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The journey from DNA to phenotype
Question 1 - How are
traits inherited?
Gregor Mendel - initiated studies that would open up
Darwin’s “black box”
-Presented work on heredity in 1865
-Attempted to demonstrate the usefulness of laws of heredity for
evolution, was ignored
Mendel and the Garden Pea
• Gregor Mendel performed experiments
with garden peas
– peas are ideally suited to the study of
heredity
• many varieties are available with easily
distinguishable traits that can be quantified
• they are small, easy to grow, and produce large
numbers of offspring quickly
• their reproductive organs can be easily
manipulated so that pollination can be
controlled
• they can self-fertilize
Mendel’s basic experimental
design
Mendel’s first experiment on Heredity
- Do Peas “Breed True”
Yes. Traits are inherited from parents to offspring
- Why was this necessary?
Mendel’s second experiment:
-Bread varieties with different
traits
-Carried out breeding for multiple
generations (F1, F2…)
-Found that one trait was lost
during F1 generation, but returned
in lower numbers in F2 generation
3:1 (75%:25%)
-Concluded that each trait has 2
“factors”
-Concluded that each “factor”
segregates independently
during formation of sex cells (1st
law of heredity)
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Mendel’s third experiment:
-Bread varieties with multiple
alternative traits
-Observed 9:3:3:1 ratio, including
new combinations of traits
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-Concluded that traits are
independently assorted. 2nd law of
heredity.
-(This law isn’t always correct, and
probably shouldn’t be called a law)
Mendel’s conclusions
• Hypothesis 1
– parents do not transmit traits directly to their offspring
– parents transmit information about the trait in the form of
what Mendel called factors
• in modern terms, Mendel’s factors are called genes
• Hypothesis 2
– each parent contains two copies of the factor governing each
trait
– the two copies of the factor may or may not be the same
• homozygous individuals have two of the same copies
• heterozygous individuals have two different copies
Mendel’s conclusions
• Hypothesis 3
– alternative forms of a factor lead to alternative traits
– alleles are defined as alternative forms of a factor
– appearance is determined by the alleles an individual
receives from its parents
• the alleles present are the individual’s genotype
• the expression of the alleles is the appearance or phenotype
Mendel in current knowledge
• We now know that genes are carried on chromosomes, with
different alleles on the different homologues.
• The location of a gene on a chromosome is called its locus.
Figure 11.6 Alternative alleles of genes are located on homologous chromosomes
Mendel’s Laws
– Mendel’s First Law: Segregation
• the two alleles of a trait separate from each
other during the formation of gametes, so that
half of the gametes will carry one allele and half
the gametes will carry the other allele
Mendel’s laws
– Mendel’s Second Law: Independent
Assortment
• genes located on different chromosomes are
inherited independently of one another
Not all traits show “Mendelian
inheritance”
• Often the expression of phenotype is
not straightforward
• Continuous variation
– characters can show a range of small
differences when multiple genes act jointly
to influence a character
• this type of inheritance is called polygenic
Height is a continuously varying
character
Why Some Traits Don’t Show
Mendelian Inheritance
• Environmental effects
– the degree to which many alleles are
expressed depends on the environment
– for example, some alleles are heatsensitive
• arctic foxes only produce fur pigment when
temperatures are warm
Environmental effects on an
allele
Mendel was ignored because the mechanism of heredity was
unknown
-Darwin’s black box was Mendel’s black box too
-Mendel’s results were replicated by 3 others in 1900, geneticists started
taking Mendel seriously
-Question 2 - Where are the genes
within a cell?
-Walter Sutton published “The chromosomes in heredity” in 1903
“Gene Linkage” occurs when two genes reside on the
same chromosome - violates the 2nd law of heredity
- Gene linkage can be broken
by “crossing over” during
meiosis
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Chromosome mapping
-Morgan and undergrads looked at “mutations” in fruit flies
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-Could use the frequency of “recombinants” (broken linkage groups) to
estimate the relative positions of genes on a chromosome
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Breaking gene Linkage
-Morgan et al. helped establish that genes reside on
chromosomes.
Could map the relative distance of genes on a chromosome
Could explain all of Mendel’s results with genetics (Morgan) and
cytology (Sutton)
-Morgan was not taken seriously by classic biologists.
Where do mutations come from?
Are “fruit fly” mutations significant enough for large scale
evolution?
By the mid 1900’s biologist could say
-Genes segregate independently in sex cells
-Genes reside on chromosomes
-Give a relative position to genes on chromosomes
-Could explain much of Darwin’s black box by genes on chrom., inherited
by offspring with crossing over, mutation
Question 3 - What are genes?
- DNA or Protein? (Chromosomes are made of both)
- Genes must be able to self replicate to allow heredity
Various observations suggested that genes are correlated to with
enzymes……..
……..Do genes control enzymes, are enzymes synthesized by
genes?
Heat killed bacteria particles can “transform” living bacteria
(1944) Avery, MacLeod, McCarthy - Transforming particle is DNA:
-Purified DNA from extract could transform, purified protien could not
-Treatment of DNA with DNAse inhibits transformation, protinase does not
Question 4: How does DNA encode genetic information?
What is the structure of DNA?
X-Ray diffraction photograph
Discovering the Structure of DNA
• Rosalind Franklin’s work in 1953 using
X-ray diffraction revealed that DNA had a regular
structure that was shaped like a corkscrew, or helix
• Francis Crick and James Watson elaborated on the
discoveries of Franklin and Chargaff and deduced
that the structure of DNA was a double helix
– two strands of DNA bound together by hydrogen bonds
between the bases
The DNA double helix
DNA is a double stranded helical molecule
-Strands held together by
hydrogen bonds
-Bases pair with specific
partners adinine:thymine,
guanine:cytosine
-There are the same
number of Gs and Cs, As
and Ts
-Base pairing had been
previously predicted from
nucleotide ratios
Double stranded molecule also suggested that
each strand could serve as a template during
replication
Hypothetical models for DNA synthesis:
Favored
model
How the DNA Molecule Copies
Itself
• Matthew Meselson and Franklin Stahl
tested, in 1958, the three alternative
hypotheses for the replication of DNA
– they used radioactive isotopes of N to label
DNA at different stages of replication
– they found that DNA replication was semiconservative
What are the predictions
from each hypothesis?
Strands of DNA are directional
Building the leading and lagging
strands
The Role of Mutations in Human
Heredity
• Accidental changes in genes are called
mutations
– mutations occur only rarely and almost
always result in recessive alleles
• not eliminated from the population because
they are not usually expressed in most
individuals (heterozygotes)
• in some cases, particular mutant alleles have
become more common in human populations
and produce harmful effects called genetic
disorders
2 mechanisms of Mutation
• There are two general ways in which the genetic message
encoded in DNA can be altered
– mutation
• results from errors in replication
• can involve changes, additions, or deletions to nucleotides
– recombination
• causes change in the position of all or part of a gene
Mutation
• Mutations can alter the genetic message and affect
protein synthesis
– because most mutations occur randomly in a cell’s DNA,
most mutations are detrimental
– the effect of a mutation depends on the identity of the cell
where it occurs
• mutations in germ-line cells
– these mutations will be passed to future generations
– they are important for evolutionary change
• mutations in somatic cells
– not passed to future generations but passed to all other somatic
cells derived from it
Base substitution mutation
Mutation are the ultimate source of
variation for evolution
• All evolutionary change begins with
alterations in the genetic message
– mutation and recombination provide the
raw materials for evolution
The journey from DNA to phenotype