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This review focuses on microbes (viruses, bacteria, archaea) which developed in these prehistoric times and their roles during the later evolution of protists (eukaryotes). Among the different theories of life evolution, the author favors the theory of the RNA world as having been first. Over the past few decades, new molecular biological technologies and findings have changed the paradigm of mutation and selection as being the main driving force of biological evolution. Instead, microbes and microbe-derived genetic elements (e.g., plasmids, transposons) have been found to be capable of changing whole genomes and creating new species. Versatile RNA molecules have played important roles, such as regulating gene expression and affecting epigenetic changes, from primordial times up to the present. Microbes have been reported to show parasitic as well as mutualistic symbiotic relationships with their infected hosts. Examples of endosymbiogenesis are chloroplasts and mitochondria acting as new organelles, which facilitate photosynthesis and respiration within eukaryotic host cells. Considering the importance of these events, molecular mechanisms of photosynthesis and respiration are described in some detail in this review.<\/jats:p>","DOI":"10.3390\/ijms27198790","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:20:59Z","timestamp":1790781659000},"page":"8790","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microbes as Key Players During Evolution: I From the Beginnings to the Appearance of Eukaryotes"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1253-9145","authenticated-orcid":false,"given":"Volker","family":"Schirrmacher","sequence":"first","affiliation":[{"name":"Immune-Oncological Center Cologne (IOZK), D-50674 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"ref_1","unstructured":"Raven, P.H., Evert, R.F., and Eichhorn, S.E. 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