Gene & Genome Evolution 1

Gene & Genome EvolutionChapter 9

You will not be responsible for:

Read the How We Know section on Counting Genes, and be able to discuss methodologies for doing so.

Questions in this chapter you should be able to answer:Chapter 9- #1 -7 , 9, 10 - 16, 18

Gene & Genome Evolution 2

How do genes evolve over time?

Mutation of coding regions

Mutation of regulatory regions

Chromosome/Gene/Exon duplications

Exon/intron shuffling & Transposition

Horizontal gene transfer

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Exon duplication & shuffling is common

Gene & domain duplications occurred during evolution of the “Ig-Superfamily”

Exon shuffling &duplication has occurred duringevolution of these genes

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Gene duplications are common

Divergence of function

e.g. Fetal/human hemoglobin

Families of related genes

Pseudogenes can result

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Horizontal Gene Transfer-- can move blocks of genes

Asexual transfer of genes between organisms

Most common in single-celled organisms-- why?

Bacterial genetic recombination-- spread of Ab resistance

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Simple mutations to regulatory genes can cause dramatic changes in development

Explains “Punctuated Equilibrium”

Mutations to “master regulatory gene”

Antennapedia (antp)-- antennae transformed to legs

bithorax (bx) + postbithorax (pbx)-- extra set of wings

Chromatin Structure and Replication 7

Trends in genome evolution

1) Accumulation of non-coding DNA

2) Accumulation of transposable elements

3) Loss of GC pairs

4) Intron Expansion

5) Accumulation of SNPs

Figures 9-32 & 9-33

Chromatin Structure and Replication 8

2) Accumulation Transposable elements

Alu – about 300 Bp-- 106 copies-- new Alu insert ~1/200 live births

L1 (Line) elements-- longer-- encode genes

reverse transcriptase& endonuclease

-- 5 x 105 copies

Many copies are “dead”

Can be disruptive-- cancers

Chromatin Structure and Replication 9

How do transposable elements move?

DNA-only mehanism-- common in bacteria, plants, yeast, insects

Inverted sequences

Mechanism of cut and paste transposition

Chromatin Structure and Replication 10

Alu and Li are retrotransposons

Pass through RNA form

Use reverse transcriptase

Transposable elements can move genes and exons

e.g., Antibiotic resistance genes

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3) Loss of GC pairs Vertebrates

‘Cytosine methylation and gene regulation

CpG’ vs ‘GC’ bp

Methylation of CpG leads to loss of GC bp’s

Deamination of methyl-C yields T – G mismatch

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Creation of CpG islands

CpG remains in ‘islands’

Where found?housekeeping genesnon-coding regions

FrequenciesGroup GC CpG Fish & amphibians 44% 1.8%Birds and mammals 42% 1.13% “GC-islands” 4-6% Jabbari, et al. 1997 Gene 205:109-118

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4) Intron expansion

Genome sizesPuffer fish: 4 x 108

Human: 3 x 109

Huntingtin gene sizePuffer fish: 2.4 x 104

Human: 1.8 x 105

All 67 exons align!!

Expansion and mobile elements occur in introns

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5) Accumulation of single-nucleotide polymorphisms (SNP)

distinguish individual genomes

Consequence of “point mutations”

107+ documented in humans

Can influence:Our individual physical traitsDisease susceptibilityRisk factors for disorders

e.g., Macular DegenerationSNP in Complement factor HHis Tyr5 – 7x >risk

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What is a “silent mutation”?

Why are they not always silent?

Sometimes: Wobble positionNon-coding regions

Sometimes not:regulatory sites chromosome codon usage

Arginine tRNA occurrence

Codon tRNA [tRNA]1

CGU arg2 5.54CGC arg2 CGG arg3 1.45AGA arg4 2.64AGG arg5 1.611tRNA abundance in E. coli: Burg & Kurland (1997) J. Mol. Biol. 270: 5442Frequency in E. coli O127:H6 http://www.kazusa.or.jp/codon/

What would be the expected effect on translation rate of … … CGU CGC mutation? … CGU CGG mutation?