Development: differentiating cells to become an organism

Cells function differently because they express different genes.

The proper control of gene expression is critical for proper development.

Irreversible packaging of DNA partially explains the loss of totipotency. Often in the form of DNA methylation

Embryonic Stem Cells are totipotent Adult Stem Cells are pluripotent (only form some cell types) Fig 19.14

Use of stem cells shows promise to cure various diseases by replacing damaged cells

Use of embryonic stem cells has generated controversy… Why?

What is life? When does it begin?

Fertilization and mitosis without implantation is common

Use of embryonic stem cells has generated controversy… Why?

What genetic mechanisms regulate/allow development?

Why change gene expression? Different cells need different components Responding to the environment Replacement of damaged/worn-out parts How does a cell know what genes to express?

Flower parts: Complexity from a few simple genes 4 whorls of a flower Fig 23.23

Each whorl expresses a specific combination of three genes Fig 23.24

How does a cell know where it is? Fig 23.2

Drosophila Development Fig 23.4

Polarity development by mRNA localization Fig 23.5

Hox genes regulate the identity of body parts Fig 23.11

Expression of hox genes in the embryo give rise to different adult body parts. embryo adult Fig 23.11

Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor) Fig 23.16

Many hox proteins have common sequences (these are from Drosophila) Fig 23.13

helix-turn-helix: a common DNA-binding motif Fig 23.13

Many developmental genes are transcription factors these are from Drosophila

“Introduction to Genetic Analysis” 9 th ed. ©2008 by Griffiths et al Fig Interaction of genes can set gradients in cells/organisms that signal how different regions should develop.

Reporter gene: protein coding region promoter reporter gene (luciferase, etc) easily visualized protein promoter “Introduction to Genetic Analysis” 9 th ed. ©2008 by Griffiths et al Fig 12.19

Interaction of genes can set gradients in cells/organisms that signal how different regions should develop. “Introduction to Genetic Analysis” 9 th ed. ©2008 by Griffiths et al Fig 12.18

Expression of hox genes in the embryo give rise to different adult body parts. embryo adult Fig 23.11

The order of Hox genes parallels the order of body parts in which they are expressed Fig 23.17

25,00012 How are genomes organized? Tbl 20.2

deogr[Xpter:Xqter],genes[1.00: ] Map of human chromosome 20 How does the organization of a genome affect its function?

Figure Molecular Biology of the Cell, 4th ed by Alberts et al (Adapted from S. Baxendale et al., Nat. Genet. 10:67–76, 1995.) Comparison of Fugu and human huntingtin gene: 7.5 X bigger both have 67 exons, connected by lines (green indicates transposons prevalent in human version) (puffer fish)

Some genes have several similar sequences within the genome: known as a gene family Fig 8.7

Hemoglobin (carries O 2 in the blood) is comprised of a gene family in humans Fig 8.7

Different members of the hemoglobin gene family are expressed at different developmental stages

Fetal Hb binds O 2 more strongly than maternal Hb

Pseudogenes have the structure of a gene, but are not expressed.

Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E. Mills et al. The American Journal of Human Genetics 78: and Which transposable elements are active in the human genome? (2007) Ryan E. Mills et al. Trends in Genetics 23:

Transposons: mobile DNA

Transposons comprise much of human DNA

Fig 17.12C Retro-transposons move via an RNA intermediate

Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E. Mills et al. The American Journal of Human Genetics 78:

Humans and chimpanzees shared a common ancestor about 6 million years ago

human chimp Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E. Mills et al. The American Journal of Human Genetics 78: Humans have more transposons than chimps

Conclusions: Transposons may play a role in evolution More abundant transposons in humans show “recent” transposon activity

Conclusions: Transposons may play a role in evolution More abundant transposons in humans show “recent” transposon activity What affect do transposons have in humans?

Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E. Mills et al. The American Journal of Human Genetics 78:

Tbl 1 Which transposable elements are active in the human genome? (2007) Ryan E. Mills et al. Trends in Genetics 23: Does transposition cause disease?

An active copy of the L1 transposon ‘jumped’ into the factor VIII gene and caused hemophilia

Diseases caused by transposon insertion: Duchenne muscular dystrophy Coffin-Lowry syndrome Fukuyama-type congenital muscular dystrophy (FCMD) colon cancer chronic granulomatous disease X-linked dilated cardiomyopathy familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism neurofibromatosis type 1

Active human transposons have been estimated to generate about one new insertion per 10–100 live births Which transposons are mobile?

Tbl 1 Which transposable elements are active in the human genome? (2007) Ryan E. Mills et al. Trends in Genetics 23: Which transposons are mobile?

Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans. For example, over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans.

Conclusions: Transposons may play a role in evolution More abundant transposons in humans show “recent” transposon activity Transposons are still active, and can cause mutations and disease.

Millions of Hectares Texas = 70 ha Next… Biotech Global area planted with GM crops