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Part I: Modeling cells 1. Why do you need to know the minimum number of genes needed to specify a cell in order to model a cell? 2. What are the

two general approaches taken to try to estimate the "minimal genome." 3. What is the minimal number of genes estimated by both approaches? 4. Go to http://genomebiology.biomedcentral.com/articles/10.1186/gb-2001-2-2-comment2002 • Scroll down to "A model organism with a minimal genome?" ● How large is the M. genitalium genome and how many proteins does it encode? Scroll down to "Can the minimal genome be defined?" Why will it be difficult to ever define a minimal genome? What determines whether a gene is essential or dispensable? Scroll down to "The theoretical minimal genome." How many genes do Haemophilus influenzae and M. genitalium have in common? • Scroll down to "An experimental approach" How many genes did they identify in M. genitalium that were apparently dispensable? • How many genes did they estimate are dispensable? • How do they interpret their finding that 100 of the essential genes are of unknown function? Scroll down to "Comparing many more genomes." What tool did they use to compare genes in 21 different species? • Why are COGs a more sensitive way to identify orthologous genes? How many genes were in common between all 21 species? What are the three reasons the authors suggest for the failure to identify an acceptable minimal genome by this approach? 5. Now go to http://www.pnas.org/content/103/2/425.full What is the new estimate for the minimal number of genes? • Scroll down to "Discussion." What was the key procedural improvement in this project? How many genes for hypothetical proteins and proteins of unknown function are essential?

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