Gene Transfers Shaped the Evolution of De Novo NAD + Biosynthesis in Eukaryotes

Abstract

NAD+ is an essential molecule for life, present in each living cell. It can function as an electron carrier or cofactor in redox biochemistry and energetics, and serves as substrate to generate the secondary messenger cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate. Although de novo NAD+ biosynthesis is essential, different metabolic pathways exist in different eukaryotic clades. The kynurenine pathway starting with tryptophan was most likely present in the last common ancestor of all eukaryotes, and is active in fungi and animals. The aspartate pathway, detected in most photosynthetic eukaryotes, was probably acquired from the cyanobacterial endosymbiont that gave rise to chloroplasts. An evolutionary analysis of enzymes catalyzing de novo NAD+ biosynthesis resulted in evolutionary trees incongruent with established organismal phylogeny, indicating numerous gene transfers. Endosymbiotic gene transfers probably introduced the aspartate pathway into eukaryotes and may have distributed it among different photosynthetic clades. In addition, several horizontal gene transfers substituted eukaryotic genes with bacterial orthologs. Although horizontal gene transfer is accepted as a key mechanism in prokaryotic evolution, it is supposed to be rare in eukaryotic evolution. The essential metabolic pathway of de novo NAD+ biosynthesis in eukaryotes was shaped by numerous gene transfers.

The sunlit microoxic niche of the archaeal eukaryotic ancestor comes to light

“…linking TCA and ETC), we investigated its de novo synthesis mechanisms (Figure 4). As expected, all Asgardaeota phyla were found to harbor the aspartate pathway 19 - a set of metabolic transformations that can occur in both presence or absence of oxygen 20 , and which are characteristic for most prokaryotes and the plastid-bearing eukaryotes (obtained through lateral gene transfer from their cyanobacterial endosymbiont) 18 . Surprisingly, Heimdallarchaeia presented in addition to the aspartate pathway the exclusively aerobic kynurenine one 21 (Figure 4), which is reported to be present in few bacterial groups and eukaryotes 18 .…”

“…As expected, all Asgardaeota phyla were found to harbor the aspartate pathway 19 - a set of metabolic transformations that can occur in both presence or absence of oxygen 20 , and which are characteristic for most prokaryotes and the plastid-bearing eukaryotes (obtained through lateral gene transfer from their cyanobacterial endosymbiont) 18 . Surprisingly, Heimdallarchaeia presented in addition to the aspartate pathway the exclusively aerobic kynurenine one 21 (Figure 4), which is reported to be present in few bacterial groups and eukaryotes 18 . The phylogenetic reconstruction and evolutionary history inferences showed that this pathway, which is considered to be present in the protoeukaryote ancestor 18 , was probably acquired by Heimdallarchaeia through lateral gene transfer from bacteria (Supplementary Figure S3).…”

“…As nicotinamide adenine dinucleotide (NAD + ) is an essential cofactor in redox biochemistry and energetics 16 (e.g. linking TCA and ETC), we investigated its de novo synthesis mechanisms ( Figure 4 ).…”

“…Surprisingly, Heimdallarchaeia presented in addition to the aspartate pathway the exclusively aerobic kynurenine one 19 ( Figure 4 ), which is reported to be present in few bacterial groups and eukaryotes 16 . The phylogenetic reconstruction and evolutionary history inferences showed that this pathway, which is considered to be present in the protoeukaryote ancestor 16 , was probably acquired by Heimdallarchaeia through lateral gene transfer from bacteria ( Supplementary Figure S3 ). As far as the authors are aware, Heimdallarchaeia are the first archaeal organisms with the aerobic kynurenine pathway.…”

The NAD+ salvage pathway modulates cancer cell viability via p73

“…NAD + has central roles in a variety of biological processes ranging from cellular metabolism and energy production to the regulation of enzymatic activities. 14 Accumulating evidence reveals that NAD + serves as a substrate for non-redox reactions, which are essential for diverse biological functions such as gene expression, Ca 2+ mobilization and cell death. Importantly, as mentioned above, NAD + serves as a key cofactor of SIRTs in removing the acetyl moiety from various proteins, and hence has a crucial role in regulating their activities.…”