Phylogenetic Reconstruction Shows Independent Evolutionary Origins of Mitochondrial Transcription Factors from an Ancient Family of RNA Methyltransferase Proteins

Abstract

Here, we generate a robust phylogenetic framework for the rRNA adenine N(6)-methyltransferase (RAMTase) protein family that shows a more ancient and complex evolutionary history within the family than previously reported. RAMTases occur universally by descent across the three domains of life, and typical orthologs within the family perform methylation of the small subunits of ribosomal RNA (rRNA). However, within the RAMTase family, two different groups of mitochondrial transcription factors, mtTFB1 and mtTFB2, have evolved in eukaryotes through neofunctionalization. Previous phylogenetic analyses have suggested that mtTFB1 and mtTFB2 comprise sister clades that arose via gene duplication, which occurred sometime following the endosymbiosis event that produced the mitochondrion. Through dense and taxonomically broad sampling of RAMTase family members especially within bacteria, we found that these eukaryotic mitochondrial transcription factors, mtTFB1 and mtTFB2, have independent origins in phylogenetically distant clades such that their divergence most likely predates the last universal common ancestor of life. The clade of mtTFB2s comprises orthologs in Opisthokonts and the clade of mtTFB1s includes orthologs in Amoebozoa and Metazoa. Thus, we clearly demonstrate that the neofunctionalization producing the transcription factor function evolved twice independently within the RAMTase family. These results are consistent with and help to elucidate outcomes from prior experimental studies, which found that some members of mtTFB1 still perform the ancestral rRNA methylation function, and the results have broader implications for understanding the evolution of new protein functions. Our phylogenetic reconstruction is also in agreement with prior studies showing two independent origins of plastid RAMTases in Viridiplantae and other photosynthetic autotrophs. We believe that this updated phylogeny of RAMTases should provide a robust evolutionary framework for ongoing studies to identify and characterize the functions of these proteins within diverse organisms.Electronic supplementary materialThe online version of this article (10.1007/s00239-018-9842-z) contains supplementary material, which is available to authorized users

A consensus view of the proteome of the last universal common ancestor

“…The Molecular Function Gene Ontology terms associated with the LUCA largely confirm what previous analyses have proposed or determined about the LUCA and, more broadly, early life forms. For example, the translation process is well known to be ancient (Freeland et al, 1999 ; Goldman et al, 2010 ) and many of the proteins involved in translation machinery appear to predate the LUCA (Fournier & Alm, 2015 ; Fournier et al, 2012 ; Harris & Goldman, 2018 ). A corollary to the influential RNA world hypothesis (Gilbert, 1986 ; Visser, 1984 ) is that the translation system evolved within the context of an RNA‐based genetic system (Freeland et al, 1999 ).…”

The draft nuclear genome sequence and predicted mitochondrial proteome of Andalucia godoyi, a protist with the most gene-rich and bacteria-like mitochondrial genome

“…AgDMT1 is (weakly) predicted to be targeted to mitochondria, and phylogenetic analysis shows that this protein is part of a broad clade of mtTFB1 and alphaproteobacterial DMT sequences identified by Harris and Goldman [93]. The presence of a characteristic motif found in conventional DMTs (PPPKV, positions 189-193 in the Andalucia protein) strongly suggests that the Andalucia protein functions as a DMT, as do some mtTFB1s [93]. In other ribosomal systems, both prokaryotic and eukaryotic cytosol as well as organelles, this protein is responsible for dimethylation of adjacent A residues in the 3′-terminal helix of small subunit (SSU) rRNA, corresponding to positions A1457 and A1458 in the Andalucia mitochondrial counterpart.…”

“…We found no evidence of a mtTFA homolog, whereas a mtTFB query retrieved two Andalucia homologs, AgDMT1 and AgDMT2, both of which have a dimethyltransferase (DMT) domain, as do both yeast [91] and human [92] mitochondrial mtTFBs. AgDMT1 is (weakly) predicted to be targeted to mitochondria, and phylogenetic analysis shows that this protein is part of a broad clade of mtTFB1 and alphaproteobacterial DMT sequences identified by Harris and Goldman [93]. The presence of a characteristic motif found in conventional DMTs (PPPKV, positions 189-193 in the Andalucia protein) strongly suggests that the Andalucia protein functions as a DMT, as do some mtTFB1s [93].…”

Scaling laws in enzyme function reveal a new kind of biochemical universality

“…To identify consensus enzyme function predictions for the LUCA, the results of eight previously published LUCA genome studies ( 35 – 42 ) were mapped onto clusters within the EggNOG database ( 43 ). LUCA genome predictions from all eight studies were mapped onto UniProt accessions ( 44 ), as in the LUCApedia database ( 16 ).…”