A genome-scale analysis for identification of genes required for growth or survival of
            <i>Haemophilus</i>
            <i>influenzae</i>

Akerley, Brian J.; Rubín, Eric J.; Novick, Veronica L.; Amaya, Kensey R.; Judson, Nicholas; Mekalanos, John J.

doi:10.1073/pnas.012602299

Cited by 335 publications

(248 citation statements)

References 30 publications

(8 reference statements)

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“…However, we caution that the gene sample analyzed here is relatively small, and thus our results should be reconfirmed when more data become available. In the future, it may also be possible to verify our results by comparing the essentiality of one-to-one orthologous genes from several bacterial species that have been subject to genome-wide gene deletion experiments (38,17,39). However, because of high incidences of horizontal gene transfer (40) and nonorthologous gene replacement (41) in prokaryotes, caution should be taken in such comparisons.…”

Section: Gene Expression Evolution Is Not the Cause Of Gene Essentialitymentioning

confidence: 99%

Null mutations in human and mouse orthologs frequently result in different phenotypes

Liao

Zhang

2008

Proc. Natl. Acad. Sci. U.S.A.

221

184

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One-to-one orthologous genes of relatively closely related species are widely assumed to have similar functions and cause similar phenotypes when deleted from the genome. Although this assumption is the foundation of comparative genomics and the basis for the use of model organisms to study human biology and disease, its validity is known only from anecdotes rather than from systematic examination. Comparing documented phenotypes of null mutations in humans and mice, we find that >20% of human essential genes have nonessential mouse orthologs. These changes of gene essentiality appear to be associated with adaptive evolution at the protein-sequence, but not gene-expression, level. Proteins localized to the vacuole, a cellular compartment for waste management, are highly enriched among essentiality-changing genes. It is probable that the evolution of the prolonged life history in humans required enhanced waste management for proper cellular function until the time of reproduction, which rendered these vacuole proteins essential and generated selective pressures for their improvement. If our gene sample represents the entire genome, our results would mean frequent changes of phenotypic effects of one-to-one orthologous genes even between relatively closely related species, a possibility that should be considered in comparative genomic studies and in making cross-species inferences of gene function and phenotypic effect.evolution ͉ mammals ͉ gene essentiality ͉ vacuole

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Section: Gene Expression Evolution Is Not the Cause Of Gene Essentialitymentioning

confidence: 99%

Null mutations in human and mouse orthologs frequently result in different phenotypes

Liao

Zhang

2008

Proc. Natl. Acad. Sci. U.S.A.

221

184

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“…The very idea that there are important genes whose functions are still obscure is quite unsettling as it reveals that there are still important gaps in our understanding of basic (micro)biology (9,10). Our recent study of the H.in¯uenzae proteome identi®ed 15`conserved hypothetical' proteins that were con®dently detected in aerobically grown cells (11) and whose genes were found to be essential in transposon mutagenesis studies (12). This prompted us to take a closer look at the expressed genes of H.in¯uenzae which were annotated as`hypothetical'.…”

Section: Introductionmentioning

confidence: 99%

Identification and functional analysis of 'hypothetical' genes expressed in Haemophilus influenzae

Kolker¹,

Makarova

Shabalina

et al. 2004

Nucleic Acids Research

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The progress in genome sequencing has led to a rapid accumulation in GenBank submissions of uncharacterized`hypothetical' genes. These genes, which have not been experimentally characterized and whose functions cannot be deduced from simple sequence comparisons alone, now comprise a signi®cant fraction of the public databases. Expression analyses of Haemophilus in¯uenzae cells using a combination of transcriptomic and proteomic approaches resulted in con®dent identi®ca-tion of 54`hypothetical' genes that were expressed in cells under normal growth conditions. In an attempt to understand the functions of these proteins, we used a variety of publicly available analysis tools. Close homologs in other species were detected for each of the 54`hypothetical' genes. For 16 of them, exact functional assignments could be found in one or more public databases. Additionally, we were able to suggest general functional characterization for 27 more genes (comprising~80% total). Findings from this analysis include the identi®cation of a pyruvate-formate lyase-like operon, likely to be expressed not only in H.in¯uenzae but also in several other bacteria. Further, we also observed three genes that are likely to participate in the transport and/or metabolism of sialic acid, an important component of the H.in¯uenzae lipo-oligosaccharide. Accurate functional annotation of uncharacterized genes calls for an integrative approach, combining expression studies with extensive computational analysis and curation, followed by eventual experimental veri®cation of the computational predictions.

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“…These problems can be overcome by integrating many taxonomically diverse gene essentiality datasets into the analysis with a focus on the biological functions that are conserved across multiple datasets. This approach has been applied previously using essentiality datasets from five different organisms [29], but now we expanded the study to the 13 currently available datasets [19,[30][31][32][33][34][35][36][37][38][39][40][41][42][43]. We began our analysis by comparing the lists of SEED functional roles associated with the essential genes in each of the 13 datasets to identify the biological functions that are conserved across multiple datasets.…”

Section: Gaining More From Gene Essentiality Datamentioning

confidence: 99%

Building the blueprint of life

Henry

Overbeek²,

Stevens

2010

Biotechnology Journal

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With recent breakthroughs in experimental microbiology making it possible to synthesize and implant an entire genome to create a living cell, the challenge of constructing a working blueprint for the first truly minimal synthetic organism is more important than ever. Here we review the significant progress made in the design and creation of a minimal organism. We discuss how comparative genomics, gene essentiality data, naturally small genomes, and metabolic modeling are all being applied to produce a catalogue of the biological functions essential for life. We compare the minimal gene sets from three published sources with functions identified in 13 existing gene essentiality datasets. We examine how genome-scale metabolic models have been applied to design a minimal metabolism for growth in simple and complex media. Additionally, we survey the progress of efforts to construct a minimal organism, either through implementation of combinatorial deletions in Bacillus subtilis and Escherichia coli or through the synthesis and implantation of synthetic genomes.

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A genome-scale analysis for identification of genes required for growth or survival of Haemophilus influenzae

Cited by 335 publications

References 30 publications

Null mutations in human and mouse orthologs frequently result in different phenotypes

Null mutations in human and mouse orthologs frequently result in different phenotypes

Identification and functional analysis of 'hypothetical' genes expressed in Haemophilus influenzae

Building the blueprint of life

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