Mitochondrial translation systems that break the rules

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Mitochondrial translation systems that break the rulesEukaryotes (i.e. organisms such as animals, plants, and fungi whose cells carry a nucleus) evolved from a mixture of various life forms. Best known is the mitochondrion, the powerhouse of the eukaryotic cell, which goes back to a bacterial symbiont that was acquired by the ancestor of eukaryotes about one billion years ago. This organelle still possesses its own small genome and its own machineries for basic molecular processes including protein synthesis. However, in most eukaryotes, the bacterial ancestry of mitochondria is barely perceptible, since this organelle is exceptionally fast-evolving, often resulting in dramatic changes of basic molecular processes. This has earned mitochondria the reputation as Nature's most advanced evolutionary laboratory'. The objective of our research program is to investigate such innovations at the molecular-genetics and genomics levels, and to understand how they came about. The current focus of our research program is on novelties in mitochondrial protein synthesis, notably two extraordinary phenomena. 1. Invention' of new genetic codes. We have shown previously how mitochondria of yeast have invented new translation-code variants, changing rules how gene sequences are translated into protein. Our bioinformatics tools predict additional similar cases across yeast relatives. We propose to validate these new predictions biochemically, and to investigate their molecular and evolutionary underpinning.2. Translational jumping. We have found recently that a group of yeast (Magnusiomycetes) does not follow conventional rules for translating genes via messenger RNA into protein. Their mitochondrial genes contain numerous short sequence insertions (byps') that normally would block translation. The machinery in Magnusiomycetes mitochondria ignores' these inserts by jumping over them. We propose to investigate the evolutionary origin of byps, their genetic mobility, and the biochemical mechanism of translational bypassing.Investigation of novelties discovered in simple species such as yeasts has been often the first step towards recognizing similar phenomena in more complex species such as humans or plants. Further, insights into unconventional protein synthesis might teach us how to control this process with benefits for human health, agriculture and environment. Requiring a trans-disciplinary research approach, the proposed projects will be highly suited for training students and highly-qualified research personnel.