Gregory Nature Rev. Genet. 6:699, 2005

1
Contribution of repetitive sequences to genome
expansion
Composition of human genome
Repeated sequences comprise 45 of total human
genome !!
Gregory Nature Rev. Genet. 6699, 2005 textbooks
2
Repetitive Elements May Comprise Over Two-Thirds
of the Human Genome
- used highly sensitive de novo strategy,
P-clouds, that searches for clusters of
high-abundance oligonucleotides that are related
in sequence space (oligo clouds)
de Koning PloS Genet. 7 e1002384, 2011
3
Transposons retrotransposons

• autonomous mobile elements that invade genomes
  and spread copies of themselves
• - over time, they typically accumulate
  mutations degenerate

DNA-mediated transposition - mobile element
encodes transposaseenzyme enabling integration
into host genome
Conservative
Replicative
Fig. 7.1
4
RNA-mediated transposition
- mobile retroelement encodes reverse
transcriptase
eg SINES, LINES
short long interspersed repetitive elements

• in human genome, Alu repeats derived from 7SL
  RNA gene

- also tRNA-derived (MIR repeats)
Fig. 7.1
5
Possible evolutionary consequences of
transposition events (p.349-353)
1. Increase in genome size
2. Promotes major DNA rearrangements may
affect gene structure or expression
- region between 2 TEs may be moved during
transposition
- impact on synteny?
3. Increased mutation rate may improve survival
under adverse conditions?
eg. antibiotic resistance genes on TEs in
bacteria, genomic reorganization events in plants
under environmental stress
6
Selfish DNA - especially in eukaryotic genomes
- playground for evolution
- creation of new genes, reshuffling existing ones
- rich source of paleontological info
- tools (markers) for medical genetic
population studies
Fig. 8.15
7
Relationship between transposon content and
eukaryotic genome size
- in lungfish, maybe massive amplification of
TEs followed by a long period with a very low
rate of sequence removal of decayed TEs
Metcalfe et al. Mol. Biol. Evol. 293529, 2012
8
Bacterial and archaebacterial genomes
Fig. 8.1
Possible explanations for species that are
outliers?
9
Molecular archaeology of the E.coli genome
4.6 Mbp
Transposition events (IS elements)
Horizontal gene transfer
Lawrence Ochman PNAS 959413, 1998
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Bacterial speciation is likely to be driven by a
high rate of horizontal transfer, which
introduces novel genes, confers beneficial
phenotypic capabilities, and permits the rapid
exploitation of competitive environments.
lac operon - ability to use milk sugar lactose as
carbon source
new niche for E.coli in mammalian colon
Ochman Nature 405 299, 2000
11
Yersinia pestis
The genome of the bacterium that causes plague
is highly dynamic and scarred by genes acquired
from other organisms.
Parkhill Nature 413523, 2001
Gene acquisition and decay
- lateral transfer of genes from other bacteria
viruses
eg surface antigens, virulence factors involved
in pathogenicity against both mammals and insects
Y. pestis has 149 pseudogenes
reductive evolution during colonization of new
niche
Genome fluidity
- inversion/translocation of chromosomal segments
- intragenomic recombination at IS element sites
12
Bacterial genomes have bias for G on leading
strand of bidirectional replication fork
- replication error differences between leading
and lagging DNA strands
Correlation between mutation rate chromosomal
location in bacteria?
For 3rd position of codons as well as
intergenic...
Fig. 8.27
13
Wide variation in GC content among bacterial
genomes
consequences for codon usage patterns?
Fig.8.26
Fig. 8.29
14
Extensive gene gain associated with adaptive
evolution of poxviruses
20 genomes compared (including smallpox
vaccinia)
disproportionately high proportion of genes
in orthopox clade are under positive selection
eg. genes important for host-parasite
co-evolution
McLysaght PNAS 10015655, 2003
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SPECULATIONS ON EVOLUTION OF EARLY LIFE-FORMS
Joyce Nature 418214, 2002
16
RNA world hypothesis
- first primitive living systems had RNA genome
Supported by multifunctional nature of
present-day RNA
- codes for proteins
- produces proteins
- carries out replication
- can act as catalyst
ribozymes - self-cleaving, self-slicing,
self-elongation
BUT DNA more stable for storing information (
DNA repair systems)
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Post-progressive Darwinian evolution
- origin of multicellular life environment
driven diversification
- most (but not all) mutations neutral
- those fixed by selection improve fitness only
for specific environmental conditions
Progressive Darwinian evolution
Origin of cellular life, communal web-of-life?
Strong selective advantage if able to propagate
info efficient production of useful proteins
Replication, transcription translation machinery
similar in all life-forms
Period of rapid mutation, increased accuracy
efficiency of info transfer gene organization
regulation
Pre-Darwinian evolution
Without self-replication, no entities to evolve
through natural selection
Doolittle Brown PNAS 916721, 1994
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Experimental evolution in vitro
SELEX iterated cycles of selection
amplification of sequences
Bittker Curr Opin Chem Biol 6367, 2002
19
Test-tube evolution of ribozyme
- selection for improved cleavage of DNA oligomer
substrate
- pool of 1013 molecules
- 140 nt (brown) randomly mutated so 5 chance
not wt sequence at any given position
The pool of variants was challenged such that
only those molecules that could catalyze the
cleavage of a DNA oligomer substrate (black box)
would be allowed to reproduce.
- after 9 rounds of selection reproduction, 4
mutations (pink sites) predominant
Freeman Fig. 16.5
Beaudry Joyce Science 257613, 1992
20
Experimental evolution in vivo
Comparison of positions of orthologous genes in
Mycoplasma Haemophilus
Fig.8.22
Papdopoulos, PNAS 963807, 1999
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