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Eukaryotic genomic origins, parasites, and the essential nature of mitochondria

Final Report Summary - EUKORIGINMIT (Eukaryotic genomic origins, parasites, and the essential nature of mitochondria)

Research within EUKORIGINMIT has made important contributions to understanding the evolution of eukaryotic cells. This includes the discovery that a two domains tree of life is a better-supported hypothesis than the classic three domains tree of life which previously appeared in textbooks. In the new two domains tree the basal split in life is between the Archaea and the Bacteria, with the eukaryotes, cells like our own, originating from within the Archaea. This research has received strong support from the discovery of new environmental Archaea that are more closely related to eukaryotes and which contain genes for proteins that were previously thought to be unique to eukaryotes. The broad impact of this work is demonstrated by the appearance of the new two domains tree in major University textbooks. Work studying lateral gene transfer has shown that the genomes of free-living and parasitic microbial eukaryotes are subject to frequent LGT from the bacteria they encounter in their habitats. This runs counter to some prevailing ideas that LGT is not an important force in eukaryotic evolution. Some of the transferred genes encode proteins that now play key roles in the biology of medically and economically important parasites. For example, Microsporidia are obligate intracellular parasites related to fungi that infect both immune-competent and immune-compromised humans and commercially important animals including fish, silkworms and honeybees. We have shown that nucleotide transport proteins (NTTs) acquired through LGT from bacteria, are now essential for supplying the energy and nucleotide building blocks needed for the growth and replication of Microsporidia inside infected host cells. The importance of NTTs in the biology of Microsporidia makes them excellent targets for therapeutic intervention against a group of parasites of increasing medical and economic importance. We also demonstrated that the cristae-deficient mitochondrion (mitosome) of the microsporidian Trachipleistophora hominis is the functional site of iron-sulphur cluster (ISC) assembly, which we suggest is now the sole and essential task of this organelle. A variety of techniques were used to demonstrate that mitosomes contain a complete pathway for [2Fe-2S] cluster biosynthesis that we biochemically reconstituted using purified recombinant mitosomal ISC proteins. Phylogenetic analyses provide strong evidence that the eukaryotic pathways for making essential Fe/S proteins are of mixed ancestry from Bacteria and Archaea. This mixed evolutionary history of the Fe/S-related proteins and pathways, and their strong conservation among highly reduced parasites, provides compelling evidence for the ancient chimeric ancestry of the eukaryotic cell.