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Expansion of the human mitochondrial proteome by intra- and inter-compartmental protein duplication.

Szklarczyk R, Huynen MA - Genome Biol. (2009)

Bottom Line: These duplications significantly expanded carbohydrate metabolism, the protein import machinery and the calcium regulation of mitochondrial activity.Gene duplication relaxes this constraint on the cellular location, allowing nascent proteins to be relocalized to other compartments.We estimate that the mitochondrial proteome expanded at least 50% since the common ancestor of human and yeast.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Molecular and Biomolecular Informatics, NCMLS, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands. radek@cmbi.ru.nl

ABSTRACT

Background: Mitochondria are highly complex, membrane-enclosed organelles that are essential to the eukaryotic cell. The experimental elucidation of organellar proteomes combined with the sequencing of complete genomes allows us to trace the evolution of the mitochondrial proteome.

Results: We present a systematic analysis of the evolution of mitochondria via gene duplication in the human lineage. The most common duplications are intra-mitochondrial, in which the ancestral gene and the daughter genes encode mitochondrial proteins. These duplications significantly expanded carbohydrate metabolism, the protein import machinery and the calcium regulation of mitochondrial activity. The second most prevalent duplication, inter-compartmental, extended the catalytic as well as the RNA processing repertoire by the novel mitochondrial localization of the protein encoded by one of the daughter genes. Evaluation of the phylogenetic distribution of N-terminal targeting signals suggests a prompt gain of the novel localization after inter-compartmental duplication. Relocalized duplicates are more often expressed in a tissue-specific manner relative to intra-mitochondrial duplicates and mitochondrial proteins in general. In a number of cases, inter-compartmental duplications can be observed in parallel in yeast and human lineages leading to the convergent evolution of subcellular compartments.

Conclusions: One-to-one human-yeast orthologs are typically restricted to their ancestral subcellular localization. Gene duplication relaxes this constraint on the cellular location, allowing nascent proteins to be relocalized to other compartments. We estimate that the mitochondrial proteome expanded at least 50% since the common ancestor of human and yeast.

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Evolution of mitochondrial localization for the branched-chain-amino-acid aminotransferases family. (a) Gene tree generated by PhyML [70] for vertebrates, yeast and outgroup species that speciated before duplication events. Bootstrap values (100 repetitions) are shown on the internal branches. Proteins surrounded by an oval are localized to mitochondria; loss of the mitochondrial localization is marked by a cross. (b) Clustal W [71] alignment of the amino-terminal region of orthologs. The predicted targeting sequences are highlighted in blue. Abbreviations: hs. Homo sapiens; mm, Mus musculus; dm, Drosophila melanogaster; dr, Dano rerio; lm, L. major; sc, S. cerevisiae.
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Figure 4: Evolution of mitochondrial localization for the branched-chain-amino-acid aminotransferases family. (a) Gene tree generated by PhyML [70] for vertebrates, yeast and outgroup species that speciated before duplication events. Bootstrap values (100 repetitions) are shown on the internal branches. Proteins surrounded by an oval are localized to mitochondria; loss of the mitochondrial localization is marked by a cross. (b) Clustal W [71] alignment of the amino-terminal region of orthologs. The predicted targeting sequences are highlighted in blue. Abbreviations: hs. Homo sapiens; mm, Mus musculus; dm, Drosophila melanogaster; dr, Dano rerio; lm, L. major; sc, S. cerevisiae.

Mentions: While tracing the history of duplications that extend the mitochondrial proteome, one can imagine, in the most drastic scenario, that independent duplications in unrelated lineages with subsequent parallel relocalizations to mitochondria could lead to a convergent evolution in the mitochondrial protein content. Several paralogs present this unusual evolutionary pattern (Table 3). For example, branched-chain-amino-acid aminotransferase underwent duplication at the root of vertebrates, in addition to an independent event in yeast as a result of whole genome duplication. In both species one copy is targeted to the mitochondria (BCAT2 in human), the other is cytosolic (BCAT1). In the case of this gene family, the analysis of distant orthologs for the presence/absence of the targeting signal sheds light on the likely ancestral localization. Using MitoProt II [39] and TargetP [38] the signal can be detected in the fly sequence as well as Leishmania major orthologs, suggesting that the ancestral BCAT protein was part of the mitochondrial proteome in the ancestor of human and yeast (Figure 4).


Expansion of the human mitochondrial proteome by intra- and inter-compartmental protein duplication.

Szklarczyk R, Huynen MA - Genome Biol. (2009)

Evolution of mitochondrial localization for the branched-chain-amino-acid aminotransferases family. (a) Gene tree generated by PhyML [70] for vertebrates, yeast and outgroup species that speciated before duplication events. Bootstrap values (100 repetitions) are shown on the internal branches. Proteins surrounded by an oval are localized to mitochondria; loss of the mitochondrial localization is marked by a cross. (b) Clustal W [71] alignment of the amino-terminal region of orthologs. The predicted targeting sequences are highlighted in blue. Abbreviations: hs. Homo sapiens; mm, Mus musculus; dm, Drosophila melanogaster; dr, Dano rerio; lm, L. major; sc, S. cerevisiae.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3091328&req=5

Figure 4: Evolution of mitochondrial localization for the branched-chain-amino-acid aminotransferases family. (a) Gene tree generated by PhyML [70] for vertebrates, yeast and outgroup species that speciated before duplication events. Bootstrap values (100 repetitions) are shown on the internal branches. Proteins surrounded by an oval are localized to mitochondria; loss of the mitochondrial localization is marked by a cross. (b) Clustal W [71] alignment of the amino-terminal region of orthologs. The predicted targeting sequences are highlighted in blue. Abbreviations: hs. Homo sapiens; mm, Mus musculus; dm, Drosophila melanogaster; dr, Dano rerio; lm, L. major; sc, S. cerevisiae.
Mentions: While tracing the history of duplications that extend the mitochondrial proteome, one can imagine, in the most drastic scenario, that independent duplications in unrelated lineages with subsequent parallel relocalizations to mitochondria could lead to a convergent evolution in the mitochondrial protein content. Several paralogs present this unusual evolutionary pattern (Table 3). For example, branched-chain-amino-acid aminotransferase underwent duplication at the root of vertebrates, in addition to an independent event in yeast as a result of whole genome duplication. In both species one copy is targeted to the mitochondria (BCAT2 in human), the other is cytosolic (BCAT1). In the case of this gene family, the analysis of distant orthologs for the presence/absence of the targeting signal sheds light on the likely ancestral localization. Using MitoProt II [39] and TargetP [38] the signal can be detected in the fly sequence as well as Leishmania major orthologs, suggesting that the ancestral BCAT protein was part of the mitochondrial proteome in the ancestor of human and yeast (Figure 4).

Bottom Line: These duplications significantly expanded carbohydrate metabolism, the protein import machinery and the calcium regulation of mitochondrial activity.Gene duplication relaxes this constraint on the cellular location, allowing nascent proteins to be relocalized to other compartments.We estimate that the mitochondrial proteome expanded at least 50% since the common ancestor of human and yeast.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Molecular and Biomolecular Informatics, NCMLS, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands. radek@cmbi.ru.nl

ABSTRACT

Background: Mitochondria are highly complex, membrane-enclosed organelles that are essential to the eukaryotic cell. The experimental elucidation of organellar proteomes combined with the sequencing of complete genomes allows us to trace the evolution of the mitochondrial proteome.

Results: We present a systematic analysis of the evolution of mitochondria via gene duplication in the human lineage. The most common duplications are intra-mitochondrial, in which the ancestral gene and the daughter genes encode mitochondrial proteins. These duplications significantly expanded carbohydrate metabolism, the protein import machinery and the calcium regulation of mitochondrial activity. The second most prevalent duplication, inter-compartmental, extended the catalytic as well as the RNA processing repertoire by the novel mitochondrial localization of the protein encoded by one of the daughter genes. Evaluation of the phylogenetic distribution of N-terminal targeting signals suggests a prompt gain of the novel localization after inter-compartmental duplication. Relocalized duplicates are more often expressed in a tissue-specific manner relative to intra-mitochondrial duplicates and mitochondrial proteins in general. In a number of cases, inter-compartmental duplications can be observed in parallel in yeast and human lineages leading to the convergent evolution of subcellular compartments.

Conclusions: One-to-one human-yeast orthologs are typically restricted to their ancestral subcellular localization. Gene duplication relaxes this constraint on the cellular location, allowing nascent proteins to be relocalized to other compartments. We estimate that the mitochondrial proteome expanded at least 50% since the common ancestor of human and yeast.

Show MeSH