1 Problem: the DNA sequence alone does not directly inform us about - PDF document

Evolutionary Genomics The ultimate unit of heredity is the complete genome. Individual gene view of heredity Complete genome (E. coli) view of heredity 1

Problem: the DNA sequence alone does not directly inform us about phenotype We have much work to do: • genomes contain an immense amount of raw data • genomes are complex • we are required to use sophisticated numerical methods and powerful computers to analyze them Comparative Evolutionary Genomics Compare two or more genomes where common ancestor had same phenotype/functional properties: 1. DNA sequences encoding the proteins responsible for that phenotype/function will be conserved; i.e., present in both extant genomes. 2. Regulatory DNA sequences that control expression of genes that are regulated in the same ways will be conserved. 3. Sequences that encode or control structural genes that are responsible for differences between the organisms will have diverged. 2

The nature of the question determines the scale of the comparison. Unc-52 gene in human and worms Roundworms Human 3

Comparing eukaryotic genomes: friut fly- roundworm – yeast: > 1 billion years of evolution Percentage of genes (non-redundant) shared between genomes 40 35 30 25 20 15 10 5 0 Fly-Worm Worm-Fly Fly-Yeast Worm- Yeast Fly and worm share nearly twice as many genes. • The larger number appears to reflects greater number of signaling pathways and developmental pathways as comapred to yeast. • The big surprise is the similarity between fly and worm Rubin et al. 2000 Science 287:2204-2215. Human - chimpanzee: • 99% of gene content and order is conserved • 98-99% of genomes align at nucleotide level Human – mouse: • 90% of gene content and order is conserved • 40% of genomes align at nucleotide level (24% repetitive elements unique to humans; 33% unique in mouse) Above is rather crude example. By the end of this course you will comfortable reading papers on genomics that address much more sophisticated questions about evolution. 4

• rates of evolution from point mutation up to large scale genomic changes • nature of selection pressure / strength of selection pressure • identify new structural genes and regulatory genes • rate of recombination • rate of later gene transfer among genomes (prokaryotes) Fission verses fusion as a method of gene evolution within prokaryotic genes 5

Fission verses fusion as a method of gene evolution within prokaryotic genes Thermophillic species appear to have a higher rate of gene fission ? 6