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

Nature Reviews Microbiology volume 1, pages 127–136 (2003)Cite this article

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.

Abstract

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 horizontal gene-transfer. The present estimate suggests a simple last universal common ancestor with only 500–600 genes.

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Figure 1: How to derive minimal gene-sets by genome comparison: a scheme.
Figure 2: Protein functions encoded in the mimimal gene-set.
Figure 3: Gene conservation (phyletic spread) in the set of essential genes of Bacillus subtilis, the computational minimal gene-set, and the complete set of conserved genes.
Figure 4: Parsimonious evolutionary scenarios for two genes.
Figure 5: Dependence of the number of genes in a reconstructed last universal common ancestor on the relative rates of gene loss and horizontal gene transfer.
Figure 6: Essential functions for different versions of the last universal common ancestor: glycolysis and gluconeogenesis.

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Acknowledgements

I gratefully acknowledge my intellectual debt to A. Mushegian (minimal gene-set analysis) and B. Mirkin (reconstruction of evolutionary scenarios) and constructive discussions with F. Doolittle and P. Forterre on the nature of the last universal common ancestor. I thank A. Osterman for useful discussions on minimal gene-sets and for providing me with his data prior to publication.

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  1. National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, NIH Building 38A, 8600 Rockville Pike, Bethesda, 20894, Maryland, USA

    Eugene V. Koonin

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FURTHER INFORMATION

Kyoto Encyclopedia of Genes and Genomes

NCBI COGs database

NCBI Entrez Genome database

The Tree of Life Web Project

TIGR Genome Projects Database

Glossary

ESSENTIAL GENE

A gene for which knockout is lethal under certain conditions.

ORTHOLOGUES

Homologous genes in different species that originate from the same ancestral gene in the last common ancestor of the species compared.

NON-ORTHOLOGOUS GENE DISPLACEMENT

Displacement of a gene responsible for a particular biological function in a certain set of species by a non-orthologous (unrelated or paralogous) gene in a different set of species.

PHYLETIC PATTERN

The pattern of presence or absence (representation by orthologues) of a gene in different lineages across the species tree.

SYNTHETIC LETHALS

Genes for which simultaneous knockout is lethal, whereas individual knockouts are viable.

SPECIES TREE

A phylogenetic tree that represents evolutionary relationships between species as a whole, as opposed to phylogenetic trees for individual genes.

EVOLUTIONARY PARSIMONY

A methodological approach in evolutionary biology that aims to explain an observed distribution of character states (for example, the phyletic pattern of a gene in a species tree) by postulating the minimal number of events in the course of evolution that could have led to that distribution.

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Koonin, E. Comparative genomics, minimal gene-sets and the last universal common ancestor. Nat Rev Microbiol 1, 127–136 (2003). https://doi.org/10.1038/nrmicro751

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