1. EVOLUTIONARY AND COMPUTATIONAL GENOMICS Shin-Han Shiu Plant Biology / CMB / EEBB / Genetics / QBMI

2. Duplicate genes in the genome  Arabidopsis gene families* *: Clusters of Markov clustering using all-against-all BLAST E values as distance measures

3. Focus I: Duplication Mechanism and Loss Rate Gene Duplications MechanismsConsequences Preferential retention

4. Gain vs. Loss  3 rounds of whole-genome duplications in the Arabidopsis lineage 15,000* 30,000 60,000 120,000 Arabidopsis gene content: 21,000** *: Number of orthologous groups in shared families between Arabidopsis and rice. **: Number of genes in shared families. Genome duplications + tandem duplications – gene losses =

5. Receptor Kinase Shiu & Bleecker 2001. Science’s STKE

6. RLK family sizes in 16 eukaryotes Organism Number of genes Kinase superfamily RLK/Pelle family Size Percent total gene Percent total kin Arabidopsis thaliana25,81410416152.38259.1 Oryza sativa subsp. indica~35,000160711313.23170.4 Chlamydomonas reinhardtii~12,20041420.0160.5 Plasmodium falciparum5,3349410.0191.1 Plasmodium yoelii7,6817010.0131.4 Caenorhabditis elegans19,48441710.0050.2 Drosophila melanogaster13,80826210.0070.4 Anopheles gambiae15,08821610.0070.5 Ciona intestinalis15,85231660.0381.9 Fugu rubripes33,60963260.0180.9 Mus musculus22,44449530.0130.6 Homo sapiens22,98047240.0170.8 Saccharomyces cerevisiae64491130-- Candida albicans6,164950-- Neurospora crassa100821040-- Schizosaccharomyces pombe49451090--

7. Intro 1: Duplicate genes in the genome *: Clusters of Markov clustering using all-against-all BLAST E values as distance measures Protein kinase: ~1000 Hanada & Shiu, in prep.

8. Focus II: Differential Retention of Duplicates Gene Duplications MechanismsConsequences Preferential retention

9. Genome Remodeling in Polyploids  Genome duplication occur frequently in plants  What is the fate of duplicates?  Mostly lost  But how fast did gene losses occur

10. What is tiling array  Does not rely on annotation Exon UTR Intron Cis-regulatory elements Novel genes MAR (Matrix attachment regions) Transcript array Tiling array

11. Differences in Duplicability CategoryArabidopsisHuman Defense response Proteolysis Transport Ion channel activity Metabolism Development Protein kinase activity Transcription factor activity  Duplicability  The propensity for the retention of a duplicate gene  Computational analysis of genome-wide trend

12. Gene family expansion and stress responsiveness  Exp: recently expanded genes T: tandem, N: non-tandem

13. Focus III: Functional Consequences Gene Duplications MechanismsConsequences Preferential retention

14. Functional Consequences of Duplication  Functional divergence and conservation  Is it because of changes in cis-regulatory elements or coding sequences  How are duplicates retained, subfunctionalization or neofunctionalization

15. Stress cis-regulatory logic  Develop bioinformatics pipelines for cis-element prediction and inference of stress expression patterns Clusters of genes with similar expression profiles Machine learning Motif functional prediction Cis-regulatory logic Expression data Over-represented sequence motifs in 5’ regions Experimental validations

16. Detailed Functional Studies of Duplicate Genes  Functional analyses of DDF1 and DDF2 transcription factors  Derived from recent whole genome duplication in Arabidopsis  Related to the well known CBF factors involved in cold and draught stress DDFs Promoter GFP Knockouts Over- expression studies Interacting proteins Binding targets DDFs Promoter GFP Knockouts Over- expression studies Interacting proteins Binding targets Arabidopsis thalianaArabidopsis lyrata

17. Recent completion …