Gene & Genome Evolution1 Chapter 9 You will not be responsible for: Read the How We Know section on Counting Genes, and be able to discuss methodologies.

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Gene & Genome Evolution1 Chapter 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, , 18

Gene & Genome Evolution2 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

Gene & Genome Evolution3 Exon duplication & shuffling is common Gene & domain duplications occurred during evolution of the “Ig-Superfamily” Exon shuffling & duplication has occurred during evolution of these genes

Gene & Genome Evolution4 Gene duplications are common Divergence of function e.g. Fetal/human hemoglobin Families of related genes Pseudogenes can result

Gene & Genome Evolution5 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

Gene & Genome Evolution6 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 Replication7 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 Replication8 2) Accumulation Transposable elements Alu – about 300 Bp copies -- new Alu insert ~1/200 live births L1 (Line) elements -- longer -- encode genes reverse transcriptase & endonuclease -- 5 x 10 5 copies Many copies are “dead” Can be disruptive -- cancers

Chromatin Structure and Replication9 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 Replication10 Alu and Li are retrotransposons Pass through RNA form Use reverse transcriptase Transposable elements can move genes and exons e.g., Antibiotic resistance genes

Gene & Genome Evolution11 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

Gene & Genome Evolution12 Creation of CpG islands CpG remains in ‘islands’ Where found? housekeeping genes non-coding regions Frequencies GroupGC CpG Fish & amphibians 44% 1.8% Birds and mammals 42% 1.13% “GC-islands” 4-6% Jabbari, et al Gene 205:

Gene & Genome Evolution13 4) Intron expansion Genome sizes Puffer fish: 4 x 10 8 Human: 3 x 10 9 Huntingtin gene size Puffer fish: 2.4 x 10 4 Human: 1.8 x 10 5 All 67 exons align!! Expansion and mobile elements occur in introns

Gene & Genome Evolution14 5) Accumulation of single-nucleotide polymorphisms (SNP) distinguish individual genomes Consequence of “point mutations” documented in humans Can influence: Our individual physical traits Disease susceptibility Risk factors for disorders e.g., Macular Degeneration SNP in Complement factor H His  Tyr 5 – 7x >risk

Gene & Genome Evolution15 What is a “silent mutation”? Why are they not always silent? Sometimes: Wobble position Non-coding regions Sometimes not: regulatory sites chromosome codon usage Arginine tRNA occurrence Codon tRNA [tRNA] 1 CGU arg CGC arg2 CGG arg AGA arg AGG arg tRNA abundance in E. coli: Burg & Kurland (1997) J. Mol. Biol. 270: Frequency in E. coli O127:H6 What would be the expected effect on translation rate of … … CGU  CGC mutation? … CGU  CGG mutation?