1. 1 Is Gene Position Adaptively Favored?

2. 2 Why do we care? Genomic clusters of genes Yeast 98% of genes in metabolic pathways cluster (Lee & Sonnhammer) 25% of cell-cycle dependent genes are directly adjacent (Cho et al.) Drosophila 20% of genes in co-expression clusters (Spellman et al.)

3. 3 Why do we care? Genomic clusters of genes Arabidopsis 43% of genes in metabolic pathways cluster (Lee & Sonnhammer) Blocks of neighboring genes co-express (Williams & Bowles) Clusters up to 20 genes, 100kb Evolutionary process?

4. 4 Idea to test Gene clusters occur due to evolutionary processes Look for evidence of selection on clusters

5. 5 Method Plot co-expression vs recombination rate for each gene, compare to selection models Recombination rate Chromosomal position Co-expression / Co-expression

6. 6 Hill-Robertson Effect Reduction in the efficacy of selection In regions of low recombination, mutations are linked This limits the effective population size for region Mutations more likely to be fixed in small populations

7. 7 The test Selection: Relatively neutral - clusters scattered Positive - skew toward high recombination Negative - skew toward low recomb regions Recombination rate Chromosomal position Co-expression / Co-expression

8. 8 Method Plot co-expression vs recombination rate for each gene, compare to selection models Recombination rate Chromosomal position

9. 9 Recombination rate Estimated for 17.8k genes by Jianhua Hu cM (genetic dist) Chromosome position

10. 10 Recombination rate

11. 11 Method Plot co-expression vs recombination rate for each gene, compare to selection models Chromosomal position Co-expression / Co-expression

12. 12 Expression Data NASC Expression data Affymetrix arrays of Arabidopsis genes ~22,700 genes 59 datasets, 534 arrays AtGenExpress data >500 datasets, 1300 arrays

13. 13 Co-expression measurement Measures of co-expression R – Pearson / Spearman correlation Linear relationship between points (scaled) Demonstrate positive or negative correlation (-1..1) Euclidean distance Distance between two points Demonstrates correlation (0..1) Calculate for neighboring genes

14. 14 Other factors Factors to consider: Tandem duplicates – likely to co-express Array conditions

15. 15 Method Plot co-expression vs recombination rate for each gene, compare to selection models Recombination rate Chromosomal position Co-expression / Co-expression

16. 16 Regional transcription Mechanisms Matrix attachment sites Change chromatin loops (3D structure) Insulators, Boundary elements

17. 17