Lecture Outline 12/7/05 The human genome Most of our DNA is non-coding Various types of repetitive elements Gene families Some applications of genetic technologies Future of genomics? Course Review

On February 11, 2001, two groups published the sequence of the entire human genome

But that doesn’t mean we can read it . . .

Overview of the human genome Exons (regions of genes coding for protein, rRNA, tRNA) (1.5%) Repetitive DNA that includes transposable elements and related sequences (44%) Introns and regulatory sequences (24%) Unique noncoding DNA (15%) Repetitive DNA unrelated to transposable elements (about 15%) Alu elements (10%) Simple sequence DNA (3%) Large-segment duplications (5–6%)

Numbers and types of genes in different eukaryotes Most genes have uknown function

Areas of high and low gene density

Movement of eukaryotic transposable elements Transposon New copy of transposon is copied DNA of genome Insertion Mobile transposon (a) Transposon movement (“copy-and-paste” mechanism) Retrotransposon retrotransposon RNA Reverse transcriptase (b) Retrotransposon movement Figure 19.16

Many genes occur in gene families DNA RNA transcripts Non-transcribed spacer Transcription unit 18S 5.8S 28S rRNA (a) Part of the ribosomal RNA gene family Heme Hemoglobin -Globin -Globin -Globin gene family -Globin gene family Chromosome 16 Chromosome 11    2  1   G A    Embryo Fetus and adult Adult (b) The human -globin and -globin gene families  Many genes occur in gene families Ribosomal RNA genes Globin genes Figure 19.17

Histone gene distribution

Gene duplication due to unequal crossing over Nonsister chromatids Transposable element Gene Incorrect pairing of two homologues during meiosis Crossover and Figure 19.18 

Evolution of the human -globin and -globin gene families Ancestral globin gene      2 1   G A   -Globin gene family on chromosome 16  -Globin gene family on chromosome 11  Evolutionary time Duplication of ancestral gene Mutation in both copies Transposition to different chromosomes Further duplications and mutations Figure 19.19

Evolution of a new gene by exon shuffling EGF Epidermal growth factor gene with multiple EGF exons (green) F Fibronectin gene with multiple “finger” exons (orange) Exon shuffling duplication K Plasminogen gene with a “kringle” exon (blue) Portions of ancestral genes TPA gene as it exists today Figure 19.20 

Some other uses of genetic technology

Replacement of Neanderthals by Modern Humans Generations before present Currat and Excoffier 2004

Ovchinnikov et al 2000 Nature 404:490-493

Poaching Whales?

Data from Baker and Palumbi 1990 Minke whale Sample #19a Sample WS3 Sample #9 Sample #15 Sample #29 Sample #30 Sample #36 Sample #6 Sample #18 Sample #19b Humpback whale Gray whale Blue whale Sample #41 Sample #3 Sample #11 Sample WS4 Fin whale Sei whale Bryde’s whale Bowhead whale Right whale Pygmy right whale Sperm whale Pygmy sperm whale Sample #16 Harbor porpoise Sample #13 Sample #28 Hector’s dolphin Commerson’s dolphin Killer whale Data from Baker and Palumbi 1990 www.okstate.edu/artsci/zoology/ravdb/Cons.%20Genet...

Particularly variable regions of DNA can be used as “genetic fingerprints” Can any of these children be excluded from being the biological child of the father? Mother Father

The future? Patterns of expression? Regulatory networks? Gene-> phenotype Patterns of variation? What is all the non-coding DNA?

Patterns of Gene Expression “Gene Chips” or microarrays can compare expression levels of 1000s of genes at once

Understanding Variation