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Three-dimensional (3D) protein modeling and bioinformatics revealed that orf19.2500 is a conserved mitochondrial protein, structurally similar to, but functionally diverged from, the squalene\/phytoene synthases family. The\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>albicans<\/jats:italic>\n                    orf19.2500 is distinguished by 3 evolutionarily acquired stretches of amino acid inserts, absent from all other eukaryotes except a small number of ascomycete fungi. Biochemical assays showed that orf19.2500 is required for the assembly and activity of the\n                    <jats:underline>N<\/jats:underline>\n                    A\n                    <jats:underline>D<\/jats:underline>\n                    H\n                    <jats:underline>u<\/jats:underline>\n                    biquinone oxidoreductase Complex I (CI) of the respiratory electron transport chain (ETC) and was thereby named\n                    <jats:italic>NDU1<\/jats:italic>\n                    .\n                    <jats:italic>NDU1<\/jats:italic>\n                    is essential for respiration and growth on alternative carbon sources, important for immune evasion, required for virulence in a mouse model of hematogenously disseminated candidiasis, and for potentiating resistance to antifungal drugs. Our study is the first report on a protein that sets the\n                    <jats:italic>Candida<\/jats:italic>\n                    -like fungi phylogenetically apart from all other eukaryotes, based solely on evolutionary \u201cgain\u201d of new amino acid inserts that are also the functional hub of the protein.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3000957","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T13:39:17Z","timestamp":1615815557000},"page":"e3000957","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["An evolutionarily diverged mitochondrial protein controls biofilm growth and virulence in Candida 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