Gregory Nature Rev. Genet. 6:699, 2005 & textbooks

Repeated sequences comprise ~ 45% of total human genome !!Composition of human genome

Contribution of repetitive sequences to genome expansion

“Repetitive Elements May Comprise Over Two-Thirds of the Human Genome”

de Koning PloS Genet. 7: e1002384, 2011

- used “highly sensitive de novo strategy, P-clouds, that searches for clusters of high-abundance oligonucleotides that are related in sequence space (oligo ‘‘clouds’’)”

DNA-mediated transposition - mobile element encodes transposaseenzyme enabling

integration into host genome

Conservative Replicative

Fig. 7.1

Transposons & retrotransposons

- autonomous mobile elements that invade genomes and spread copies of themselves

- over time, they typically accumulate mutations & degenerate

eg SINES, LINES

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

Fig. 7.1

short & long interspersed repetitive elements

- also tRNA-derived (MIR repeats) …

- mobile retroelement encodes reverse transcriptaseRNA-mediated transposition

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…

“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

Metcalfe et al. Mol. Biol. Evol. 29:3529, 2012

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]”

Fig. 8.1

Bacterial and archaebacterial genomes

Possible explanations for species that are outliers?

“Molecular archaeology of the E.coli genome”

Lawrence & Ochman PNAS 95:9413, 1998

Horizontal gene transferTransposition events (IS elements)

4.6 Mbp

Ochman Nature 405: 299, 2000

“Bacterial speciation is likely to be driven by a high rate of horizontaltransfer, which introduces novel genes, confers beneficial phenotypiccapabilities, and permits the rapid exploitation of competitive environments”.

new niche for E.coli in mammalian colonlac operon - ability to use milk sugar lactose as carbon source

Parkhill Nature 413:523, 2001

Yersinia pestis

“The genome of the bacterium that causes plague is highly dynamic and scarred by genes acquired from other organisms”.

Genome fluidity- inversion/translocation of chromosomal segments- intragenomic recombination at IS element sites

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

“reductive evolution” during colonization of new nicheY. pestis has 149 pseudogenes

Bacterial genomes have bias for G on leading strand ofbidirectional replication fork

- replication error differences between leading and lagging DNA strands

Fig. 8.27

Correlation between mutation rate & chromosomal location in bacteria?For 3rd position of codons as well as intergenic...

Fig.8.26Fig. 8.29

Wide variation in GC content among bacterial genomes

consequences for codon usage patterns?

“Extensive gene gain associated with adaptive evolution of poxviruses”

McLysaght PNAS 100:15655, 2003

20 genomes compared(including smallpox & vaccinia)

“disproportionately highproportion of genes inorthopox clade are under positive selection”

eg. genes important for host-parasite co-evolution

Joyce Nature 418:214, 2002

SPECULATIONS ON EVOLUTION OF EARLY LIFE-FORMS

- codes for proteins

- produces proteins

- carries out replication

- can act as catalyst

BUT … DNA more stable for storing information (& DNA repair systems)

“RNA world” hypothesis

- first primitive “living” systems had RNA genome

Supported by multifunctional nature of present-day RNA

ribozymes - self-cleaving, self-slicing, self-elongation…

Pre-Darwinian evolution

Without self-replication, no entities to evolve through natural selection

Progressive Darwinian evolution

Strong selective advantage if able to propagate info & efficient production of useful proteins

Replication, transcription & translationmachinery “similar” in all life-forms

Period of rapid mutation, increased accuracy & efficiency of info transfer – gene organization & regulation

Origin of cellular life, communal web-of-life?

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

Doolittle & Brown PNAS 91:6721, 1994

Bittker Curr Opin Chem Biol 6:367, 2002

“Experimental evolution” in vitro

SELEX – iterated cycles of selection & amplification of sequences

PCR

RiNA GmbH

Test-tube evolution of ribozyme

- pool of ~1013 molecules- 140 nt (brown) randomly mutatedso “5% chance not wt sequence atany given position”

- after 9 rounds of selection & reproduction,4 “mutations” (pink sites) predominant

- selection for improved cleavageof DNA oligomer substrate

Freeman Fig. 16.5

“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.”Beaudry & Joyce Science 257:613, 1992

Papdopoulos, PNAS 96:3807, 1999

“Experimental evolution” in vivo

Comparison of positions of orthologous genes in Mycoplasma & Haemophilus

Fig.8.22