Review

Some terms• Gene – section of DNA that encodes a

trait– Trait – characteristic (Ex. Eye color)

• Allele – different varieties of a gene– Example: brown eye color

• Because human cells are diploid, we have 2 alleles for each gene– alleles are the same – homozygous– alleles are different – heterozygous

• Whatever combination of alleles are present is called the genotype

• The outward appearance of those alleles is called the phenotype

Punnett square• Alleles can be either– Dominant (is observed) – express as a capital letter– Recessive (is not observed) – express as a lower case letter

• Example (Mendel’s experiment)– Purple flowers (PP)

• What is the phenotype?• What is the genotype?

– White flowers (pp)• What is the phenotype?• What is the genotype?

– What happens when we cross these two plants?• Cross means to have an organism sexually reproduce with another

organism• Punnett square helps us answer this question

Punnett square

Pp Pp

Pp Pp

P P

p

p

• Separate the phenotype into the gametes it can produce– PP -> P or P– Pp -> p or p

• Gray boxes = parental generation (P generation)• F1 generation = offspring of the parental generation– What is the phenotype of the F1 generation?– What is the genotype of the F1 generation?

• If you were to cross the F1 generation with itself = F2 generation

Punnett square

PP Pp

Pp pp

P p

P

p

• Separate the phenotype into the gametes it can produce– Pp -> P or p– Pp -> P or p

What are the phenotypes of the F2 generation?What are the genotypes of the F2 generation?What is the ratio of phenotypes?What is the ratio of genotypes?What is the probability that you will have a purple flower based on the F1 cross?

Mendel’s Laws

• 1st law – law of segregation– We’ve already seen this when we made our

punnett square– Alleles separate during the formation of gametes,

so that half will carry one copy and the other half the other copy

• 2nd law – law of independent assortment– Genes located on different chromosomes are

inherited independently of one another– Example: eye color and hair color

Law of segregation

P p

meiosis

P

p

P

p

Law of Independent Assortment

P pmeiosis

P

p

P

pW w

W

w w

W

P pmeiosis

P

p

P

pw W

w

W W

w

Some traits don’t follow Mendel’s laws

• Many traits are determined by multiple genes = polygenic– Example: height– Distribution of phenotypes = continuous variation

Some traits don’t follow Mendel’s laws

• Pleiotropy = when one gene affects multiple phenotypes– Example: gene that makes phenylalanine hydroxylase

affects brain development AND skin color• Incomplete dominance– Both alleles are expressed – The expression of one affects the expression of the

other• Can think of this as phenotype averaging

– Example: japanese four o’clock flowers• RR = red flower• WW = white flower

Incomplete dominance

RW RW

RW RW

R R

W

W

• Separate the phenotype into the gametes it can produce– RR -> R or R– WW -> W or W

• F1 generation = offspring of the parental generation– What is the phenotype of the F1 generation?– What is the genotype of the F1 generation?

Some traits don’t follow Mendel’s laws

• Codominance– Both alleles are expressed – The expression of one does not affect the expression

of the other– Example: human blood types

• AA = type A blood – galactosamine added to plasma membrane of red blood cells

• BB = type B blood – galactose added to plasma membrane of red blood cells

• AB = type AB blood – galactose and galactosamine added to plasma membrane of red blood cells

• OO = type O blood – nothing is added to red blood cells

Codominance

AA

A

BB

B

AB

BA

Chromosomes are responsible for all this inheritance

• Sex-Linked traits– Humans have 23 pairs of chromosomes• 22 pairs of chromosomes are identical in their genes

(not their alleles) – called autosomes• 1 pair is not identical and helps determine sex – called

sex chromosomes– Males = XY– Females = XX

karyotype

Determination of sex

XX XX

XY XY

X X

X

Y

• Half male, half female• Sex Linked traits – genes that are located on sex

chromosomes (Example: baldness)– XB – full head of hair– Xb - bald

XBXB XBXb

XBY XbY

XB Xb

XB

Y

Nondisjunction• Nondisjunction – when chromosomes fail to separate

properly during meiosis• This leads to abnormal number of chromosomes =

aneuploidy– If chromosome is lost (one copy = monosomic) = individual does

not survive– If chromosome is gained (3 copies = trisomic) = individual may

survive but only in a few cases and will be mentally impaired• Example: Trisopy 21 (Down syndrome)

• Non disjunction of sex chromosomes– XXY – Klinefelter Syndrome – sterile male with many female

characteristics– X – Turner Syndrome- Mentally impaired females, short stature

Mutations

• Accidental change in the DNA sequence– Breaks in DNA (X-rays)– Copied incorrectly (UV light)

• Mutations often causes harmful effects = genetic disorder– More often recessive because function of normal

proteins is lost – so the good copy can make up for it

• Scientists use pedigrees to help determine how a mutation is inherited

Two types of mutations

• Point mutation – One nucleotide is replaced with a different nucleotide (Example: A is replaced with G)

• Frame-shift mutation – A nucleotide is added or removed (Example: ATGCGA becomes ATGGA)– Causes a bigger change usually because

everything downstream of the mutation is altered

Normal Replication

A T G C A T G C A T G CT A C G T A C G T A C G

DNA

DNA

Point Mutation

A T G C A T G C A T G CT A C G T G C G T A C G

DNA

DNA

Frame shift Mutation

A T G C A T G C A T G CT A C G T C G T A C G

DNA

DNA

Pedigree

Normal female

Sickle Cell Anemia – point mutation

• Recessive disorder– SS – normal– Ss – normal– Ss – sickle cell anemia – difficulties in transporting

oxygen to the body– When we get to evolution, we’ll see there is an

advantage to having this allele

BREAK

What’s the genetic material

• Griffith experiment1. Live S bacteria kill mice2. Live R bacteria do NOT kill mice3. Heat-killed S bacteria do NOT kill mice4. Heat killed S bacteria + Live R bacteria??

Griffith Experiment

S X R

SXSXR X

R was transformed by something in S

Avery and Hersey-chase Experiments

• 1944– Avery – Repeated Griffith experiment, but they removed all the

protein from the dead S bacteria• Still saw the same result, so it must not be the protein

• 1952– Hershey-Chase

• Labeled DNA with radioactive phosphate• Labeled proteins with radioactive sulfur• Let viruses grow in the presence of either radioactive DNA or

radioactive protein• Let the viruses infect bacterial cells• Removed the viruses and just looked at the bacterial cells to see

which ones had radioactivity– Bacteria that were exposed to viruses with radioactive DNA had radioactivity– Bacteria that were exposed to viruses with radioactive protein did not have

radioactivity

Hershey-Chase experiment

P S

protein

?DNA is the genetic material

How does DNA replicate?Structure of DNA helps

• Chargaff’s Rule – Measured the amount of

A,T,C, and G– Found that the amount of A

always equaled the amount of T (same applied for C and G)

• Double helix discovered by Rosalind Franklin, Francis Crick, and James Watson

• Minor groove• Major groove

How does DNA replicate? Meselson-Stahl experiment

• 3 possible explanation for how DNA is replicated– Conservative replication

• original DNA is split in half• Each half is copied• Original DNA is rejoined (both strands are old) and new copy is

joined together (both strands are new)– Semiconservative replication

• Original DNA is split in half• Each half is copied• Original DNA stays with new copy (one strand is old and one is

new)– Dispersive replication

• Original strand is split in half and then further divided into sections• Sections are split between both old and new strands

3 possible explanations

Meselson-Stahl experiment• Grow up some bacteria• Let one round of replication happen with heavy DNA• Let a second round of replication happen with normal

DNA (light DNA)– If conservative

• First round – 2 types: heavy AND light• Second round – 2 types: heavy and light

– If semiconservative• First round – 1 type: average• Second round – 2 types: light AND average

– If dispersive• First round – 1 type: average• Second round – 1 type: somewhere between average and light

Messelson-Stahl experimentNormal DNA (light)

Heavy DNA (heavy)

1st round cells are made with heavy DNA

2nd round cells are made with light DNA

DNA replication• Helicase – enzyme that unzips the DNA

– The region where the DNA is unzipped is called the replication fork

• DNA polymerase – copies both strands of DNA at the same time– Needs a primer – section of DNA that starts the new strand– Always copies from 5’ -> 3’

• One strand is easy to copy because replication is moving in the same direction as DNA polymerase – this new strand formed is called the leading strand

• One strand is difficult to copy because replication is moving opposite to the direction of DNA polymerase – this new strand is called the lagging strand– Must be made in segments– Segments are later joined together by another enzyme - DNA ligase

Normal Replication

A T G C A T G C A T G CT A C G T A C G T A C G

DNA

DNA5’

5’

3’

3’

Helicase is an enzyme that unzips the DNADNA polymerase copies the DNA

A T G C A T G C A T G C

DNA 5’

3’

3’

T A C G T A C G T A C G

DNA5’

helicase

DNA polymerase

T A C G T A C G T A C G

DNA5’ 3’

Leading strand

Helicase is an enzyme that unzips the DNADNA polymerase copies the DNA

A T G C A T G C A T G C

DNA 5’

3’

3’

T A C G T A C G T A C G

DNA5’

DNA polymerase

T A C G T A C G T A C G

DNA5’ 3’

Replication is moving the direction of the red arrow. DNA must be made from 5’ -> 3’ direction. Problem!! The orientation of the top strand doesn’t allow this.

Helicase is an enzyme that unzips the DNADNA polymerase copies the DNA

3’

T A C G T A C G T A C G

DNA5’

How could we get around this problem?

Would be easy if we could just flip it..so that’s sort of what our cells do.

1. DNA loops around2. DNA primer is attached to DNA3. DNA polymerase copies DNA – called

the lagging strand4. Because of the loop, the DNA can only

be copied in segments – called Okazaki fragments

5. DNA ligase joins the segments together

DNA ligase