BIOL 112 Lecture Notes - Lecture 7: Archibald Garrod, Frederick Sanger, Edward Tatum

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BIOL 112- Lecture 16- Genetic Code
The key to DNA
!The sequence of nucleotides not constrained by the structure. DNA can
accommodate any sequence. An arbitrary sequence can encode information.
!The two strand of DNA encode the same information in complementary form
suggesting a method replication
Genotype to phenotype:
Archibald Garrod:
!Provided first evidence that the genetic code is coding for proteins
!He analyzed urine samples of people with alkaptonuria (when urine appears
black due to alkapton)
o!He showed that alkaptonuria is recessive
!!Almost all affected parents gave rise to unaffected progeny
" not dominant
o!Thought problem was inborn error of metabolismcausing lack of
thyrosine-metabolizing enzyme
!!This lead him to hypothesize that enzymes are under control
of the hereditary material, and thus an error in the hereditary
material resulted in an error in an enzyme
George Beadle and Edward Tatum:
They clarified the relationship between gene
and phenotype and reasoned that if genes
code for proteins and each step in the
metabolic pathway is catalyzed by a different
enzyme, mutants lacking enzymes wouldnt be
able to produce compounds later in the
pathway
!Mutants could be rescued by providing
missing components in the growth
media
Worked with neurospora, isolated auxotroph
and prototroph
!Auxotroph: mutant organism that requires an additional nutrient that the wild
type doesn’t
!Prototroph: wild type organism that doesnt require additional nutrients
Thought that one or more enzymes that synthesized arginine was defective
!Pathways to make arginine includes ornithine, citrulline and arginine
They were able to identify the enzyme in the pathway that was missing in a mutant
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!Could only grow in media supplemented by compounds downstream of the
blocked step
Found that a lack of a particular enzyme corresponded to a mutation in a specific
gene
!Concluded that a gene acts by directing the production of only one enzyme
!Led to the ONE GENE, ONE ENZYME hypothesis
o!Modified to ONE GENE, ONE PROTEIN hypothesis, since some enzymes
have more than one protein and not all proteins are enzymes
Fred Sanger:
Determined the first peptide sequence of a protein: INSULIN
!Seemed reasonable that DNA encoded the peptide sequence
Crick, Sydney Benner and François Jacob: Proposed the
central dogma- The idea that genetic information flows
from DNA to RNA to protein, in a unidirectional way
So, the first step from genotype to phenotype is the
formation of the messenger RNA. Of course, RNA is very
much like DNA in structure with a few minor variations. RNA
has uracil instead of thymine, but uracil pairs with adenine
so that's a technicality. Also, RNA has a 2' hydroxyl that
DNA doesn't have, which has no effect as far as we are
concerned.
RNA still has the same sugar
phosphate backbone as
DNA, follows base-pairing
rules when synthesized using
a DNA template and, as we
saw with the primers, RNA
forms a double stranded
helix when paired with DNA
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Thus, just as the information from one strand of
DNA can easily be copied to the antiparallel
strand during DNA synthesis, the information
from a strand of DNA can easily be transferred
to a complementary strand of RNA. This occurs
when an enzyme, RNA
polymerase, sits down
on DNA at the
beginning of a gene,
unwinds the DNA and
starts creating a strand
of RNA complementary
to the DNA. The RNA
polymerase extends the
RNA strand until it gets
to the end of the gene.
Transcription:
Process of creating the RNA strand
RNA polymerase starts at DNA at the beginning of a
gene, unwinds it and creates its complimentary strand:
-!RNA polymerase vs DNA polymerase:
o!RNA doesn’t need a 3hydroxyl to get
started
-!It incorporates triphosphate ribonucleiotides
instead of deoxyribonucleiotides
-!END RESULT: mRNA (messenger RNA)
-!RNA polymerase knows where to start and stop: mRNA strand starts/ends slightly
before/after the stretch of DNA that actually codes the protein
-!When the RNA leaves the nucleus, and enters the cytoplasm, it carries all the info
that the protein synthesis machinery needs to make the protein encoded by that
gene
DNA
RNA
Deoxyribose sugar
Ribose sugar
Double stranded
Single stranded
Adenine pairs with
Thymine (has a
methyl group on its
1’ carbon)
Adenine pairs with
uracil (does not
have a methyl
group on 1carbon)
Resides in the
nucleus
Resides in both the
nucleus and the
cytoplasm
Has a hydrogen at
its 2C
Has a hydroxyl
group on its 2’ C
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BIOL 112 Full Course Notes
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Document Summary

The sequence of nucleotides not constrained by the structure. The two strand of dna encode the same information in complementary form suggesting a method replication. Archibald garrod: provided first evidence that the genetic code is coding for proteins, he analyzed urine samples of people with alkaptonuria (when urine appears black due to alkapton) o he showed that alkaptonuria is recessive. Almost all affected parents gave rise to unaffected progeny. Not dominant o thought problem was inborn error of metabolism causing lack of thyrosine-metabolizing enzyme. This lead him to hypothesize that enzymes are under control of the hereditary material, and thus an error in the hereditary material resulted in an error in an enzyme for proteins and each step. Worked with neurospora, isolated auxotroph and prototroph: auxotroph: mutant organism that requires an additional nutrient that the wild type doesn"t, prototroph: wild type organism that doesn"t require additional nutrients.

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