Notes from "The Gene: History of an Idea" with Donald Morisato
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Carl Woese 1960s
Sequence of rRNA
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Fitness Tradeoff
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Germline - gametes
Soma - all other tissues
Haploid - n (copy of set of chromosomes; copy of each type of chromosome)
Humans, n=23
Diploid - 2n
Humans, 2n=46
Homolog- (Homologous Chromosome)
Paternal + meternal copy of specific chromosomes
Allele- different forms of a particular gene
Genotype - specific alleles for a gene or genes
Phenotype - observable manifestation of a genotype, depends on environment
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"Modern synthesis"
1) Hereditary variations
2) Genes mutate - new alleles
3) Populational Process - allele frequencies
4) Natural selection can alter populations beyond the original range of variation by increasing the frequency of alleles that give rise to new phenotypes.
5) Speciation is the origin of 2 or more species from a single common ancestor.
Unifyring Ideas in Modern Biology
> Theory of Evolution
> Cell Theory
> Chromosome Theory of Inheritance
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Stages of Human Development
* Gametogenesis
* Fertilization > Fertilized egg/zygote
* Cleavage
* Blastula > Gastrulation
* Gastrula
* Organogenesis
* Trimesters
* Newborn
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Chromosome > Telomere / Centromere
Chromosomes are linear fragments of DNA
Replication
Centrosome (Microtubule organizing center)
Spindle Fiber (Microtubules - polymers of tubulia)
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DNA is highly negatively charged, histone proteins are negatively charged
* Each Chromatid is a single DNA molecule
* Within a nucleus, DNA is normally tightly packaged with histone to form chromatin.
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Mitosis > Soma / somatic tissue
Meisosis > Germline
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Mitosis: cell division is highly regulated
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Cell cycle
G2 > Cell volume increases chromatid > sister chromatids as cell prepares to divide. Two nuclei come from one, before cell finally divides.
Cytokinesis
G0
G1
G2
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"A" is an allele of a gene on this chromosome
Homologs
A, a = alleles of "A" gene
B, b = alleles of "B" gene
Nucleus interphase
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Genotype
Aa Bb
A/a ; B/b
DNA Replication (S-phse)
Sister chromatids
Mitosis is conservative
One parental cell or "mother cell" > two daughter cells
Prophase
Metaphasic plate
Anaphase / Telophase
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Meiosis
S-phase
Sister chromatids do not come apart
Homologous pair (Synapsis)
Crossing over occurs
Metaphasic plane
Prophase 1 = Meiosis 1
Metaphase 1 = Meiosis 1
First division
Segregation as pair
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Transcription (RNA synthesis) requires RNA polymers
Gene "Read" "Expressed" "Transcribed"
RNA-like strand / nontemplate strand / coding strand
template strand
Stages of Transcription
- Initiation < Major point of regulation
- Elongation
- Termination
Promoter, transcription, coding sequence
Open Reading Frame (ORF)
Coding region
Non-coding region (non-coding regulatory sequences)
Involved in controlling transcription
Promoter - short DNA sequence that binds RNA polymerase enabling transcription to begin
Terminator - short DNA sequence that releases RNA polymerase from template DNA
Enhancers - DNA sequences (only in eukaryotic genes) that act as binding sites for regulatory transcription factors.
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Bacteria - "Naked" DNA, phosphate backbone exposed
Eukaryotic - chromatin
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Bacterial transcription
Bacteria - single RNA polymerase
Promoter, bound by sigma subunit of RNA pol
Open Reading Frame (ORF)
Frame Terminator, RNA folds into hairpin
^ RNA-like strand ^
Template strand
mRNA
5' UTR (untranslated region)
ATG start codon
3' UTR
Start codons always downstream of +1
Look up: ribosome binding site
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SNRNPs < look up
snRNPs
1.) RNA pol II is recruited to promoter DNA
2.) Synthesis of primary transcript (1* transcript pre-mRNA
3.) Removal of introns (called RNA splicing) by spliceosomes. Intron released as lariat, exons are joined
4.) Enxyme catalyzed addition of 5' cap (7-methylguanilate) 3' tail
5.) Mature transcript (mRNA) moved from nucleus to cytoplasm
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Case 3 - Correction of a Pathenogenic Mutation in human embryos
Shoukhrat Hutaliou (OHSU)
Hypertrophic cardiomyopathy - inherited
Caroial disease
Caused by Mutation in many different genes
mybpc3 - cardiac myosin-binding protein C
regulation of heart muscle contraction & relaxation
Dominant phenotypic mutation
Intracytoplasmic injection
50% chance of passing on trait (dom phenotype)
CRISPR - Cas-9 editing of human embryo uniform rather than mosaic development
Odd Obsevation - Repair of DSB off of maternal allele rather than injected oligonucleotide. Unknown reason.
