Limits...
Evolutionary and genetic analyses of mitochondrial translation initiation factors identify the missing mitochondrial IF3 in S. cerevisiae.

Atkinson GC, Kuzmenko A, Kamenski P, Vysokikh MY, Lakunina V, Tankov S, Smirnova E, Soosaar A, Tenson T, Hauryliuk V - Nucleic Acids Res. (2012)

Bottom Line: However, unlike the translation system of its bacterial ancestors, mitochondrial translation is limited to just a few mRNAs, mainly coding for components of the respiratory complex.The classical bacterial initiation factors (IFs) IF1, IF2 and IF3 are universal in bacteria, but only IF2 is universal in mitochondria (mIF2).Our results highlight the lineage-specific nature of mitochondrial translation and emphasise that comparative analyses among diverse taxa are essential for understanding whether generalizations from model organisms can be made across eukaryotes.

View Article: PubMed Central - PubMed

Affiliation: University of Tartu, Institute of Technology, Tartu, Estonia. gemma.atkinson@ut.ee

ABSTRACT
Mitochondrial translation is essentially bacteria-like, reflecting the bacterial endosymbiotic ancestry of the eukaryotic organelle. However, unlike the translation system of its bacterial ancestors, mitochondrial translation is limited to just a few mRNAs, mainly coding for components of the respiratory complex. The classical bacterial initiation factors (IFs) IF1, IF2 and IF3 are universal in bacteria, but only IF2 is universal in mitochondria (mIF2). We analyse the distribution of mitochondrial translation initiation factors and their sequence features, given two well-propagated claims: first, a sequence insertion in mitochondrial IF2 (mIF2) compensates for the universal lack of IF1 in mitochondria, and secondly, no homologue of mitochondrial IF3 (mIF3) is identifiable in Saccharomyces cerevisiae. Our comparative sequence analysis shows that, in fact, the mIF2 insertion is highly variable and restricted in length and primary sequence conservation to vertebrates, while phylogenetic and in vivo complementation analyses reveal that an uncharacterized S. cerevisiae mitochondrial protein currently named Aim23p is a bona fide evolutionary and functional orthologue of mIF3. Our results highlight the lineage-specific nature of mitochondrial translation and emphasise that comparative analyses among diverse taxa are essential for understanding whether generalizations from model organisms can be made across eukaryotes.

Show MeSH
Phylogenetic tree of mitochondrial IF3 (mIF3), Aim23p and bacterial IF3. The tree is a MrBayes consensus tree, generated from 156 aligned amino acids. The standard deviation of split frequencies at the end of the MrBayes run was 0.015. Branch support, GI numbers and substitutions per site are indicated as per Figure 1. The Aim23p clade is indicated with a dashed box.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3401457&req=5

gks272-F3: Phylogenetic tree of mitochondrial IF3 (mIF3), Aim23p and bacterial IF3. The tree is a MrBayes consensus tree, generated from 156 aligned amino acids. The standard deviation of split frequencies at the end of the MrBayes run was 0.015. Branch support, GI numbers and substitutions per site are indicated as per Figure 1. The Aim23p clade is indicated with a dashed box.

Mentions: Phylogenetic analysis of the full data set comprising IF3/mIF3/cpIF3 and Aim23p shows that the Aim23p sequences group with other fungi (Supplementary Figure S2). Although this has only weak support in the full IF3 tree (51% MLBP), phylogenetic analysis of a cut-down IF3 data set with the longest branched protist IF3 sequences removed and more sites included has very strong support for the monophyly of Aim23p and fungal mIF3s (1.0 BIPP, 98% MLBP; Figure 3). Thus, although the position of Aim23p within fungi has no significant support, it clearly groups with fungi, and the most parsimonious explanation is that Aim23p is in fact the previously unidentified mIF3 orthologue. The inability to find significant mIF3 hits across fungi using BlastP alone is probably due to the short length of IF3 and its highly biased amino acid composition. IF3 is enriched in charged amino acids, particularly lysine; E. coli IF3, human mIF3 and S. cerevisiae Aim23p contain 11.7, 10.4 and 14.9% lysine, respectively (Supplementary Table S3). Schizosaccharomyces pombe mIF3 is also surprisingly enriched in serine (12.4%). The bias in lysine composition in IF3 and the IF2 insertions may reflect the role of these proteins in binding negatively charged RNA; enrichment of lysine and other charged amino acids is a feature of ribosomal proteins (40).Figure 3.


Evolutionary and genetic analyses of mitochondrial translation initiation factors identify the missing mitochondrial IF3 in S. cerevisiae.

Atkinson GC, Kuzmenko A, Kamenski P, Vysokikh MY, Lakunina V, Tankov S, Smirnova E, Soosaar A, Tenson T, Hauryliuk V - Nucleic Acids Res. (2012)

Phylogenetic tree of mitochondrial IF3 (mIF3), Aim23p and bacterial IF3. The tree is a MrBayes consensus tree, generated from 156 aligned amino acids. The standard deviation of split frequencies at the end of the MrBayes run was 0.015. Branch support, GI numbers and substitutions per site are indicated as per Figure 1. The Aim23p clade is indicated with a dashed box.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3401457&req=5

gks272-F3: Phylogenetic tree of mitochondrial IF3 (mIF3), Aim23p and bacterial IF3. The tree is a MrBayes consensus tree, generated from 156 aligned amino acids. The standard deviation of split frequencies at the end of the MrBayes run was 0.015. Branch support, GI numbers and substitutions per site are indicated as per Figure 1. The Aim23p clade is indicated with a dashed box.
Mentions: Phylogenetic analysis of the full data set comprising IF3/mIF3/cpIF3 and Aim23p shows that the Aim23p sequences group with other fungi (Supplementary Figure S2). Although this has only weak support in the full IF3 tree (51% MLBP), phylogenetic analysis of a cut-down IF3 data set with the longest branched protist IF3 sequences removed and more sites included has very strong support for the monophyly of Aim23p and fungal mIF3s (1.0 BIPP, 98% MLBP; Figure 3). Thus, although the position of Aim23p within fungi has no significant support, it clearly groups with fungi, and the most parsimonious explanation is that Aim23p is in fact the previously unidentified mIF3 orthologue. The inability to find significant mIF3 hits across fungi using BlastP alone is probably due to the short length of IF3 and its highly biased amino acid composition. IF3 is enriched in charged amino acids, particularly lysine; E. coli IF3, human mIF3 and S. cerevisiae Aim23p contain 11.7, 10.4 and 14.9% lysine, respectively (Supplementary Table S3). Schizosaccharomyces pombe mIF3 is also surprisingly enriched in serine (12.4%). The bias in lysine composition in IF3 and the IF2 insertions may reflect the role of these proteins in binding negatively charged RNA; enrichment of lysine and other charged amino acids is a feature of ribosomal proteins (40).Figure 3.

Bottom Line: However, unlike the translation system of its bacterial ancestors, mitochondrial translation is limited to just a few mRNAs, mainly coding for components of the respiratory complex.The classical bacterial initiation factors (IFs) IF1, IF2 and IF3 are universal in bacteria, but only IF2 is universal in mitochondria (mIF2).Our results highlight the lineage-specific nature of mitochondrial translation and emphasise that comparative analyses among diverse taxa are essential for understanding whether generalizations from model organisms can be made across eukaryotes.

View Article: PubMed Central - PubMed

Affiliation: University of Tartu, Institute of Technology, Tartu, Estonia. gemma.atkinson@ut.ee

ABSTRACT
Mitochondrial translation is essentially bacteria-like, reflecting the bacterial endosymbiotic ancestry of the eukaryotic organelle. However, unlike the translation system of its bacterial ancestors, mitochondrial translation is limited to just a few mRNAs, mainly coding for components of the respiratory complex. The classical bacterial initiation factors (IFs) IF1, IF2 and IF3 are universal in bacteria, but only IF2 is universal in mitochondria (mIF2). We analyse the distribution of mitochondrial translation initiation factors and their sequence features, given two well-propagated claims: first, a sequence insertion in mitochondrial IF2 (mIF2) compensates for the universal lack of IF1 in mitochondria, and secondly, no homologue of mitochondrial IF3 (mIF3) is identifiable in Saccharomyces cerevisiae. Our comparative sequence analysis shows that, in fact, the mIF2 insertion is highly variable and restricted in length and primary sequence conservation to vertebrates, while phylogenetic and in vivo complementation analyses reveal that an uncharacterized S. cerevisiae mitochondrial protein currently named Aim23p is a bona fide evolutionary and functional orthologue of mIF3. Our results highlight the lineage-specific nature of mitochondrial translation and emphasise that comparative analyses among diverse taxa are essential for understanding whether generalizations from model organisms can be made across eukaryotes.

Show MeSH