Melani Martín de Hijas Villalbabioinformatica.uab.cat/base/documents/Genomics/portfolio...Melani...
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The “minimum cell” Genomics The “minimum cell” Melani Martín de Hijas Villalba
Transcript of Melani Martín de Hijas Villalbabioinformatica.uab.cat/base/documents/Genomics/portfolio...Melani...
The “minimum cell”
Genomics
The “minimum cell”
Melani Martín de Hijas Villalba
Minimum cell =
Minimal gene set cell
Genomics
The “minimum cell”
Smallest possible group of genes sufficient to sustain a functioning cellular life form under the most favorable conditions imaginable, that is, in the presence of a full complement of essential nutrients and in the absence of environmental stress
Genomics
The “minimum cell”
Genome size
Coding genes
Genomics
The “minimum cell”
Mycoplasmas were proposed by Morowitz (1984) as models for understanding the principles of life
Podar et al., 2008
Comparative genomics Saturation tansposon mutagenesis Saturation tansposon mutagenesis + next- generation sequencing Antisense RNA Single gene specific mutagenesis
Essential genes
Genomics
The “minimum cell”
Juhas et al., 2011
nº insertion sites gene length
Comparative genomic analysis
240 orthologous genes + 22 nonorthologous genes - 6 parasite-specific genes
256 genes
Genomics
The “minimum cell”
*Mushegian and Koonin, 1996
Mycoplasma genitalium (468 genes) Vs Haemophilus influenzae (1703 genes)*
Mycoplasma genitalium (480 genes) Vs Micoplasma pneumoniae (677 genes) (1999) Transposon mutagenesis and sequencing 351 ortholog genes without disruption
Bottom-up approach
Mycoplasma mycoides in Mycoplasma capricolum JCVI-syn1.0 1077947 bp in vivo homologous recombination in yeast
Genomics
The “minimum cell”
‐ 20 polymorphism* ‐ 4 watermarks (WM) ‐ 4-kb deletion (94D) ‐ Elements for grow ‐ Genome transplantation Gibson et al., 2010
Top-down approach
Bacillus subtilis
Genomics
The “minimum cell”
Tanaka et al., 2013
JCVI-syn3.0
Genomics
The “minimum cell”
Mycoplasma mycoides in Mycoplasma capricolum Hypothetical minimal genome of 8 segments 531 kbp 438 proteins 35 annotated RNAs
Applications
Provide a plausible theory for the origin of life Advance knowledge of biological replication (hypothesis testing) Develop new technical applications Biomedical applications (drugs discovery and delivery) Generate useful microorganisms (to produce pharmaceuticals and fuels) Add new functions that are absent in biological cells.
Genomics
The “minimum cell”
Conclusion
The minimal cell concept appears simple at first glance but becomes more complex upon close inspection Redundant genes for essential functions are scored as nonessential in comparative genomic analysis It seems to be more appropriate to consider not a rigid minimal gene set but rather a minimal set of functional niches (NOD) A minimal genome determined under laboratory conditions should reveal a core set of environment independent functions that are necessary and sufficient for life Artificial cells can be create by Bottom-up or Top-down approaches The generation of artificial cells have a lot of applications
Genomics
The “minimum cell”
Bibliography
Podar M, Anderson I, et al., A genomic analysis of the archaeal system Ignicoccus hospitalis-Nanoarchaeum equitans. Genome Biol. 2008;9(11):R158. doi: 10.1186/gb-2008-9-11-r158. Epub 2008 Nov 10. Anthony C Forster and George M Church. Towards synthesis of a minimal cell. Molecular Systems Biology. 2006.doi:10.1038/msb4100090 D. G. Gibson et al., Creation of a bacterial cell controlled by a chemically synthesized genome. Science 329, 52–56, 2010. Clyde. A. Hutchison III et al., Global transposon mutagenesis and a minimal Mycoplasma genome. Science 286, 2165–2169, 1999. Clyde A. Hutchison III et al., Design and synthesis of a minimal bacterial genome. Science, VOL 351 ISSUE 6280, 2016 M. Juhas, D. R. Reuß, B. Zhu, F. M. Commichau, Bacillus subtilis and Escherichia coli essential genes and minimal cell factories after one decade of genome engineering. Microbiology 160, 2341–2351, 2014. doi: 10.1099/mic.0.079376-0 Mario Juhas, Leo Eberl and John I. Glass. Essence of life: essential genes of minimal genomes. Trends in Cell Biology, October 2011, Vol. 21, No. 10. doi:10.1016/j.tcb.2011.07.005 Eugene V. Koonin., HOW MANY GENES CAN MAKE A CELL: TheMinimal-Gene-Set Concept. Annu. Rev. Genomics Hum. Genet. 2000. 01:99–116 Tanaka, K., Henry, C. S., Zinner, J. F., Jolivet, E., Cohoon, M. P., Xia, F., Bidnenko, V., Ehrlich, S. D., Stevens, R. L. & Noirot, P. Building the repertoire of dispensable chromosome regions in Bacillus subtilis entails major refinement of cognate large-scale metabolic model. Nucleic Acids Res 41, 687–699, 2013.
Genomics
The “minimum cell”
Genomics
The “minimum cell”
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