Ch 12: Genomes

Open Reading Frame

Transcription Termination Sequence PROMOTER (TATA box) A B C Transcription Termination Sequence DNA A Exon B Intron C Pre-mRNA Mature RNA 5’ Cap Start Codon A C Stop Codon Poly-A Tail Open Reading Frame

Human Genome

Human Genome Project 1970: (Frederick Sanger)- 13 years, $2.7 billion 2000: (PCR/Flourescent Tagging)- days, $thousands CHALLENGE: “Reads” or fragments of DNA are so hard to put in order 2.5M fragments in 100bp Introduced the field of Bioinformatics

Bioinformatics

Bioinformatics: Genomics Functional Genomics look at Open Reading Frame: Recognize the START/STOP of a gene Where introns are removed Comparative Genomics- compare genomes of other organisms

Bioinformatic Studies Genomics Proteonomics Metabolomics Determine DNA nucleotide order & genes made from it PCR amplifies DNA fragments (reads), & Fluorescent tags are added Determine all possible expressed proteins Gel Electrophoresis Mass Spectroscopy Determine metabolites (enzyme reactions) Hormones, signal molecules, antibiotics Spectroscopy gives “chemical snap shots”

GENOME PROTEOME METABOLOME PHENOTYPE E E I E E Gene mRNA Protein Metabolites *1 gene has many exon combo’s, therefore, many protein possibilities *different in different environments Genome

Genome Differences

Genome Differences Prokaryotic Genome Eukaryotic Genome Large Small (160,000-12,000,000bp) circular chromosome Mostly protein-coding DNA (minimal introns) Tiny Plasmid DNA passes between individuals Transposons- small movable sequences of DNA that can bounce around Large More Protein-Coding DNA Lots of Regulatory Sequences (Transcription Factors) Mostly Non-Coding DNA

Findings from the Genome

Helpful Organisms Functions of the Eukaryotic Genome Yeast (Saccharomyces cerevisiae)- organelles Fruit Fly (Drosophila melanogaster)- genetics Roundworm (Caenorhabditis elgans)- embryonic differentiation Functions of the Eukaryotic Genome

Gene Families (closely related genes) Gain Functions 1 functional gene/protein, while the other genes mutate *Evolution Ex. Hemoglobin (ɑ-globin, ß-globin, ϒ-globen) ADULT: ɑ, ɑ, ß, ß FETUS: ϒ *holds more oxygen –gets oxygen from mom BEFORE BIRTH: ɑ, ɑ, ß, ß Pseudogenes (Ψ)- a protein that lost its function due a mutation

Repetitive Sequences Don’t code for proteins Highly Repetitive (<100bp)- repeat 1,000x 10% of human genome (50% in fruit flies) Short Tandem Repeats (STR’s) (1-5bp)- repeat 100x Moderately Repetitive (Transposons) -repeat 10-1,000x 40% human genome Retrotransposons- RNA copies of themselves that get turned back into DNA DNA Transposons- stay DNA, just move around

Genome Surprises Splicing (RNA editing) causes way less protein-coding genes than expected Gene sizes can vary Genes: 1,000-2,400,000bp Protein Size: 100-5,000 amino acids All human genes have introns A lot of the genome is non-coding, but functional 50% of the Genome is Transposons & Repetitive Sequences Genome is 97% identical in humans

Benefits Identify Genetic Disorders with Halotype Maps Halotype- piece of chromosome with a set of SNP’s Use Single Nucleotide Polymorphism (SNP’s)- point mutations, passed down in groups DNA Fingerprinting- Easily display Short Tandem Repeats (STR’s) FBI stores 13 STR loci in its database Pharmacogenomics- how people’s genetics would react to a drug Proteomics- compare proteins to find out evolutionary relatives Metabolomics- relate metabolites to diseases (diabetes)