Special Topics in Computational Biology Lecture 9: Genome Evolution & Simulation Joey (Yi) Zhou



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Special Topics in Computational Biology Lecture 9: Genome Evolution & Simulation

  • Joey (Yi) Zhou

  • Department of Biology, NYU


Genome Size (prokaryotes)

  • Bacterial genome: 6105~more than 107

  • Smallest known: Mollicutes genitalium (470 protein coding genes, 3 rRNA genes, 33 tRNA genes)

  • Prokaryotes genome sizes are roughly proportional to gene numbers.

  • Processes affect bacterial genome size:

  • Gene duplication, small-scale deletions and insertions, transpositions, horizontal transfer, loss of genes in parasitic lines, etc.



Minimal Genome Size – Analytic approach

  • Mushegian and Koonin, 1996:

  • By comparison of complete bacterial genomes:



Minimal Genome Size – Experimental approach

  • Itaya, 1995:

  • Knock-out 79 randomly selected genes from Bacillus subtilis:

  • Only 6 lethal, 73 are dispensable  7.5% (6/79) of genome indispensable.

  • B.subtilis genome: 4.2106bp  7.5% = 3.2105bp

  • Average gene size is 1.25Kb, so the minimal genome size  254 genes.



Quote…

  • Hayden, 1999:

  • One day a scientist will drop gene number 297 into a test tube, then number 298, then 299… and presto: what was not alive a moment ago will be alive now. The creature will be as simple as life can be. But it will still be life. And humans will have made it, in an ordinary glass tube, from off-the-shelf chemicals…



Genome Size (eukaryotes)

  • Eukayotic genome: 8.8106~ 6.91011

  • Smallest known include: Saccharomyces cerevisiae and other fungi

  • Eukaryotes genome sizes are NOT proportional to gene numbers or anatomical complexity.



Global Increase in Genome Size

  • Polyploidization (whole genome duplication):

  • Allopolyploidy: combination of genetically distinct chromosome sets. (Wheat…)

  • Autopolyploidy: multiplication of one basic set of chromosomes. (Goldfish, rose…)

  • Autopolyploidy Cryptopolyploidy

  • Regional duplication:



The Yeast Genome: Tetraploidy or regional duplications?

  • 54 non-overlapping duplicated regions are found in the yeast genome. (Wolfe and Shields, 1997)

  • 50 of the duplicated regions have maintained the same orientation with respect to centromere

  • No triplicated regions are found, while 7 are expected with 55 successive duplications based on Poisson distribution.

  • It’s more likely to be the result of tetraploidy than successive regional duplications.



Gene Number & Order Evolution in a Duplicated Genome



Repetitive Structure of Eukaryotic Genome

  • Eukaryotic genomes contain various degrees of repetitive structure: satellites, micro/mini-satellites, retrotransposons, retrovirus, etc.

  • Repetitive sequence size correlates with genome size:



Mechanisms for Regional Increase in Genome Size

  • Duplicative transposition

  • Unequal crossing-over

  • Replication slippage

  • Gene amplification (rolling circle replication)



Gene Duplication

  • duplication of a part of the gene:

  • domain/internal sequence duplication  enhance function, novel function by new combination

  • duplication of a complete gene (gene family)

  • invariant duplication: dose repetitions,

  • variant duplication: new functions.

  • duplication of a cluster of genes



Internal Gene Duplication



Complete Gene Duplication

  • Invariant duplication:

  • RNA specifying genes: Number of tRNA and rRNA correlates with genome size.

  • Variant duplication:

  • Opsins:



Gene Loss

  • Duplicated genes  unprocessed pseudogenes.

  • Single-copy genes devoid of selection pressure  unitary pseudogenes.

  • Loss of L-gulono--lactone oxidase in humans, guinea pigs, etc. comparing to other vertebrates: the enzyme at the terminal step of synthesizing L-ascorbic acid (vitamin C).



Chromosome Rearrangement



Gene Order Rearrangements

  • Sankoff, 1992: Estimate the number of gene order rearrangement events.

  • E=D+R

  • E: evolutionary edit distance;

  • D: deletion distance;

  • R: Rearrangement distance.

  • Three geometrical procedures:

  • deletion, combine, inversion.

  • D = number of segments removed (deletion);

  • R = number of inversion.

  • Problems:

  • NP-complete, Gene duplication, etc.



Gene Order Rearrangements in Bacteria



Other Interesting Structures in Genomes

  • Chirochores:

  • Skew:

  • If there is no strand-bias, then

  • However, Lobry (1996) found considerable deviation from no strand-bias assumption. The spatial distribution of the skews switched direction at the origin and terminus of replication.



Other Interesting Structures in Genomes

  • Chirochores:

  • Why chirochores?

  • Possible hypothesis: Mutational bias associated with replication direction.



Other Interesting Structures in Genomes

  • Isochores: blocks of genomic DNA with different GC content.

  • When vertebrate genomic DNA is randomly sheared into fragments 30-100kb in size and the fragments are separated by their base composition, the fragments cluster into a small number of classes, with nearly discrete GC content distribution. Therefore, the vertebrate genomes are mosaic of ischores.

  • Origin of isochores: Selection result? Mutational result?



How to Study Genome Evolution?

  • In silico evolution simulation (Coming up by Dr.Archisman Rudra)

  • In laboratory evolution experiment:-- ‘Test tube evolution catches time in a bottle’

  • Richard Lenski’s group, Michigan State University have been maintaining different E.coli strains (both wildtype and mutants) since 1991 (average 6.6 generations per day).

  • Evolution records: fitness, morphology, sequence divergence, mutation rate…



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