It is proposed that the pre-cellular stage of biological evolution, including the Last Universal Common Ancestor (LUCA) of modern cellular life forms, occurred within networks of inorganic compartments that hosted a diverse mix of virus-like genetic elements. This viral model of cellular origin recapitulates the early ideas of J.B.S. Haldane, sketched in his 1928 essay on the origin of life. However, unlike in Haldane's day, there is substantial empirical support for this scenario from three major lines of evidence provided by comparative genomics: (i) the lack of homology among the core components of the DNA replication systems between the two primary lines of descent of cellular life forms, archaea and bacteria, (ii) the similar lack of homology between the enzymes of lipid biosynthesis in conjunction with distinct membrane chemistries in archaea and bacteria, and (iii) the spread of several viral hallmark genes, which encode proteins with key functions in viral replication and morphogenesis, among numerous and extremely diverse groups of viruses, in contrast to their absence in cellular life forms. Under the viral model of pre-cellular evolution, the key elements of cells including the replication apparatus, membranes, molecular complexes involved in membrane transport and translocation, and others originated as components of virus-like entities. This model alleviates, at least in part, the challenge of the emergence of the immensely complex organization of modern cells.
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