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Vol. 93, Issue 19, 10268-10273, September 17, 1996
National Center for Biotechnology Information, National Library of
Medicine, National Institutes of Health, Bethesda, MD 20894
Communicated by Clyde Hutchinson, University of North Carolina,
Chapel Hill, NC, May 17, 1996 (received for review March 11, 1996)
The recently sequenced genome of the parasitic bacterium
Mycoplasma genitalium contains only 468 identified
protein-coding genes that have been dubbed a minimal gene complement
[Fraser, C. M., Gocayne, J. D., White, O., Adams, M. D., Clayton, R. A., et al. (1995) Science 270,
397-403]. Although the M. genitalium gene complement
is indeed the smallest among known cellular life forms, there is no
evidence that it is the minimal self-sufficient gene set. To derive
such a set, we compared the 468 predicted M. genitalium
protein sequences with the 1703 protein sequences encoded by the other
completely sequenced small bacterial genome, that of Haemophilus
influenzae. M. genitalium and H. influenzae belong to two ancient bacterial lineages, i.e., Gram-positive and
Gram-negative bacteria, respectively. Therefore, the genes that are
conserved in these two bacteria are almost certainly essential for
cellular function. It is this category of genes that is most likely to
approximate the minimal gene set. We found that 240 M.
genitalium genes have orthologs among the genes of H.
influenzae. This collection of genes falls short of comprising the minimal set as some enzymes responsible for intermediate steps in
essential pathways are missing. The apparent reason for this is the
phenomenon that we call nonorthologous gene displacement when the same
function is fulfilled by nonorthologous proteins in two organisms. We
identified 22 nonorthologous displacements and supplemented the set of
orthologs with the respective M. genitalium genes. After
examining the resulting list of 262 genes for possible functional
redundancy and for the presence of apparently parasite-specific genes,
6 genes were removed. We suggest that the remaining 256 genes are close
to the minimal gene set that is necessary and sufficient to sustain the
existence of a modern-type cell. Most of the proteins encoded by the
genes from the minimal set have eukaryotic or archaeal homologs but
seven key proteins of DNA replication do not. We speculate that the
last common ancestor of the three primary kingdoms had an RNA genome.
Possibilities are explored to further reduce the minimal set to model a
primitive cell that might have existed at a very early stage of life
evolution.
0027-8424/96/9310268-6/0
Evolution
A minimal gene set for cellular life derived by comparison of
complete bacterial genomes
*
To whom reprint requests should be addressed at: National Center
for Biotechnology Information, National Library of Medicine, Building
38A, National Institutes of Health, Bethesda, MD 20894. e-mail:
koonin{at}ncbi.nlm.nih.gov.
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