Comparative genomics, minimal gene-sets and the last universal common ancestor

• Published in: Nature reviews. Microbiology 2003-11, Vol.1 (2), p.127-136
• Main Author: Koonin, Eugene V.
• Format: Article
• Language: English
• Subjects: Bacteria - genetics; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biomedical and Life Sciences; Computational Biology; Eukaryotic Cells; Evolution, Molecular; Experimental methods; Genes, Essential; Genomics; Infectious Diseases; Life Sciences; Medical Microbiology; Microbiology; Parasitology; Proteins; Proteins - genetics; Proteins - metabolism; review-article; Virology
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/nrmicro751

Key Points A minimal set of genes that is necessary and sufficient for sustaining a functional cell can be delineated either by computational comparisons of microbial genomes or experimentally by knocking out genes in simple microbes. The minimal gene-set needs to be defined together with the environmental conditions under which these genes are sufficient to support a cell. For the most favourable conditions, with all nutrients provided and no environmental stress, computational and experimental approaches agree on 250–300 genes as the size of the minimal set. For most essential cellular functions, two or more unrelated or distantly related proteins have evolved; only ∼60 proteins — primarily those involved in translation and the basic aspects of transcription — are conserved in all cellular life-forms. Therefore, even for the same conditions, there can be many versions of the minimal gene-set. The reconstruction of ancestral life-forms is based on the principle of evolutionary parsimony: the simplest scenario is developed so as to reconcile the observed distribution of genes among species with the species tree. The size and composition of the reconstructed ancestral gene repertoires depend on relative rates of gene loss and horizontal gene-transfer, two phenomena that have been central to microbial evolution. The parsimony approach suggests that the last universal common ancestor (LUCA) of all extant life forms might have had as few as 500–600 genes. The gene set of LUCA that is derived in this fashion might resemble the minimal gene-set for a free-living prokaryote. However, arguments have also been made for a more complex LUCA. The experimental investigation of various versions of the minimal gene-set for cellular life and reconstructed ancestral life-forms might be an important research direction in the second and third decades of the twenty-first century. Comparative genomics, using computational and experimental methods, enables the identification of a minimal set of genes that is necessary and sufficient for sustaining a functional cell. For most essential cellular functions, two or more unrelated or distantly related proteins have evolved; only about 60 proteins, primarily those involved in translation, are common to all cellular life. The reconstruction of ancestral life-forms is based on the principle of evolutionary parsimony, but the size and composition of the reconstructed ancestral gene-repertoires depend on relative rates of gene loss and h