Genetics 321From Mendel to Genomes

10 Weeks

Jeff Young, Botanistemail: via contact form on web site

x3638Office: BI412 Arabidopsis thaliana

Genome-based study of plant physiology and environmental

responses.Office Hours

MW: 1:00- 2:00 pm, F: 10 - 11 …by appointment.

Class Business

• Bulletin Board outside of BI463,

– Answer Keys,– etc.

• Online Materials...

http://biol.wwu.edu/young/321

...via Biology Department Home Page -> Courses -> Jeff Young’s Courses -> Genetics.

Itinerary

• M W F, 11:30 - 12:50, 5 minute break (~12:15).

• M & F, Usually, questions and answers after break,

• W, (without exception) quiz 12:35 - 12:50,

• All midterms in class, 12:35 - 12:50,

– Final: Friday, December 11, 10:30 pm - 12:30 pm

Essential Genetics: A Genomics Perspective by Hartl and Jones, 4th ed.

ISBN: 0-7637-3527-2

Text Assignments:

• Unless amended in class, all reading assignments listed on the syllabus are required, • Additional reading assignments will be made,

• You will be responsible for ‘in class’ additions and changes made to the syllabus.

Three hourly exams plus final exam (450 pts),

You will have the full session time to complete each exam,

You will be allowed one 11” x 8.5” crib sheet, one side, for each exam,

Exams - 150 points each, Final Exam cumulative.

Quizzes will be given every Wednesday (total 100 pts),

will cover the basics of the assigned reading (including that day's assignment),

quizzes 12.5 points each, ~15 minutes,

quizzes may be taken in teams of two (except Q #1 and #2),

No Make-up Quizzes, absolutely no exceptions,No Make-up Quizzes, absolutely no exceptions,

can drop two (2) lowest quiz scores (except Q #1 and #2).

Total course points - 550

Grades

Extra Credit

• e-mail me a synopsis of a news story concerning Genetics, in the body of the email, 1 per email,

• 1 point each for up to 15 points,– maximum, 2 per week,

• journal, date, byline, who, where, what and the significance,

• in English sentences,

– not an automatic point, – must be well presented.

Extra Credit Sources• paper newspapers,

• online newspapers,

– do not just cut and paste,

– I reserve the right to be the final judge and arbiter of valid extra credit contributions,

• you will receive automatic notification(within 24 hours) that your email got to me. This is not automatic approval.

• if I suspect that liberties are being taken, your extra credit account will be tallied to zero permanently,

• I’ll let you know if I have a problem with your entry.

• no professional journals.

Genetics 321From Mendel to Genomes

10 Weeks

Gen

omic

ston

UnhappyhamYou are here...

Skip Class

Don’t read material

Don’t work problems

Nature Lake MapGeneticsville

Rt 321

Hard Mountains

Get behind

Young Pass

Don’t Listen

Genetics ...the study of heredity and variation.

The most powerful tool in the biologist’s toolbox.

Not just for biologists,

- societal,

- personal.

Classical Geneticseucaryotic

...the transmission of the primary hereditary material,

DNA Chromosomes

Genes

Genomes

DNA Nucleotides“Bases”

ChromosomesLong Polymers

Phosphodiester BondsBackbone

Hydrogen BondsDouble Helix

Genome

... haploid chromosome component of an organism,

•human (23), 3 Gb,• fruit fly (4), 120 Mb,• nematode (5), 100 Mb,• mustard (5), 120 Mb,• yeast (16), 12 Mb,• bacteria, (1), ~5-15 Mb.

chromosome

~ 5 - 150 Mb long

OrganizationUnits of Heredity

gene

DNA (kb)

promoter: controls expression structural:

codes for a protein

chromosome: DNA (Mb) proteins

GenomeDNA (Mb - Gb) proteins

Transmission of Hereditary Materials (meiosis/sex)

...Meiosis: the process of two consecutive cell divisions in the diploid progenitors of sex cells.

Meiosis

Cell Biology

...the mechanism, timing and steps of cell division,

…how a cell divides,

…growth and repair.

Genetics

…a major result of cell division is the partitioning of DNA,

…transmission of genomes,

…via the transmission of chromosomes.

Chromosomes…self-replicating genetic structures.

• two copies of each chromosome are present at some stage of an eukaryotic

organism’s life cycle,

– haploid: cells carrying one full set of chromosomes,

– diploid: cells carrying two full sets of chromosomes,

• n = number of haploid chromosomes.

• 2n = number of chromosomes in a diploid organism.

2n = 4Diploid(somatic cells)

Chromosome I Chromosome II

homologous chromosomes

homologous

chromosomes

Chromosome I Chromosome II

Haploid(sex cells)

n = 2

Homologous Chromosomes

…a pair of chromosomes containing the same linear gene sequence,

each derived from one parent,

– homologous chromosomes carry the same complement of genes,

– the DNA sequence of the genes on homologous chromosomes may differ,

• alleles: genes at the same location (locus) on homologous

chromosomes, but that have different DNA sequences.

AllelesAlternative forms of the same gene.

Alleles occur at the same locations (loci) on homologous chromosomes.

A- a-

B- b-

C- C-

Heterozygous

Homozygous

Meiosis

S: synthesis of DNA, chromosomes are replicated.

Haploid Cell

Diploid Cell

Homologous Chromosomes

Synthesis

A- a-

B- b-

-A -a

-b-Brepresents gene A,from one parent. represents the

same gene from the other parent, codes for the ~same protein, may have a slightly different DNA sequence.Homologous Chromosomes

M phase

…after replication.

Chromosome Structure(cartoons)

sister chromatids

sister chromatids

centromere: region of the chromosome where chromatids attach.

Meiosis

S: synthesis of DNA, chromosomes are replicated.

M: meiosis ( two divisions) after one synthesis.

Haploid Cell

Diploid Cell

Meiosis Prophase I

… Synapsis: the highly specific parallel alignment of homologous chomosomes during the first division of meiosis,

A A a a

B B b b

…tetrad: the two homologous chromosomes become attached along their length in a structure termed a tetrad.

Chiasmata

Meiosis Prophase Icont.

Crossing Over: rearranges the genes from each parent.

A aA a

B B b b

a A

Meiosis Metaphase I -- Telophase I

A aA a

B B b b

a A

AA

B B

a aa

b b

A

Meiosis Prophase II -- Telophase II

aA

BB

Aa

bb

A A

B B b b

aa

no DNA synthesis

Meiosis is critical for sexual reproduction in all diploid

organisms

...meiosis leads to the formation of gametes,

– gametes (one from each parent) conjugate to form a zygote,

...meiosis is the basis for extensive variation among members of a population.

Genetic Recombination I

Crossing over.

I-A II-b I-AII-B II-B

I-aI-aII-b

I-A I-a II-b II-B 2n combinations of chromosomes,

n = haploid number of chromosomes.

Random Assortment of Chromosomes.

Genetic Recombination II

2n combinations of chromosomes n = number of chromosomes

• n = 1, 2n = 2• n = 2, 2n = 4• n = 3, 2n = 8• n = 5, 2n = 32 Arabidopsis• • • n = 23, 2n = 8,388,608 H. sapiens• n = 39, 2n = yip! dog

Mendelian Genetics

• Gregor Mendel (1822-1884),

• Augustinian monk,

» Botanist,

• Pisum sativa,

• Garden pea,

» 1st “Model System”.

Model Systems

• Modern Biology depends largely on the ability to study simple organisms, and then apply the resulting principles to more complex systems,

– i.e., ask simple questions about immensely complex processes,

– the answers are often simple, though not obvious.

Model Organisms

• Ease of cultivation,

• Rapid Reproduction,

• Small size,

• Fecund (large brood size),

• Mutants are available and easy to identify,

• Broad literature and experimental background available.

Model Organisms

P. sativum pea 7 ~26,0,000

organism aka n # genes

E. coli bacteria NA 4,377S. cereviisae yeast 16C. elegans roundworm 5 19,000Drosophila fruit fly 4 13 379Arabidopsis dicot plant 5 25,498M. musculus mouse 40 100,000

H. sapiens human 23 100,000 25,000-40,000?

25,000- 40,000?

20,000- 25,000?

5,770

General Cell Function

ECOCYC

Nature 405, pp. 830Cell Cycle

~400 of 6022 Saccharomyces cerevisiae genes are active in conjunction with the cell cycle.

Model Organisms

P. sativum pea 7

organism aka n

E. coli bacteria NAS. cereviisae yeast 16C. elegans roundworm 5Drosophila fruit fly 4Arabidopsis dicot plant 5M. musculus mouse 40

H. sapiens human 23

# DNA bases

4,639,675

12,495,682100 Mb100 Mb120 Mb120 Mb

3 Gb

Genome Sizes

5 Gb

Vukmirovic and Tilghman, Nature 405, 820-822 (2000)

“Biology is in the midst of an intellectual and experimental sea change....

...essentially the discipline is moving from being largely a data-poor science to becoming a data-rich science. ”

GenomicsDNA: Reagent for the 21st Century

> 206 Gb (Dec. 2007) > 165,000 organisms

Presently

Reference, GOLD

Genomics

• The systematic study of genomes that begins with large scale DNA sequencing (Structural Genomics),

– Functional genomics: how particular DNA sequences facilitate biological functions,

– Comparative Genomics: differences between individuals, differences between species, etc.

– Bioinformatics: computational discipline that has evolved to handle modern biological data...

Post Genomics Era

Genetic Testing

Prostate Cancer, KLF6

Hypertension, WNK Kinases

Breast Cancer, BCR-ABL

Alzheimer’s, linked to Chr. 10

…lots of others.

Drug Discovery

Anti-Plasmodium (malaria)

Gene Therapy

Blindness: Leber congenital amaurosis

Parkinson’s: GABA receptor

Skin Cancer: T-Cell lymphocytes

More Genomics

Fundamental Research-Baxter, IR, Young, JC, Armstrong, G, Fosters, N, Bogenschutz, N, Cordova, T, Peer, WA, Hazen, SP, Murphy, A, Harper, JF. (2005) A plasma membrane H+-ATPase is required for the formation of proanthocyanidins in the seed coat endothelium of Arabidopsis thaliana. PNAS, 102 (7): 2649–2654

- Robertson WR, Clark K, Young JC, Sussman MR. (2004) An Arabidopsis thaliana Plasma Membrane Proton Pump Is Essential for Pollen Development. Genetics. 168(3):1677-87

Bt Toxin Resistance

Metagenomics

Dietary studies of scat.

Environmental/ Ecological

Online Mendelian Inheritance In Man OMIM

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

Bioinformatics

Post-Genomics Biology

“The new paradigm, now emerging, is that all genes will be known (in the sense of being resident in databases available electronically), and that the starting point of a biological investigation will be theoretical.”

- Walter Gilbert Nobel Laureate, Chemistry DNA Science

"I guess there's cool stuff about science," Watanabe continued, "like space travel and bombs. But that stuff is so hard, it's honestly not even worth the

effort."

Friday

• Turn in take home quiz, beginning of class,

• Read Chapter 1, and review Chapter 3 if you are at all shaky with meiosis.