolutionary insights into substrate specificity, particularly within Nudix pyrophosphohydrolases.
Area of Science:
- Biochemistry and Molecular Evolution
- Protein Domain Analysis
- Bioinformatics
Background:
- The Nudix homology clan is a large protein family found across all domains of life.
- These proteins exhibit diverse functions including enzymatic (pyrophosphohydrolases, isomerases, glycosylases) and non-enzymatic activities.
- Understanding the evolutionary trajectory of this vast functional diversity is crucial.
Purpose of the Study:
- To investigate the evolution of functional diversity within the Nudix protein family.
- To refine existing functional annotations and propose new ones based on experimental data.
- To identify structural features that explain the evolution of substrate specificity.
Main Methods:
- Literature-based assembly and analysis of experimental and structural data for 205 Nudix proteins.
- Correction and proposal of Gene Ontology annotations for Nudix proteins.
- Construction of structure-guided sequence alignments for Nudix domains.
- Phylogenetic analyses of Nudix protein domains.
Main Results:
- 53 Gene Ontology annotations were corrected, and 275 new annotations were proposed.
- A structure-guided sequence alignment of 78 Nudix proteins was created, followed by an alignment of 347 curated Nudix domains.
- A specific loop region in Nudix pyrophosphohydrolases was identified as a potential driver of functional evolution and substrate specificity.
- Phylogenetic analyses indicated general monophyly with functional grouping, alongside instances of homoplasy.
Conclusions:
- The Nudix family exhibits remarkable functional diversity driven by evolutionary processes.
- Structural analysis, particularly of a key loop region, provides insights into the evolution of substrate specificity in Nudix pyrophosphohydrolases.
- Phylogenetic relationships support functional clustering and highlight evolutionary convergence within the Nudix clan.
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