genetics 321 from mendel to genomes 10 weeks. jeff young, botanist [email protected] x3638 office:...
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Genetics 321From Mendel to Genomes
10 Weeks
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Jeff Young, [email protected]: BI412 Arabidopsis thaliana
Genome-based study of plant physiology and environmental
responses.Office Hours
M,W,F: 12:30 - 1:30 pm …by appointment.
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Class Business
• Bulletin Board outside of BI463,
– Answer Keys,– etc.
• Graded exams and quizzes,
– outside of BI412,
• Online Materials...
http://fire.biol.wwu.edu/young/321g07.html
...via Biology Department Home Page -> Courses -> Jeff Young’s Courses -> Genetics.
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Itinerary
• M W F, 10 - 11:20, 5 minute break (~10:45).
• M & F, Usually, questions and answers after break,
• W, (without exception) quiz 11:05 - 11:20,
• All midterms in class, 10:00 - 11:20,
– Final 10:30 - 12:30, Tuesday, December 11
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Genetics 321From Mendel to Genomes
10 Weeks
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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.
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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
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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.
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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.
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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
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Genetics ...the study of heredity and variation.
The most powerful tool in the biologists toolbox.
Not just for biologists,
- societal,
- personal.
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Classical Geneticseucaryotic
...the transmission of the primary hereditary material,
DNA Chromosomes
Genes
Genomes
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DNA Nucleotides“Bases”
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ChromosomesLong Polymers
Phosphodiester BondsBackbone
Hydrogen BondsDouble Helix
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Genomes
... 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
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Units of HeredityClassical Genetics
chromosome: DNA (Mb long) proteins
gene
DNA (kb long)
promoter: controls expression structural:
codes for a protein
Genome
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Transmission of Hereditary Materials (meiosis/sex)
...Meiosis: the process of two consecutive cell divisions in the diploid progenitors of sex cells.
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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.
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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.
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2n = 4Diploid(somatic cells)
Chromosome I Chromosome II
homologous chromosomes
homologous
chromosomes
Chromosome I Chromosome II
Haploid(sex cells)
n = 2
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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.
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AllelesAlternative forms of the same gene.
Alleles occur at the same locations (loci) on homologous chromosomes.
A- a-
B- b-
C- C-
Heterozygous
Homozygous
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Meiosis
S: synthesis of DNA, chromosomes are replicated.
Haploid Cell
Diploid Cell
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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
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M phase
Chromosome Structure(cartoons)
sister chromatids
sister chromatids
centromere: region of the chromosome where chromatids attach.
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Meiosis
S: synthesis of DNA, chromosomes are replicated.
M: meiosis ( two divisions) after one synthesis.
Haploid Cell
Diploid Cell
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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.
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Chiasmata
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Meiosis Prophase Icont.
Crossing Over: rearranges the genes from each parent.
A aA a
B B b b
a A
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Meiosis Metaphase I -- Telophase I
A aA a
B B b b
a A
AA
B B
a aa
b b
A
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Meiosis Prophase II -- Telophase II
aA
BB
Aa
bb
A A
B B b b
aa
no DNA synthesis
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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.
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Genetic Recombination I
Crossing over.
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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
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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
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Mendelian Genetics
• Gregor Mendel (1822-1884),
• Augustinian monk,
» Botanist,
• Pisum sativa,
• Garden pea,
» 1st “Model System”.
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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.
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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.
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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
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Nature 405, pp. 830Cell Cycle
~400 of 6022 Saccharomyces cerevisiae genes are active in conjunction with the cell cycle.
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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
? Mb
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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
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> 145 Gb (Aug, 2006) > 165,000 organisms
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Complete Genomic SequencesDNA Sequence:Reagent for the 21st Century
2001
9 ARCHAEAL
36 BACTERIAL
6 EUKARYAL
2007
• 345 Eukaryotic Genome Sequencing Projects
– Complete - 26, – Assembly - 130, – In Progress - 189
• 477 Complete Microbial Genomes
2007: ~ 1,793 Viral Genomes, >547 Organelles, others…
2007
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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...
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Post Genomics Era
Genetic Testing
Gene Therapy
Drug Discovery
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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
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Online Mendelian Inheritance In Man OMIM
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
Bioinformatics
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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
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"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."
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Friday
• Turn in take home quiz, beginning of class,
• Read Chapter 1, and review Chapter 3 if you are shaky with meiosis.