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 genomeExons (regions of genes codingfor protein, rRNA, tRNA) (1.5%)

RepetitiveDNA thatincludestransposableelementsand relatedsequences(44%)

Introns andregulatorysequences(24%)

UniquenoncodingDNA (15%) Repetitive

DNAunrelated totransposableelements(about 15%)

Alu elements(10%)

Simple sequenceDNA (3%)

Large-segmentduplications (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

TransposonNew copy oftransposon

Transposonis copied

DNA of genome

Insertion

Mobile transposon

(a) Transposon movement (“copy-and-paste” mechanism)

RetrotransposonNew copy of

retrotransposon

DNA of genome

RNA

Reversetranscriptase

(b) Retrotransposon movement

Insertion

Figure 19.16

 Many genes occur in gene families

DNA RNA transcripts

Non-transcribedspacer Transcription unit

DNA18S 5.8S 28S

rRNA

5.8S

(a) Part of the ribosomal RNA gene family

28S

18S

Heme

Hemoglobin

-Globin

-Globin

-Globin gene family -Globin gene family

Chromosome 16 Chromosome 11

2 1

2 1 G A

EmbryoFetus

and adult Embryo Fetus Adult

(b) The human -globin and -globin gene families

Figure 19.17

Ribosomal RNA genes

Globin genes

Histone gene distribution

Gene duplication due to unequal crossing over

Nonsisterchromatids

Transposableelement

Gene

Incorrect pairingof two homologuesduring meiosis

Crossover

and

Figure 19.18 

 Evolution of the human -globin and -globin gene families

Ancestral globin gene

21

2 1 G A

-Globin gene familyon chromosome 16

-Globin gene familyon chromosome 11

Evo

lutio

nary

tim

e

Duplication ofancestral gene

Mutation inboth copies

Transposition todifferent chromosomes

Further duplicationsand mutations

Figure 19.19

Evolution of a new gene by exon shuffling

EGF EGF EGF EGF

Epidermal growthfactor gene with multipleEGF exons (green)

F F F F

Fibronectin gene with multiple“finger” exons (orange)

Exonshuffling

Exonduplication

Exonshuffling

K

F EGF K 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 presentCurrat and Excoffier 2004

Ovchinnikov et al 2000 Nature 404:490-493

Poaching Whales?

Minke whale

Minke whale

Sample #19a

Sample WS3

Sample #9

Sample #15

Sample #29

Sample #30

Sample #36

Sample #6

Minke whale

Sample #18

Sample #19b

Humpback whale

Humpback whale

Gray whale

Gray whale

Blue whale

Blue whale

Sample #41

Sample #3

Sample #11

Sample WS4

Fin whale

Fin whale

Sei whale

Sei whale

Bryde’s whale

Bowhead 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

www.okstate.edu/artsci/zoology/ravdb/Cons.%20Genet...

Data from Baker and Palumbi 1990

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