Studied by 6 people
Mendel
-pea plants
-basic principles of inheritance
-ability to describe trait passing with math (predictable and consistent ratios)
-1856
Miescher
-DNA discovered (nuclein)
-isolated “nuclein” (DNA) from leucocytes
-isolating compounds and characterizing molec
-know ingredients of DNA, don’t know anything about structure or importance
-didn’t understand universal nature of inheritance and phenotype
-1868
Garrod
-identified first human genetic disease
-alkaptonuria (black urine → phenotype)more prevalent in related individuals
-hereditary situation (passed down in fam)
-1902
Hardy and Weinberg
-study allele frequencies of populations
-how traits play out in larger populations
-adding math to genetics allows predictability (expected ratios, when something deviates, know something is up)
-1908
Griffith
-transformation of bacteria occurs via a transforming agent
-S and R strains of bacteria
-genes transferred horizontally → not with generation of offspring → indicates transfer of a specific molecule
-1928
Avery, MacLeod, and McCarty
transforming agent is DNA
Hershey and Chase
-radioactive phages
-solidifies that DNA is transforming agent
-1944
McClintock
-transposable elements (moveable genes)
-mobile pieces of DNA
-maize had color ratios that were unpredictable by math → observation of ratios showed that genes were moveable
-1950
Watson and Crick
-double-helix
-sugar-phosphate backbone
-nitrogenous base on inside
-1953
Stahl
semi-conservative DNA replication (half of parent strand to code daughter strand)
Berg
-turning point for research→ start messing around with DNA
-constructed first recombinant DNA
-insert DNA from another source into plasmid
-1972
human insulin
-created with Berg’s recombinant DNA technology
-E. coli used to mass produce molecule for diabetic patients
Gilbert and Sanger
-developed DNA sequencing tecknology
-can figure out nucleotide sequence of strand
-1977
Mullis et al.
-PCR for amplification of specific DNA fragments
-basis of molecular biology
-1986
Watson et al.
-headed initiative to sequence genomes
-1990
Roslin Institute
-clones first mammal (Dolly the Sheep)
-1997
Human Genome Project
-revealed completion of the first draft genome
-2001
-about 11 years from initiation to draft
1000 Genomes Project
-2008-2010
-1000 human genomes sequenced
-catalog variation and info about disease
transmission
-punnet square genetics
-mendilian genetics
…of traits from one generation to the next
population
-analysis of heredity of traits in a group
-Hardy and Weinberg and allele frequency
-not just one family
molecular
-analysis of structure and functions of genes by zooming in on DNA and chromosomes
-genes and mutations
-underly the math
quantitative
-analysis of heredity of multigenic traits in a group
-study the numbers and whether the traits follow the trends they should
modern genetics
-genetic maps
-recombinant DNA technology
-genetics databases
-genetic basis of disease
-genomics
TATA box
general and specific transcription factors assemble here so that transcription can begin
TFIID
-first thing that binds to TATA box
-biochemically the only thing that can find the TATA box
TFIIA and TFIIB
bind to TFIID on TATA box
TFIIF
-bound to RNA polymerase
-associates with TFIIB
-biochemically: does transcription
RNA polymerase
-does transcription
-does not care about sequence using to make RNA
transcription
-making RNA from DNA
-codons are NOT related!
exons
transcribed parts of DNA (RNA) that are used for protein synethesis
introns
-non-coding sequences of RNA
-taken out (not used to make proteins)
locus
a part of DNA on a chromosome that controls a physically hereditable trait
Beadle and Tatum
-worked with Neurospora, bread mold
-one-gene-one-enzyme hypothesis
-used x-rays to form mutants → grown on complete media → grown on minimal media to observe phenotypical differences → add things back to see what amino acid needed for growth
mutagenisis
creating observable differences in a species
complete media
-contains all things a sample needs for growth
-good for getting a lot of cells for experiment
minimal media
-does not have everything needed for growth
-allows observation of phenotype
-if something doesn’t grow, missing something it needs (can’t make something it needs to live) → raises q of which gene controls this
-add things back (amino acids, minerals and vitamins) to see what missing
mutations
…in genes cause variations in protein structure and function
-can result in an altered overall phenotype
-caused by: errors during replication, environmental stimuli/pressures (chemicals, UV radiation)
adaptation theory
-adding something actively causes a mutation
-chance of mutation for resistance same every time
-applying selection pressure causes mutation
mutation theory
-mutation already exists (spontaneously arises)
-when add something, can see mutation
-random
-applying selection pressure reveals mutation
purine
-G and A
-two-ring struct
pyrimidine
-C and T
-one-ring struct
two
number of H-bonds between A and T
three
number of H-bonds between G and C
tautomerization
-of DNA bases
-natural occurrence
-DNA replication error
-affects how H-bonds form
single nucleotide polymorphisms
-DNA replication error
-right nucleotide pairs with wrong
-passed down to the next generation
-ex) G and T pair, one replication produces one mutant and one wild type
looping out errors
-DNA replication error
-displacement of a base, particularly in repetitive regions
-lots of repetition of one base makes difficult for DNA pol to read
-leads to base deletion or base insertion on new strand
-mutation depends on where error occurs in DNA
thymine thymine dimers
-environmentally induced mutation
-UV light causes covalent linking of bases
-distorts DNA
-makes polymerase interpretation difficult
intercalating agents
-chemically induced mutations
-EtBr
-sometimes used by scientists to understand mutations
-makes gaps that are randomly filled or deleted
-polymerase unsure of “gap” (intercalating agent inserted), so inserts something or deletes something
nucleotide excision repair
-primary way for UV-induced T-T dimers repaired
-errors in process can result in skin cancer
-UvrAB complex scans for distortions, section cut out, filled in by DNA pol, and ligated by DNA ligase
-constantly protecting selves from environmental damage → only notice damage when NER fails (think immune system → when fails, get sick)
methyl-directed mismatch repair
-methylated bases normal and part of DNA structure → methylation occurs after replication
-allows enzymes to know which strand is correct if find mismatch because happens so soon after replication that new strand is unmethylated → indicates that it is the thing that is wrong
Ames test
-how to tell if something is mutagenic
-creates situation where we can observe a phenotype
-identify chemicals that cause mutations
-bacteria without ability to make an amino acid → mix with rat liver enzyme → plated on medium lacking the amino acid → add chemical compound → of have bacterial growth, ability to make amino acid is restored and the chemical is mutagenic (causes mutations)
replica plating
-how to tell if mutation has occurred
-makes it easier to study auxotrophic mutants
-Beadle and Tatum → everything in tube identical
-bacterial colonies stamped from master plate onto complete (possible mutants) and minimal (no mutants) media
-if bacteria cannot grow on minimal media, mutation has occurred
-can grow if given everything it needs (complete media), but missing element of biochemical pathway to make something that it needs (minimal media)
Ac
-activator
-can activate movement of Ds
Ds
-dissociation
-present in genome
purple kernels
-C gene active
-native state
yellow kernels
-Ac activates Ds transposition into C → disrupts C gene
-induces several nucleotide disruption in coding region
spotted kernel
-Ac activates Ds transposition in and out of C gene throughout development
-Ds is mobile and can jump in and out whenever
transposable elements
-introduce genes into species with known mutants
-can’t control where the TE drops, so not super reliable
transition
-purine→purine
-pyrimidine→pyrimidine
-point mutation in DNA
-single base pair substitution
-may or may not affect aa seq
transversion
-purine→pyrimidine or vice versa
-point mutation in DNA
-single base pair substitution
-may or may not affect aa seq
missense
-base pair substitution(s) that result in coding for different aa(s)
-single or multiple aa substitutions
-severity depends on location
nonsense
-base pair substitution(s) that result in replacement with STOP codon
-truncated protein
-usually severe
neutral
-base pair substitution(s) that result in coding for a different aa(s) with similar biochemical properties
-single or multiple aa substitutions
-severity depends on location
silent
-base pair substitution(s) that result in coding for same aa(s)
-no effects
frameshift
-insertions and deletions that result in shift in ribosomal reading frame
-extensive missense
-unusually truncated protein
-usually very severe
-can describe DNA and protein
polytene chromosomes
-mega chromosomes
-result of multiple rounds of DNA replication without cell division
-huge, so easy to study chromosome structure
-Drosophila
cytokinesis
cell division
deletion (chromosome)
-chromosomal rearrangement → deletion of chromosome segment deletes hundreds of genes
-understand chromosome structure
-allows mapping of chromosome
-can result in pseudodominance
pseudodominance
-diploid organisms only
-homologous chromosomes, but one missing section → only have one set of genes for that region → nothing to mask phenotype → effectively haploid
progressive mutants
-reveals where phenotypes are because can see recessive phenotype with deleted regions
-banding patterns used to affiliate location with phenotype → phenotype highly characteristic of certain locations
tandem duplication
-duplication right next to each other
-ABCBC
reverse tandem duplication
-duplication flipped
-ABCCB
terminal tandem duplication
-replicated twice
-ABABC
duplication
-region of duplication determines effects of duplication
-duplicated banding patterns of region 16A of Drosophila chromosome leads to bar eye phenotype
inversion
-flips material around
-no additions or subtractions
-all regions are present → issue is with meiosis (reproduction)
-paracentric or pericentric
paracentric inversion
-does not include centromere
-inversion loop during prophase I to match sequence
-dual centromeres
-result in acentric fragment (lost), dicentric bridge (dual centromeres, splits in random place when chromosomes pulled apart in anaphase I)
-get two deletion products missing genetic material and one normal product and one inversion product with all genes present
-50% viability
pericentric inversion
-includes centromere
-inversion loop
-get viable normal product
-get two deletion/duplication products (1/2 of one missing, one region missing in another)
-get viable inversion product where all genes present
-50% viability
translocation
-change position of certain chromosome segments
-three types
-implicated in some cancers
-PCR reveals where gene is (should be far apart of diff chromosomes, but if reciprocal translation, then close)
nonreciprocal intrachromosomal translocation
within same chromosome, genes move to different location
nonreciprocal interchromosomal replication
different chromosome, genes move from one chromosome to another with completely different genes
reciprocal interchromosomal translocation
different chromosomes, genes exchanged
