1. Department of Biology, NYU
Special Topics in Computational Biology Lecture 9: Genome Evolution & Simulation
Joey (Yi) Zhou
Department of Biology, NYU
©Joey Zhou, 2002
12/2/2018

2. 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.
©Joey Zhou, 2002
12/2/2018

3. Minimal Genome Size – Analytic approach
Mushegian and Koonin, 1996:
By comparison of complete bacterial genomes:
Translation
Replication
Transcription
Recombination and DNA repair
Chaperone-like proteins
Anaerobic metabolism
Lipid or cofactor biosynthesis
Transmembrane transporter
Some unknown function
E. coli
H.influenzae
M.genitalium
1,146
1,129
889 18 10
239 1
[Overlapping orthologous genes (239)] + [non-orthologous gene displacement] – [genes specific to parasitic bacteria or of functional redundancy] = 256 genes
©Joey Zhou, 2002
12/2/2018

4. 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.
©Joey Zhou, 2002
12/2/2018

5. 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…
©Joey Zhou, 2002
12/2/2018

6. 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.
©Joey Zhou, 2002
12/2/2018

7. 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:
Mutations, translocations,
rearrangements
©Joey Zhou, 2002
12/2/2018

8. 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.
©Joey Zhou, 2002
12/2/2018

9. Gene Number & Order Evolution in a Duplicated Genome
ABCDEFGHIJKLM
a b c d e f g h i j k l m
NOPQRSTUVWXYZ
n o p q r s t u v w x y z
26 genes, 2 chomosomes
26 genes, 2 chomosomes
Tetraploidization
ABCDEFGHIJKLM
a b c d e f g h i j k l m
NOPQRSTUVWXYZ
52 genes, 4 chomosomes
n o p q r s t u v w x y z
Gene loss
AB DEF HI KLM
AB DEF H
s t v w x y
b c e g h j k m
Translocation
b c e g h j k m
N PQ TUV X Z
N PQ TUV X Z
n o p r s t v w x y
n o p r
I KLM
Crossing over
bc E’F H
s t v w x y
AB D e’ g h j k m
N PQ TUV X Z
36 genes, 4 chomosomes
n o p r
I KLM
©Joey Zhou, 2002
12/2/2018

10. 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:
Gorrila gorilla
Symphalangus syndactylus
Heterochromatin (*109bp)
Pan troglodites
Homo sapiens
Hylobates muelleri
Genome size (*109bp)
©Joey Zhou, 2002
12/2/2018

11. Mechanisms for Regional Increase in Genome Size
Duplicative transposition
Unequal crossing-over
Replication slippage
Gene amplification (rolling circle replication)
©Joey Zhou, 2002
12/2/2018

12. 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
©Joey Zhou, 2002
12/2/2018

13. Internal Gene Duplication5’ 1 2 3 4 5 6 3’
Ancestral trypsinogen gene
Deletion 1 6’ 5’ 3’
Thr Ala Ala Gly
4 fold duplication + addition of spacer sequence 1 6’ 5’ 3’
Internal duplications + addition of intron sequence
Spacer: Gly … 1 1 2 3 4 5 6 7 37 38 39 40 41 6’ 3’ 5’
Antifreeze glycoprotein gene
©Joey Zhou, 2002
12/2/2018

14. Complete Gene Duplication
Invariant duplication:
RNA specifying genes: Number of tRNA and rRNA correlates with genome size.
Variant duplication:
Opsins:
X-linked
autosomal
Trichromatic
Human female
Human male
Dichromatic
(color blind) or
New world monkey
female
male
©Joey Zhou, 2002
12/2/2018

15. 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).
©Joey Zhou, 2002
12/2/2018

16. Chromosome Rearrangement
(Introduction to Genetic Analysis. 7th ed)
Griffiths, Anthony J.F.; Gelbart, William M.; Miller, Jeffrey H.; Lewontin, Richard C.
©Joey Zhou, 2002
12/2/2018

17. 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.
©Joey Zhou, 2002
12/2/2018

18. Gene Order Rearrangements in Bacteria
(Watanabe et al. 1997)
©Joey Zhou, 2002
12/2/2018

19. 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.
Skew diagram of Bacillus subtilis
©Joey Zhou, 2002
12/2/2018

20. Other Interesting Structures in Genomes
Chirochores:
Why chirochores?
Possible hypothesis: Mutational bias associated with replication direction. C A T G
Vectorial representation of the genomic DNA sequence from Escherichia coli (Lobry, 1996).
©Joey Zhou, 2002
12/2/2018

21. Other Interesting Structures in Genomes
Isochores: blocks of genomic DNA with different GC content.
When vertebrate genomic DNA is randomly sheared into fragments kb 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?
©Joey Zhou, 2002
12/2/2018

22. 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…
©Joey Zhou, 2002
12/2/2018