Chapter 16: The Molecular Basis of Inheritance
Dec 23, 2015
Essential Knowledge
3.a.1 – DNA, and in some cases RNA, is the primary source of heritable information (16.1 & 16.2).
3.c.1 – Changes in genotype can result in changes in phenotype (16.2).
Question? Traits are inherited on chromosomes,
but what in the chromosomes is the genetic material?
Two possibilities: Protein DNA
Qualifications Protein:
Until 1940s, evidence for protein was STRONG!
Very complex structureHigh specificity of function
DNA:Simple structureNot much known about it (early 1900’s)
Result Something turned the R cells into S cells (in
4th experiment) Transformation - the assimilation of
external genetic material by a cell And…the pathogenic trait was inherited by all
new offspring!
Problem Griffith used heat
Heat denatures proteins DNA – heat stable
Then, could proteins still be the genetic material?
Griffith’s results were contrary to accepted views
Avery, McCarty and MacLeod - 1944
Repeated Griffith’s experiments, but added specific fractions of S cells
Result - only DNA transformed R cells into S cells
Avery, cont. Experiment not believed
Why? Scientists thought bacteria make-up was
considerably different from humans/other living organisms
Hershey- Chase 1952 Genetic information of a virus or phage Phage
Virus that attacks bacteria and reprograms host to produce more viruses (by injecting its own DNA)
Virus Intro DNA and/or RNA core Enclosed by envelope
Made of protein To reproduce, a virus must attach to a cell
and inject its genetic info (either RNA/DNA) INTO the cell
Phage Components Hershey/Chase knew viruses reproduced, but
didn’t know what was injected… Two main chemicals:
Protein DNA
Hershey/Chase used tracers Radioactive isotope tracers Protein - CHONS, can trace with 35S DNA - CHONP, can trace with 32P
Experiment Used phages labeled with one tracer or the
other and looked to see which tracer entered the infected bacteria cells
Hershey - Chase movie
Result DNA enters the host cell, but the protein did
not Therefore, DNA is the genetic material that is
passed down
Watson and Crick - 1953 Used X-ray crystallography data Used model building Result - Double Helix Model of DNA structure
One page paper, 1953
Rosalind Franklin Also used x-ray crystallography Determined DNA had two strands Died in 1958 Her colleague got Nobel Prize (because
Franklin published under his name!)
DNA Composition Made of nucleotides: (3 parts)
1. Deoxyribose Sugar (5-C ring)2. Phosphate (PO4-)
3. Nitrogen Bases: A,T,C,G• Purines: A,G• Pyrimidines: C,T
DNA Backbone Polymer of sugar - phosphate 2 backbones present Phosphate of one nucleotide is attached to
sugar of the next Alternates sugar-phosphate
Nitrogen Bases Bridge the backbones together Purine + Pyrimidine = 3 rings
Keeps a constant distance between the 2 backbones
Nucleotide held together by H-bonds
Chargaff’s Rule Studied chemical composition of DNA Found:
the nucleotides were found in certain ratios % composition differed between species
Watson and Crick Published a second paper (1954) that
speculated on the way DNA replicates Proof of replication given by others
Replication The process of making more DNA (from
existing DNA) Completed during S-phase of Interphase
Problem: When cells replicate, the genome must be copied exactly How is this done?
Models for DNA Replication
1. Conservative – one old strand, one new strand
2. Semiconservative – each strand is 1/2 old, 1/2 new
3. Dispersive – strands are mixtures of old and new
Meselson - Stahl late 1950’s
Grew bacteria on two isotopes of N Started on 15N, switched to 14N Looked at weight of DNA after one, then 2
rounds of replication Results:
Confirmed the Semiconservative Model of DNA replication
Parent strand serves as a template
Replication - Preview DNA splits by breaking the H-bonds
between the backbones. Then DNA builds the missing
backbone using the old backbone as a template.
DNA is replicated in only a few hours.
Origins of Replication Specific sites on the DNA molecule that start
replication. Recognized by a specific DNA base sequence. Proteins/enzymes initiate replication
Prokaryotic replication Ex: bacteria (E. coli) Circular DNA 1 origin site Replication runs in both directions from the
origin site
Eukaryotic replication Many origin sites.
100s/1000s Replication bubbles fuse to form new DNA
strands. Faster replication (usually) Replication also runs in both directions from
origin site
DNA Elongation Done so by DNA Polymerases Adds DNA triphosphate monomers to the
growing replication strand These triphosphate contain the complementary
nucleotides Matches A to T and G to C
Energy for Replication Exergonic rxn Comes from the triphosphate
monomers. Loses two phos as each
monomer/nucleotide is added. Similar to ATP cycle
ATP contains ribose sugar DNA = deoxyribose
Problem of Antiparallel DNA
The two DNA strands run antiparallel to each other
Two “ends” of strand 3` - sugar/OH end 5` = phosphate end
New DNA strand can only elongate in the 5` 3` direction Old DNA strand 3’ 5’
Leading Strand Continuous replication toward the
replication fork in the 5`3` direction Leading strand is a NEW strand that’s being
added
Lagging Strand Discontinuous synthesis away from the
replication fork Replicated in short segments as more
template becomes opened up Lagging strand is also NEW!
Replication fork animation
Priming DNA Polymerase cannot initiate DNA
synthesis (by itself) Nucleotides can be added (only to an existing
chain). This nucleotide chain is called a primer
Primer Made of RNA 10 nucleotides long Added to DNA by an enzyme called primase DNA is then added to the RNA primer (to
finish replication) A primer is needed for each DNA elongation
site This is called “Priming”
Enzymes DNA Ligase - joins all DNA fragments
together Helicase - unwinds the DNA double helix DNA polymerase – elongation, replacement
of RNA primer with DNA
Other Proteins in Replication
Single-Strand Binding Proteins - help hold the DNA strands apart
Primase – priming (adds RNA section to existing chain)
DNA Replication Error Rate
1 in 10 billion base pairs About 3 mistakes in our DNA each time it’s
replicated
Reasons for Accuracy DNA Polymerase self-checks and corrects
mismatches DNA Repair Enzymes - a family of enzymes
that checks and corrects DNA Replication overview
DNA Repair 50+ different DNA repair enzymes known Failure to repair may lead to cancer or other
health problems Ex:
Xeroderma Pigmentosum -Genetic condition where a DNA repair enzyme doesn’t work
UV light causes damage, which can lead to cancer
Thymine Dimers T-T binding from side to side causing a
bubble in DNA backbone Often caused by UV light
Excision Repair Cuts out the damaged DNA DNA Polymerase fills in the excised area with
new bases DNA Ligase seals the backbone
Problem - ends of DNA DNA Polymerase can only add nucleotides in
the 5` 3` direction Therefore, it can’t complete the ends of the
DNA strand Result:
DNA gets shorter and shorter with each round of replication
Telomeres Repeating units of TTAGGG (100- 1000 X)
at the end of the DNA strand Protects DNA from unwinding and sticking
together Telomeres shorten with each DNA
replication
Telomeres Serve as a “clock” to count how many times
DNA has replicated When the telomeres are too short, the cell
dies by apoptosis
Implication Telomeres are involved with the aging
process Limits how many times a cell line can divide
Telomerase Enzyme that uses RNA to rebuild
telomeres Can make cells “immortal”
Found in cancer cells Found in germ/sex cells
Limited activity in active cells (such as skin cells)
Control of telomerase may stop cancer, or extend the life span
Summary Recognize scientists and the experiments that lead to
the understanding of the molecular basis of inheritance.
Identify the double helix composition and structure of DNA.
Identify the process and steps of DNA replication. Recognize the problems in replicating the ends of the
DNA molecules. Give an example of DNA proofreading and repair. Gain familiarity with the packing of DNA into a
Eukaryotic chromosome.