Episodic evolution of a eukaryotic NADK repertoire of ancient provenance.

Oliver Vickman,Albert Erives,Stéphanie Bertrand

doi:10.1371/journal.pone.0220447

Abstract

NAD kinase (NADK) is the sole enzyme that phosphorylates nicotinamide adenine dinucleotide (NAD+/NADH) into NADP+/NADPH, which provides the chemical reducing power in anabolic (biosynthetic) pathways. While prokaryotes typically encode a single NADK, eukaryotes encode multiple NADKs. How these different NADK genes are all related to each other and those of prokaryotes is not known. Here we conduct phylogenetic analysis of NADK genes and identify major clade-defining patterns of NADK evolution. First, almost all eukaryotic NADK genes belong to one of two ancient eukaryotic sister clades corresponding to cytosolic (“cyto”) and mitochondrial (“mito”) clades. Secondly, we find that the cyto-clade NADK gene is duplicated in connection with loss of the mito-clade NADK gene in several eukaryotic clades or with acquisition of plastids in Archaeplastida. Thirdly, we find that horizontal gene transfers from proteobacteria have replaced mitochondrial NADK genes in only a few rare cases. Last, we find that the eukaryotic cyto and mito paralogs are unrelated to independent duplications that occurred in sporulating bacteria, once in mycelial Actinobacteria and once in aerobic endospore-forming Firmicutes. Altogether these findings show that the eukaryotic NADK gene repertoire is ancient and evolves episodically with major evolutionary transitions.

Highlights

Nicotinamide adenine dinucleotide (NAD) is a dinucleotide cofactor essential to all living cells [1,2,3,4,5,6,7]
Our results show that NAD kinase (NADK) genes from all domains of life possess a potent phylogenetic signal in the genes themselves and in the series of duplications associated with major clade-defining events in cellular evolution
We find that the ancient cytosolic and mitochondrial forms of NADK were already present as sister paralogs in latest eukaryotic common ancestor (LECA)

Summary

Introduction

Nicotinamide adenine dinucleotide (NAD) is a dinucleotide cofactor essential to all living cells [1,2,3,4,5,6,7]. NAD’s adenine nucleotide holds one bit of information read by enzymes that recognize the absence (dot underlined hydroxyl group above) or presence of a phosphate group at the 2’ ribose carbon (dot underlined phosphate group below) This phosphorylation site is far removed from the nicotinamide base that serves as the electron-carrying moiety and is functionally independent of NAD’s redox state. We find that eukaryotic NADK gene evolution is episodic having been sensitive to major evolutionary transitions since the duplication of an NADK gene in early eukaryotic evolution This ancient duplication established two clades of enzymes that ancestrally corresponded to cytosolic (“cyto”-clade) and mitochondrial (“mito”-clade) forms that are maintained in plants, most animals, and some protist groups. These analyses show that there is a robust phylogenetic signal in the NADK sequences and in the particular repertoires of NADK genes

Results

Discussion

Materials and methods