Chromosomes

& Cellular
Reproduction
(mitosis & meiosis)
 what is life?
 in 2 biological
dimensions?



mitosis

 

meiosis
The Blind Man’s Riddle
 Basic Cell Types:
Structure
& Evolutionary Relationships
• 2 major types of organisms
1) prokaryotes – simple cell structure
2) eukaryotes – nucleus + organelles
 Basic Cell Types:
Structure
& Evolutionary Relationships

• 5 KINGDOMS of organisms
1) prokaryotes – eubacteria & archaea
2) protists – single-celled animals
3) fungi
4) plants
5) animals
comparing prokaryotic
& eukaryotic cells
 in eukaryotic cells
DNA + histones = chromatin
 Cell Reproduction
• mostly via mitosis
(eukaryotes) or “binary
fission” (prokaryotes)
• but sometimes via meiosis
(eukaryotes)
Prokaryotic Cell Reproduction

DNA replication

segregation

cytokinesis
 prokaryotic cells (organisms)
reproduce by simple division

BINARY FISSION
Eukaryotic Cell Reproduction
eukaryotic cells (diploid)
have multiple pairs of chromosomes

homologous
pair
eukaryotic chromosome structure
How big is it? long, short, …
Where’s the centromere?

short arm
long arm

describing chromosomes
The Cell Cycle & Mitosis

DNA
 G1 phase
• period between the beginning of inter
phase and the beginning of the DNA
synthesis.
• It is the longest phase and constitutes
• up to 50% of the total inter phase duration.
Major events
• Marked protein and RNA synthesis
• Increase the cell volume by imbibing water
and nutrients
 S phase
• period between G1 and G2 phases
• DNA synthesis takes place (chromosomes
replicate)
• These duplicated structures-sister
chromatids pairs, each contains two
identical chromosome copies.
• RNA and protein synthesis are very low.
 G2 phase
• period between S and M phases
or
• between termination of DNA synthesis and
beginning prophase of the cell division.
• There is considerable amount of RNA and
protein synthesis takes place in this
phase.
mitosis
 Mitosis (Fleming 1882)
• Disjunction of duplicated chromosomes
and division of the cytoplasm to produce
two genetically identical daughter cells
 mitosis

2n=4 2n=4 2n=4

 2n=24

2n=4 “4n”=8 2n=4 & 2n=4

 The Cell Cycle & Mitosis

chromosomes and DNA molecules

elements of the spindle
 modern model
for chromosome movement
 regulation
of the cell cycle
at various
checkpoints
involving
cyclins, CDKs,
etc
What use is sex?
Genetic Recombination
&
Genetic Variation

meiosis
(production of gametes)
&
fusion
(of gametes)
 Meiosis
• Meiosis is the two successive nuclear
divisions (with corresponding cell
divisions) that produces gametes in
animals) or sexual spores (in plants and
fungi) having one-half of the genetic
material of the original cell.
2n=4 n=2 n=2
 Meiosis Prophase I

Leptotene: These cells and nuclei are usually bigger than the other cells, like a
“bouquet”
Zygotene: Pairing of homologous chromosomes begins. It is also called
synapsis and the resulting structure synaptic complex
Pachytene: The pairing stabilizes. The number of synaptic complexes corresponds
to the number of chromosomes in a haploid set of the respective species.
The pairs are also called bivalents.
Diplotene:The bivalents separate and formed cross-like structures, single or
multiple loops: the chiasmata (sing. chiasma).
Diakinesis:The chromosomes condense and become more compact.
2n=4 2n=4
2n=4 2n=4
 2n=12

2n=4 2n=4
2n=4 n=2 n=2
n=2 n=2 n=2 n=2
n=2 n=2 “2n”=4 “2n”=4
n=2 n=2 n=2 n=2
n=2 n=2 n=2 n=2
 crossing over
generates
genetic variation
 homologous
chromosomes
crossing over at pairing
after DNA synthesis

}
}
sister chromatids
sister chromatids
nonrecombinant

recombinant

recombinant

nonrecombinant
Compare Mitosis and Meiosis!
 Some Numericals

• A cell of genotype Aa undergoes mitosis. What

will be the genotypes of the daughter cells?

• A cell of genotype Aa undergoes meiosis. What

will be the genotypes of the daughter cells, if all
of them are functional?
• A given individual is heterozygous for two
pairs of alleles that are located on the
same homologous chromosome pair, A
and B on one chromosome with a and b
located on the homologous chromosome
(i) how many gamete types can such an
individual produce if there is no crossing
over (ii) what will be those types?
• A given individual is heterozygous for two
pairs of alleles that are located on the
same homologous chromosome pair, A
and B on one chromosome with a and b
located on the homologous chromosome
(i) how many gamete types can such an
individual produce if there is crossing
over (ii) what will be those types?
• A diploid individual having 24 chromosomes in a
somatic cell, how many of each of the following
is present in each cell at the stage of mitosis or
meiosis indicated?
(i) centromeres at anaphase
(ii) centromeres at anaphase I
(iii) chromatids at metaphase I
(iv) chromatids at anaphase
(v) chromosomes at anaphase
(vi) chromosomes at metaphase I
(vii) chromosomes at the close of telophase I
(viii) chromosomes at telophase II.
48, 24, 48, none, 48, 24, 12, 12
• 14. How many different gamete genotypes will
be produced by individuals of the genotypes, if
all genes shown are on different chromosomes
pairs?
(i) AA
(ii) Aa
(iii) AaBB
(iv) AaBb
(v) AabbCc
(vi) AaBbCcDdEe
Basic Principles
of Heredity
(Mendel’s laws)
 what is life?
 sometimes
it takes two


 
The Genetics of Red Hair
 Mendel:
The Father of Genetics
Mendel’s Success – Seven Traits

pea (Pisum sativum L.)

Genetic Terminology
trait
• a sequence of DNA (RNA)
• a transcriptional unit - DNA
• an allele (form of a gene)
protein • a locus (a place
on a chromosome)
RNA • a theoretical factor
that explains the results
of breeding experiments
DNA • or a tiny piece of meat
(or vegetable matter)
 e.g., A or a

1
or A , 2
A , 3
A ,...
e.g., the A locus
the R locus
e.g., AA, Aa or aa
 Aa
AA, aa
 e.g., dominance

AA = Aa = A–  A phenotype
dominant phenotype
aa  a phenotype
recessive phenotype
Monohybrid Crosses
RR rr

peas in a pod

all Rr
Principle of Particulate Inheritance

Rr


3R–:1rr
Principle of Dominance
again, in terms of the life cycle
 
TB – true TB – true
breeding segregating breeding
 no overall
effect of Rr
crossing over
at this level

NCO CO
between between
R locus & R locus &
centromere centromere

R R r r R r R r
 Mendel’s First Law

The Law of Segregation

“The separation of paired gene (alleles)
from one another and their distribution
to different sex cell”.
P RR  rr

F1 Rr

F2 1RR:2Rr:1rr
round 3R–:1rr wrinkled
 gametic array
R r
gametic array

R RR Rr
zygotic
array
r Rr rr

Punnett Square
 (3R–:1rr)

Mendel’s First Law

The Law of Segregation
 genotypic
segregation
(1RR:1Rr:1rR:1rr)
phenotypic complete
segregation 3R–:1rr dominance
   
F3 all RR 1RR:2Rr:1rr all rr
round 3 round : 1 wrinkled wrinkled
 Mendel’s First Law
the monohybrid cross
binomial expansion
F1 gametes 1R : 1r
F2 geno seg (1R : 1r)2
= (1R : 1r)  (1R : 1r)
=1RR : 1Rr : 1rR : 1rr
= 1RR : 2Rr : 1rr
F2 pheno seg = 3R– : 1rr
the R locus – at the molecular level
starch if R– excess
sucrose if rr

enzyme

mRNA RNA

R r
 the
Monohybrid
Testcross
or F1 selfed
or testcross
 regardless of type
of gene action

e.g., F1 selfed
e.g.,testcross
 Mendel’s Second Law

The Law of Independent

Assortment

“Members of different pairs of

alleles assort independently into
gametes”
Multi-Loci Crosses
1) Mendel’s Second Law
– Independent Assortment
2) the dihybrid cross
3) the trihybrid cross
4) a general model
 dissecting a
dihybrid cross P

F1 or F1 F1 F1


self F2 or intercross F2 F2
dihybrid cross
 parental recombinant
gametes gametes

{
{
parental
gametes
{
recombinant
gametes
{
 gametic array

RY Ry rY ry

RY
gametic array

zygotic array
Ry

rY

ry
 P RRYY  rryy

F1 RrYy

F2
1RRYY:2RRYy:1RRyy
Geno Seg
2RrYY:4RrYy:2Rryy
1rrYY:2rrYy:1rryy
• two single-gene traits Pheno
• complete dominance
at both loci 9:3:3:1 Seg
 gametic array

RY Ry rY ry

RY RRYY RRYy RrYY RrYy

gametic array

zygotic array
Ry RRYy RRyy RrYy Rryy

rY RrYY RrYy rrYY rrYy

ry RrYy Rryy rrYy rryy

Punnett Square
 true breeding F2 genotypes

RY Ry rY ry

RY RRYY RRYy RrYY RrYy

Ry RRYy RRyy RrYy Rryy

rY RrYY RrYy rrYY rrYy

ry RrYy Rryy rrYy rryy

 dihybrid F2 genotypes

RY Ry rY ry

RY RRYY RRYy RrYY RrYy

Ry RRYy RRyy RrYy Rryy

rY RrYY RrYy rrYY rrYy

ry RrYy Rryy rrYy rryy

monohybrid F2 genotypes
 independent assortment
two characters – complete dominance
ratio genotype phenotype genotype breeding
1 RRYY R–Y– parental true breeding
2 RRYy R–Y– recombinant seg 3:1 at Y
1 RRyy R–yy recombinant true breeding
2 RrYY R–Y– recombinant seg 3:1 at R
4 RrYy R–Y– recombinant seg 9:3:3:1
2 Rryy R–yy recombinant seg 3:1 at R
1 rrYY rrY– recombinant true breeding
2 rrYy rrY– recombinant seg 3:1 at Y
1 rryy rryy parental true breeding
16 9 4 2 parental t.b vs seg.
 independent assortment
two characters – complete dominance

ratio geno pheno

9 R–Y– round,
yellow
3 R–yy round,
green
3 rrY– wrinkled,
yellow
1 rryy wrinkled,
green
branch diagram – phenotypic segregation
 Mendel’s
First Law of
Segregation
(twice)
 Mendel’s Second Law
Independent Assortment
 Mendel’s Second Law
the dihybrid cross
mathematically
F1 gametes 1RY : 1Ry : 1rY :1ry
F2 geno seg (1RY : 1Ry : 1rY : ry)2
= (1RY : 1Ry : 1rY : ry)  (1RY : 1Ry : 1rY : ry)
= 1 RRYY : 2 RRYy : 1 RRyy
2 RrYY : 4 RrYy : 2 Rryy
1 rrYY : 2 rrYy : 1 rryy
F2 pheno seg = 9 R-Y- : 3 R-yy : 3 rrY- : 1rryy
Now let’s consider a cross that produces a
trihybrid
*

?
* note that there are other parental combinations
to produce such a trihybrid, e.g., AAbbCCaaBBcc
 consider three pairs
of homologous chromosomes (no COs)
(Fig. 2.17)

m = maternal
p = paternal
23 = 8 orientations
(incl. mirror images)
at MEI I)
23 = 8 different
gametes after MEI II
let's put genes on these chromosomes
genotype: ABC/abc

A
BC
a
c b
ABC ABC
abc
ABc
abc abC
Abc
ABC aBC
ABc
easier AbC AbC
to account Abc
for gametes aBC aBc
this way aBc
(nesting) abC
abc 23 = 8 gametes
accounting for all gametes

A BC
A Bc
A bC
A bc
a BC
a Bc
a bC
a bc
Here we have nested C/c
within B/b within A/a
3 locus F2 segregation

an 88 Punnett Square

(64 cells)
27 different genotypes

genotypic segregation
1:2:1:2:4:2:…
phenotypic segregation
depends
on gene action
 a general model
as stated by Mendel
and incorporating
both the 1st & 2nd Laws
• if a genotype is heterozygous at n loci…
• it will produce 2n different gametes…
• and upon ing it will produce 3n different
progeny genotypes in the F2 generation…
• with a “smallest perfect population”
including 4n individuals…
• …and so welcome to the “numbers
game” that is genetics, combinatorics,
and animal and plant breeding…
• 5. If you had a fruit fly that was of
phenotype A, what test would you make to
determine whether it was AA or Aa.?
• 6. Two black pigs were mated and over
several years produced 29 black and 9
white offspring. Explain these results
giving the genotypes of parents and
progeny.
8. A tall pea plant producing green round
seed is crossed with a dwarf plant having
green rounds. The progenies from this
cross are as follows:
tall green round : 3,
dwarf green round : 3,
tall green wrinkled : 1
dwarf green wrinkled :1
Determine the genotypes of the two plants..
 probability
and hypothesis testing
in genetics…
 THE MULTIPLICATION RULE
for calculating the probability
of two or more “concurrent” or
“sequential” events
• used in “and” situations
• a very simple example: A couple will produce
two children over time
• Q: what is the probability of having
two girls (XX and XX)?
• A: Prob (girl)  Prob (girl)
= Prob (XX)  Prob (XX)
= 0.5  0.5 = 0.25
 THE MULTIPLICATION RULE
(Mendel’s 2nd Law; Independent Assortment)

Q: What is the probability of a wrinkled,

yellow seed produced in the F2 progeny of
an F1 RrYy self-pollination?
A: ¼  ¾ = 3/16.
 THE ADDITION RULE
for calculating the probability
of two or more mutually exclusive events

• used in “either/or” situations

• a very simple example: A couple is expecting
a child.
• Q: what is the probability of having
a girl (XX) or a boy (XY)?
• A: Prob (girl or boy)
= Prob (XX) + Prob (XY)
= 0.5 + 0.5 = 1
 the COMPLEMENT (or"not“) RULE
often we can use a shortcut to
calculating the probability of a
particular event occurring
at least once
for example: what is the probability of at least one
A1A1 zygote among 12 zygotes produced by a A1A2 
A1A2 mating? [apply Mendel's 1st Law]
start by calculating Prob (no A1A1 among 12 zygotes)
= (.75)12 = .03167635
answer: Prob = 1-(.75)12 = .96832365
 probability rules
1) MULTIPLICATION RULE
- used in "and" situations
- a product of probabilities
of independent events
2) ADDITION RULE
- used in “either/or” situations
- a sum of alternative probabilities
3) COMPLEMENT RULE (OR “NOT” RULE)
- subtraction from 1, after determining
the probability of an alternative
that is easy to calculate
- useful for calculating the probability
of an event occurring at least once
binomial distribution probability-For two
mutually exclusive events and n trials
• Binomial expansion: The set of terms along
with their coefficients obtained by expanding
the general term (a+b)n
• (a+b) n = an+an-1b+an-2b2+…..+bn
coefficient of preceding term ×
Coefficient = exponent of preceding term
of next term Ordinal number of preceding
term
binomial distribution
probability

n!
P
s t
a b
s! t!
 n!
P 
s t
a b
s! t!
recall:
! = factorial
e.g., 3! = 1•2•3 = 6
and 0! = 1
0
and x = 1
 n!
P
s t
a b
s! t !
where P = overall probability of two independent
events
w/ event X with probability a occurring s times
& event Y with probability b occurring t times
also a + b = 1
n = s + t (total occurrences of X & Y)
 n!
P
s t
a b
s! t !
Lee & Georgie Casey’s children (Pat & her siblings)
What is the probability of 5 girls & 4 boys?

s = event X (XX♀) = 5; t = event Y (XY♂) = 4

n=s+t=9
a = 0.5 ; b = 0.5
9!
P
5 4
0 .5 0 .5
5!4!
 n!
P
s t
a b
s! t !

362880
P  0 . 03125  0 . 0625
120  24

= .246094
 n!
P
s t
a b
s! t !
What is the probability of 9 girls among 9 children?

s = event X (XX♀) = 9; t = event Y (XY♂) = 0

a = 0.5 ; b = 0.5

9!
P 
9 0
0 .5 0 .5
9!0!
 n!
P
s t
a b
s! t !

362880
P  0 . 001953  1
362880  1

= .001953
 what about this particular order?
Kids Mike Pat Pam Mark Tierney Kate Peggy Matt Jim

♂or♀ ♂ ♀ ♀ ♂ ♀ ♀ ♀ ♂ ♂

prob 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5

9
1 1
P  
2 512
P= (0.5)9 = 0.001953
an example of the multiplication rule
of joint probability
of independent events
 another example
of the multiplication rule
of joint probability of independent events

1 1 1
Pr ob ( Pat 1stGirl )   
512 5 2560
= 0.000391

the use of branch diagrams to calculate the

expected frequency of particular genotypes
and phenotypes is an important example of
using the multiplication rule, & so are Punnett
s
 hypothesis testing
chi-square goodness-
of-fit-test
( obs  exp )
2

 2
df
  exp
df = # of degrees of freedom
(generally equal to 1 less than
the number of classes, n-1)
obs = # of observed events
exp = # of expected events
Principle of Particulate Inheritance

Rr

7324
{ ____

____
3R–:1rr

Principle of Dominance
Father Mendel’s peas (round & wrinkled)
What is the X2 probability
of 5474 round & 1850 wrinkled peas in the F2?

null hypothesis: round & wrinkled are produced

in a 3:1 ratio in the F2
Father Mendel’s hypothesis
as a Punnett square
 Father Mendel’s peas (round & wrinkled)
What is the X2 probability
of 5474 round & 1850 wrinkled (total = 7324 peas)
in the F2?
null hypothesis: round & wrinkled are produced
in a 3:1 ratio in the F2
according to our single locus, complete dominance model
expected round = ¾ • 7324 = 5493
expected wrinkled = ¼ • 7324 = 1831

round wrinkled
( 5474  5493 ) (1850  1831 )
2 2

2    0 . 0657  0 . 1972  0 . 2629

1df 5493 1831
 chi-square probability

with a table: the “old-fashioned way”

 X2 prob for Mendel’s peas

P<0.9 Prob<90% we accept the null hypothesis

 Professor Groose’s peas
(purple & white flowers)
What is the X2 probability
of 901 purple-flowered & 650 white-flowered
(1551 total) pea plants in the F2?
null hypothesis: purple & white plants are produced
in a 3:1 ratio in the F2 (1 locus, complete dominance)

according to our single locus, complete dominance model

expected purple = ¾ • 1551 = 1163.25
expected white = ¼ • 1551 = 387.75

purple white
( 901  1163 . 25 ) ( 650  387 . 75 )
2 2

2    59 . 12  177 . 37  236 . 49
1df 1163 . 25 387 . 75
P PP  pp
purple white

F1 Pp purple

F2 1PP:2Pp:1pp
purple 3P–:1pp white
 X2 prob for Groose’s peas

P<0.005 P<0.5% Groose rejects the null hyp.

 using Excel to calculate
the chi-square probability
# obs exp X2
p u rp le 901 1 1 6 3 .2 5 5 9 .1 2 3 2
w h ite 650 3 8 7 .7 5 1 7 7 .3 6 9 6
df X 2 p ro b
sum : 1551 1551 2 3 6 .4 9 2 8 1 2 .2 9 E -5 3

2
X 1df prob = 2.29*10-53

thus, Groose rejects the null hypothesis at the

P = 0.0000000000000000000000000000000000000000000000000000229
probability level
 Is there a reasonable
alternative hypothesis?

• Dr Groose thinks so
• but that’s getting ahead of our story
• soon we’ll encounter something
called “epistasis”
• to be continued…
Sex Determination
& Sex-Linked
Characteristics
 what is life?
 sometimes
it takes two


 
 The Strange sex
chromosome
Case karyotype
of Platypus Sex

5X+5Y 
5X+5X 
Ordinarily, animals produce
1♂:1♀
sex ratios

→
 Even if there is an excess of one sex
(for whatever reason) in one generation
expect 1♂:1♀ in the next generation.
 Sex Determination
the typical eukaryotic life cycle
an alternation of generations

the the
“hard part” “easy part”
of sex of sex
 angiosperm
plant life cycle

hermaphroditic
(here)
or
monoecious
or
dioecious
Homo sapiens life cycle: dioecious

XY XX
human sex chromosomes

X Y
sperm = male gamete
“smallest human cell”

egg = female gamete

“largest human cell”
 male diploids (2n)
produce haploid sperm (n)

female diploids (2n)

produce haploid eggs (n)
 telomeres

autosome
= nonsex chromosome
(not these, all the rest)
sex chromosome
= X or Y; W or Z; etc.

telomeres
(Y too)
Human males are hemizygous
for loci on the X chromosome (e.g., A or a)
 Homo sapiens
22 pairs of autosomes
1 pair of sex chromosomes
Sex determination systems (animals)
1. Environmental eg. Bonelia
 Free living larva- develops into female
 Larva attached to the proboscis if female worm-develops into
male

2. Chromosomal:
 XXXO where XX = & XO = grasshoppers
 XXXO where XX = & XO = fumea
 XXXY where XX = & XY = mammals
 ZZZW where ZZ = & ZW = birds
homogametic sex   heterogametic sex
 n2n where 2n = & n = social insects (honey bee, ants)

3. genic system (autosomes) Drosophila

 X:A ratio = 1.0 = & 0.5 =
metafemales, metamales,
& intersex individuals also possible
 haplodiploidy
queen drone

as larva
drone worker
 Homo sapiens
the Y chromosome

SRY gene, found

~80 genes, only on the Y chrom
60 unique, causes development
expressed of male characters
in testes; regulating genes
♂v.♀ diff. throughout the
~0.2% genome
 karyotype
nondisjunction (genotype) phenotype
at meiosis
XO
Turner
Syndrome

XXY
Kleinfelter
Syndrome
Sex determination systems (plants)
1. Environmental eg. Melon, cucumber,
cannabis
2. Monogenic eg. Papaya, asparagus, spinach
3. Chromosomal
 XXXO where XX = & XO = Dioscorea
 XXXY where XX = & XY = Cannabis
 XXXY1Y2 where XX = & XY1Y2 = Rumex,
Humulux
 ZZZW where ZZ = & ZW = Fragraris
 SexLinked Characteristics

We’ll consider:
1) Drosophila: Thomas Hunt Morgen’s
classic experiment that demonstrated
sexlinkage, demonstrated that males
are HEMIZYGOUS at loci on the X
chromosome and confirmed
The Chromosome Theory of Inheritance,
2) Drosophila: Calvin Bridges’ use of
NONDISJUNCTION to further confirm
The Chromosome Theory of Inheritance,
and
3) Homo sapiens: See why more men than
women are color blind
 model #4
•Drosophila
melanogaster
•the fly
•14000
genes
+ = red w = white
wildtype mutant
dominant recessive
♀
♂
Cytological examination of flies
confirmed the conclusion
of sex-linkage of the w locus.
nondisjunction – more proof of sexlinkage
 why are more men than women colorblind?
Normal color blind Reciprocal cross

+ = normal
vision
c=
colorblind
How important is sex?
• genetic recombination
- meiosis and evolution
• sex affects gene expression
throughout the genome
- on both autosomes
& sex chromosomes
• some genes are sexlinked
e.g., humans: ~24000 loci & 2n=46
so ~1000 loci on the X (~4.3%)
 Extensions
& Modifications
of Basic Principles
(gene interactions)
Cuénot’s Odd Yellow Mice
1:2:1 geno seg  2:1 pheno seg
 Dominance
Revisited
Gene Action
intralocus gene interaction
or
interallelic gene interaction
 A1A1>A1A2>A2A2
additivity: A1A1=2A1A2; A2A2=0A1A1
complete
dominance

includes
additivity

may include
overdominance
 RR = Rr > rr
complete
dominance

PP > Pp > pp
includes
additivity Pp=1/2PP and pp=0PP

may include A1A1 < A1A2 > A2A2

overdominance
 biochemical genetics
of complete dominance
phenotype

metabolism

genotype
 phenotype trait A expressed
folding & function
protein-A proteinA

translation
mRNAA mRNAA

transcription
AA genotype
replication
AA
 phenotype trait A expressed
folding & function 
proteinA proteina

translation 
mRNAA mRNAa

transcription 
Aa genotype
replication
Aa
phenotype trait A not expressed

folding & function 
protein-a proteina

translation 
mRNAa mRNAa

transcription 
aa genotype
replication
aa
Gene Action at a Single Locus
• complete dominance
RR = Rr > rr
• incomplete dominance
PP > Pp > pp
• additivity
Pp=1/2PP and pp=0PP
• overdominance (heterosis)
A 1A 1 < A 1A 2 > A 2A 2
• codominance
A1A2 expresses
both A1 and A2 phenotypes
codominance: ABO blood types and
possible transfusions
codominance: in terms of the I locus, you
are more closely related to some chimps than
to other humans!
 Gene Interaction or Epistasis
until now, we’ve been concerned with
how an individual locus and
interallelic interactions
(intralocus interactions)
at that locus affect a trait
from now on, we’re concerned with how
multiple loci and
interlocus interactions
among those loci affect a trait
taking into account the
interallelic interactions
(intralocus interactions)
at each of those loci
Epistasis or not?
 But first, two loci,
no epistasis

two loci independently

affecting a "single trait"
Bell Pepper pigmentation
 bell pepper genetics
R– = red pigment
rr = no red pigment
C– = chlorophyll decomp.
cc = no chlorophyll decomp.

Epistasis?
No, not really.
genotypic segregation:
1:2:1:2:4:2:1:2:1
phenotypic segregation:
9 red : 3 brown : 3 yellow : 1 green
cultivars: RRCC none rrCC rrcc

bad looking but good for you?

& what about orange peppers?

 P rrcc  RRCC
green red

F1 RrCc red

1RRCC:2RRCc:1RRcc
F2 2RrCC:4RrCc:2Rrcc
1rrCC:2rrCc:1rrcc
What is the phenotypic segregation?
 gametic array

RC Rc rC rc

RC RRCC RRCc RrCC RrCc

gametic array

zygotic array
Rc RRCc RRcc RrCc Rrcc

rC RrCC RrCc rrCC rrCc

rc RrCc Rrcc rrCc rrcc

Punnett Square
 gametic array

RC Rc rC rc
RRCC RRCc RrCC RrCc
RC
gametic array

red red red red

zygotic array
RRCc RRcc RrCc Rrcc
Rc red brown red brown
RrCC RrCc rrCC rrCc
rC red red yellow yellow
RrCc Rrcc rrCc rrcc
rc yellow green
red brown

from genotype to phenotype

 bell pepper genetics summary
• not truly epistasis (no interlocus
interaction)
• the loci that condition red pigment
production (R locus) and chlorophyll
decomposition (C locus) operate
independently of one another…
• …despite the fact that together they affect
pepper pigmentation
• the 9:3:3:1 F2 segregation is the same as
for two separate traits in the F2 from the
dihybrid cross in pea involving the R
locus (round vs wrinkled seed) and the Y
locus (yellow vs green cotyledons)
Epistasis or not?

Fruit color
in peppers
recessive epistasis

in Labs
 Labrador Retriever Genetics
B– = black pigment E– = dark pigment
bb = brown pigment ee = no dark pigment

BbEe  BbEe
black lab black lab

?
The Punnett Square (next slide) may be
considered to be an “intercross F2”, and would
involve many litters of puppies produced by
numerous matings of dihybrid black labs
 gametic array

BE Be bE be

BE BBEE BBEe BbEE BbEe

gametic array

zygotic array
Be BBEe BBee BbEe Bbee

bE BbEE BbEe bbEE bbEe

be BbEe Bbee bbEe bbee

Punnett Square
 gametic array

BE Be bE be
BBEE BBEe BbEE BbEe
BE
gametic array

black black black black

zygotic array
BBEe BBee BbEe Bbee
Be black yellow black yellow
BbEE BbEe bbEE bbEe
bE black black brown brown
BbEe Bbee bbEe bbee
be brown yellow
black yellow

from genotype to phenotype

 Labrador Retriever Genetics
B– = black pigment E– = dark pigment
bb = brown pigment ee = no dark pigment

This is RECESSIVE EPISTASIS

Here there is true
INTERLOCUS INTERACTION
Here we can say that the ee genotype
is epistatic to the B locus
Or we can say that the B locus
is hypostatic to the ee genotype
Epistasis or not?

Fruit color
in peppers
 Summer Squash Pigment Genetics
W– = no pigment Y– = yellow
ww = pigment yy = green

WWYY  wwyy
white green

WwYy white
intercross
F2
 gametic array

WY Wy wY wy
WWYY WWYy WwYY WwYy
WY
gametic array

white white white white

zygotic array
WWYy WWyy WwYy Wwyy
Wy white white white white
WwYY WwYy wwYY wwYy
wY white white yellow yellow
WwYy Wwyy wwYy wwyy
wy yellow green
white white
from genotype to phenotype
Summer Squash Pigment Genetics
W– = no pigment Y– = yellow
ww = pigment yy = green

This is DOMINANT EPISTASIS

Here there is true
INTERLOCUS INTERACTION
Here we can say that the W allele
genotype is epistatic to the Y locus
Or we can say that the Y locus
is hypostatic to the W allele
Epistasis or not?

Fruit color
in peppers
 Gene Interaction

interlocus gene interaction

i.e., more than one locus

and the interaction
among alleles at those loci
affecting the same trait
 EPISTASIS
(duplicate recessive)
together with
Mendel’s Second Law
The Law
of Independent
Assortment
 1 2 3
precursor intermediate product
colorless colorless color
(substrate) (substrate)

2º metabolites

e.g., petunia

metabolic pathway
 1 2 3
precursor intermediate product
colorless colorless color

enzyme A enzyme B
folding & function

translation

transcription

replication 2 loci: A and B

 1 2 3
precursor intermediate product
colorless colorless color

enzyme A enzyme B

A– B–
 1
precursor
colorless

X ?
enzyme B

aa ––
 1 2?
precursor intermediate
colorless colorless

?
enzyme A X

–– bb
 1
precursor
colorless

X X

aa bb
 P AABB  aabb
red white

F1 AaBb red

1AABB:2AABb:1AAbb
F2 2AaBB:4AaBb:2Aabb
1aaBB:2aaBb:1aabb
• one trait, two loci
• complete dominance 9 red : 7 white
at both loci, duplicate recessive epistasis
 gametic array

AB Ab aB ab

AB AABB AABb AaBB AaBb

gametic array

zygotic array
Ab AABb AAbb AaBb Aabb

aB AaBB AaBb aaBB aaBb

ab AaBb Aabb aaBb aabb

Punnett Square
 gametic array

AB Ab aB ab

AB
gametic array

zygotic array
Ab

aB

ab

Petunia Square
Epistasis or not?

Fruit color
in peppers

Flower color
in petunias

petunias petunias

petunias petunias
Epistasis or not?

Fruit color
in peppers

Flower color
in petunias

dominance
} Polygenic
traits
 Duplicate Dominance

• as above except dominance gene

action at each of two loci (e.g., A and B)
and, again, no epistasis
 Again, two loci,
no epistasis
two loci independently
and quantitatively
affecting a single trait

typically, polygenic traits

 Duplicate Dominance

P AAbb  aaBB
2 units 2 units

F1 AaBb 4 units
“hybrid vigor”
 Model
A– = 2 units

F2 ? aa = 0 units
B– = 2 units
bb = 0 units
 DUPLICATE DOMINANCE
ratio genotype phenotype genotype breeding
1 AABB 4 units recomb TB 4 units
2 AABb 4 units recomb seg 3:1 [4:2]
1 AAbb 2 units parental TB 2 units
2 AaBB 4 units recomb seg 3:1 [4:2]
4 AaBb 4 units recomb seg 9:6:1 [4:2:1]
2 Aabb 2 units recomb seg 3:1 [2:0]
1 aaBB 2 units parental TB 2 units
2 aaBb 2 units recomb seg 3:1 [2:0]
1 aabb 0 units recomb TB 0 units
16 9 3 2 parental t.b vs seg.
overall F2 segregation
9 4 units : 6 2 units : 1 0 units
note the “transgressive segregates” &… the best
Epistasis or not?

Fruit color
in peppers

Flower color
in petunias

dominance
} Polygenic
traits
Allopolyploids

(or AaBb )
 Epistasis (YES) or not (NO)?
?
N*
Fruit color
'' in peppers

Y
Y
Y
Flower color
'' in petunias

N** dominance
} Polygenic
traits

Y Allopolyploids

Y We’ll skip

N* = separate traits N** = cumulative effects

 And all of these all of these
dihybrid phenotypic ratios,
involving separate traits,
or epistasis of many kinds,
or cumulative effects…
…are underlain
by a genotypic ratio of
1:2:1:2:4:2:1:2:1
(as per Mendel’s Second Law)
 ratios, ratios, ratios

1:1
3:1

1:4:6:4:1
Mendel’s Success – Seven Traits

• pleiotropy: one gene affecting

more
pea than one trait,
(Pisum like seed
sativum L.)
color & flower color in pea
 Linkage,
Recombination
& Eukaryotic
Gene Mapping
(breaking Mendel’s 2nd Law)
 Alfred Sturtevant
and the First Genetic Map
linkage: linked
genes may be
inherited together
for generations
 What we’re gonna do
• we will differentiate between
- interchromosomal recombination
among genes on different chromosomes
- intrachromosomal recombination
due to crossing over between loci
on the same chromosome
• we will differentiate between
- physical linkage (loci on same chromosome,
same DNA molecule)
- genetic linkage (loci on same chromosome,
same DNA molecule, AND so close
together that recombination is <50%
• we will differentiate between
- coupling phase (cis) linkage
- repulsion phase (trans) linkage
• And, we will map genes
 Why is linkage important?
• on average, any two loci in the eukaryotic genome
are not linked (e.g., Probability of physical linkage
for two random human loci  1/23 = 4.35%)
• thus, alleles at most pairs of loci will freely
recombine in meiosis according to Mendel’s 2nd
Law of Independent Assortment
• BUT, at the same time, every locus in the genome
is physically (and often genetically) linked to other
loci on the same chromosome
• thus, crossing-over at meiosis is essential
to recombination between linked loci
• so… we will differentiate between
- interchromosomal recombination &
- intrachromosomal recombination - requires CO
• and we will map genes
Recombination is the sorting of
alleles into new combinations

And it all happens in meiosis…

interchromosomal
recombination

1:2:1:2:4:2:1:2:1
 crossing over
&
intrachromosomal
recombination
illustrated here
 nature breaks

Mendel’s Second Law

when loci
are genetically linked
 genetic model

Bateson, Saunders
& Punnett, 1905
 obs exp (o-e)2/e
Purple 284 9/16*381 22.66
Long = 214.31
Purple 21 3/16*381 35.61
Round = 71.44
Red 21 3/16*381 35.61
Long = 71.44
Red 55 1/16*381 40.86
Round = 23.81
total 381 381 102.75
P < .005
 2  102 . 75 
3 df P = 3.9810-32
 Is purple:red
segregation 3:1?
obs exp (o-e)2/e
Purple 305 3/4*381 1.30
= 285.75
Red 76 1/4*381 3.89
= 95.25
total 381 381 5.19

P < .05 uh oh!

 2  5 . 19 
1df P = .022754
 Is long:round
segregation 3:1?
obs exp (o-e)2/e
Long 305 3/4*381 1.30
= 285.75
Round 76 1/4*381 3.89
= 95.25
total 381 381 5.19

P < .05 uh oh!

 2  5 . 19 
1df P = .022754
 testing for segregation
&
independent assortment
using the Χ2 goodness-of-fit test
1) test single-locus ratio separately (locus A)
2) test single-locus ratio separately (locus B)
3) test joint-loci assortment together
(loci A&B)
(in general, we’ll use these simplifying rules
and ignore Contingency Tests for now)
Consider a hypothetical case
of linkage
P AABB  aabb
AB ab
 
  
AB ab

AB 
F1 ab



 AB
F1 

ab

AB

AB
meiosis ab

ab

now what?
 CO Prometaphase I NCO
(meiosis I)

crossover noncrossover
 Meiosis I

CO Meiosis II NCO
AB AB
 
Ab AB 

aB ab
 
ab ab
 
10% 90%
 Parental AB = 0.475
Recombinant Ab = 0.025
Recombinant aB = 0.025
Parental ab = 0.475

AB .10*1/4 AB .90*1/4  = 1.000

= 0.025 = 0.225
Ab .10*1/4 AB .90*1/4
= 0.025 = 0.225
aB .10*1/4 ab .90*1/4
= 0.025 = 0.225
ab .10*1/4 ab .90*1/4
= 0.025 = 0.225
Genetic Segregation  = 1.000

♂ .475 .025 .025 .475

♀ AB
.22563
Ab
.01189
aB
.01189
ab
.22563
.475AB
AABB AABb AaBB AaBb
.01189 .00063 .00063 .01189
.025 Ab
AABb AAbb AaBb Aabb
.01189 .00063 .00063 .01189
.025 aB AaBB AaBb aaBB aaBb
.22563 .01189 .01189 .22563
.475ab
AaBb Aabb aaBb aabb
 = 1.000 not 1:2:1:2:4:2:1:2:1  = 1.000
 What it is:
AABB AABb Aabb AaBB AaBb Aabb aaBB aaBb aabb
.2256 .0238 .0006 .0238 .4639 .0238 .0006 .0238 .2256

Compared to no linkage:
AABB AABb Aabb AaBB AaBb Aabb aaBB aaBb aabb
.0625 .1250 .0625 .1250 .2500 .1250 .0625 .1250 .0625
1 2 1 2 4 2 1 2 1
 Phenotypic Segregation
…assuming a 9:3:3:1 segregation
for two single gene traits
w/ complete dominance @ both loci
and no genetic linkage
pheno w/link wo/link 
AB 0.72571 0.5625 = 9/16 Parental
Abb 0.02441 0.1875 = 3/16 Recombinant
aaB 0.02441 0.1875 = 3/16 Recombinant
aabb 0.22563 0.0625 = 1/16 Parental

=1 =1
 (between A and B loci)

when no cross-over occurs between A and B loci,

products of meiosis are 100% Nonrecombinant

(between A and B loci)

when a single cross-over occurs between A and B loci,

products of meiosis are 50% Recombinant & 50% Nonrecombinant

thus, overall, genetic linkage results

in <50% recombinant chromosomes
testcross:
Linkage complete no
& linkage linkage
Recombination
Between
Two Genes
(the extremes)

Meioses with
and without
crossing over
together
result in
LESS than 50%
recombination
on average
“less” NOT “more” 
testcross:
Linkage complete no
& linkage linkage
Recombination
Between
Two Genes
(the extremes)

Meioses with
and without
crossing over
together
result in
LESS than 50%
?
recombination
on average
testcross
 an example
where a CO occurs
32% of the time
between two loci
i/t dyhybrid parent
to produce:
16% recombinant gametes
8% Td ; 8% tD
84% parental gametes
42% TD ; 42% td
sampling
gametes
produced
by the
dihybrid
parent
 …thus, in the
testcross,
progeny are
produced at the
same
frequencies as
production of
gametes
produced by the
dihybrid parent
…and, thus,
the TC is the
most efficient
gene mapping
procedure
AABB  aabb

AaBb

Dihybrid
gametes

.25 AB
.25 ab
.25 Ab
.25 aB
.50 AB
.50 ab
>.25 AB
>.25 ab
<.25 Ab
<.25 aB
Barbara McClintock and Harriet Creighton

demonstrated that genetic recombination

is the result of physical crossing over
 simplified!

almost a testcross

Recombinant,
Physically &
Genetically

e.g., NCOs
 And now we shall
“work backwards”
• Which is mostly what geneticists do
• After all, we do not have prior
knowledge of linkage relationships
(but now sometimes we do with
genomics – physical linkage)
• Rather, we mostly infer linkage by
analyzing segregation data
• …as follows…
• …and first, an equation…
 calculating
recombination frequency
from a testcross

recombinant # recombinant progeny

frequency =  100%
total # progeny
e.g., calculating the recombination
frequency from a testcross
recombinant
frequency =

# recombinant progeny
total # progeny
100%

8+7
=
55 + 53 + 8+ 7
 100%

= 11.9%
(23.8% C.O.)
map units
recombinant
frequency = 11.9%
1% recombination
= 1 map unit = 1 m.u.
= 1 centiMorgans = 1 cM

so here, in tomato,
the M and D loci
lie 11.9 m.u. apart
on the same chromosome
all examples so far,
cis arrangement,
coupling phase
linkage
the Australian blowfly
cis trans
either cis or trans, the calculation is
essentially the same: the rarest
classes go in the numerator
recombinant
frequency =
# recombinant progeny
100%
total # progeny
10 + 10
=  100%
40 + 40 + 10 + 10

= 20% (40% C.O.)

so, the p and b loci
lie 20 m.u. apart
And remember!
recomb freq ≤ 50%
gene mapping with
recombination
frequencies

A to B = 5 m.u.
B to C = 10 m.u.
A to C = 15 m.u.
 A to B = 5 m.u.
B to C = 10 m.u.
A to C = 15 m.u.
B must be between A & C
A B C

5 m.u. 10 m.u.

15 m.u.
 D is closest to A (of A,B,&C)
D is farthest from C (of A,B,&C)
D

8 m.u.
 more info
E to D, 50% recomb
E to B = 40 m.u.
E to F = 35 m.u.
F to D = 18 m.u.
G to D, 50% recomb
G to E = 20 m.u.
18 m.u. F 35 m.u. E G
40 m.u. 20 m.u.

73 m.u.
…with time & effort, genetic maps
grow, and gaps are filled in
 another example: LMNOP
L-M 3 what loci are farthest apart?
L-N 9 L 14 O
L-O 14
L-P 6
what loci are closest to them?
M-N 6 L 3 M 6 N 5 O
M-O 11
M-P 3
N-O 5 what’s left?
N-P 3 L 3 M 3 P 3 N 5 O
O-P 8
does it all add up? Yes. Done!
 What about
Double Crossovers?

Late Prophase of Meiosis I

2-strand DCO

2-chromatids
DCO
1 red, 1 blue
cancels
recombination
between A & B loci
AB
all nonrecombinant AB
(all parental) ab
ab
t 3-strand Ab
h AB
e DCO aB
2 red, 1 blue ab
o
t 3-strand AB
h Ab
e DCO ab
r 1 red, 2 blue aB

D Ab
C 4-strand Ab
O DCO aB
s 2 red, 2 blue aB
 The 4 DCOs in the previous two
slides account for all possible DCOs
and occur with equal frequency, and
overall, result in equal production of
AB, Ab, aB, ab
gametes
i.e., free (50%) recombination
(prove it to yourself if you want to;
it only takes about an hour to do)
Linkage & Recombination
Among Three Genes
3-point cross

the rarest recombinants

are those with
only the middle gene altered
 interference
coefficient of # observed DCOs
coincidence = # expected DCOs

for QRS,
where Q-R CO freq = 0.250 (recomb. freq. = 0.125),
and R-S CO freq = 0.100 (recomb. freq. = 0.050),
we expect DCO freq = 0.250*0.100 = 0.025
but we observe DCO freq = 0.015
so, C = 0.015/0.025 = 0.600
 interference
coefficient of # observed DCOs
coincidence = # expected DCOs

interference = I = 1 - C

for QRS,
I = 1 - 0.600 = 0.400
genetic and physical map distances
are related in complex ways
 “mapping functions” relate
recombination frequency to actual
physical distance between genes

Note: at 50 m.u.  30% recombination

at 150 m.u.  50% recombination
 a genetic
map in
Drosophila
4 chromosomes
=
4 linkage groups
Genetic Distance (cM)
Human Chromosome 1

400

250 ave.

100

0
0 50 100 150 200 250
Physical Distance (Mb)
(Wellcome Trust, 2006)

250 Mbp in length (8% of 3.2 Bbp)

250 cM in length
So, 1cM/1Mbp (1cM = 1 million base pairs)
3,141 genes (12.5% of 25,000 genes)
Also, 3141 genes/250 Mbp = 12.6 genes per Mbp
>350 genetic disease loci
Mapping Human Genes
via Pedigree Analysis
 Ultra-Modern
Chromosome Mapping
• via Molecular Markers
• via Genomewide Association
Studies
• via Whole-Genome Sequencing
- Chapters 19 and 20 -
 Physical Chromosome
Mapping
• via Deletion Mapping
• via Somatic Hybridization
• via In Situ Hybridization
 Deletion Mapping

locus A locus A
within deletion outside deletion
Somatic-Cell
Hybridization

different human
chromosomes
lost in different
cell lines
Somatic-Cell Hybridization
Results

the gene must be

on chromosome 4
Somatic-Cell Hybridization
& Chromosome Deletions
in situ hybridization
let’s go FISHing!

let’s go sequencing!
recall this figure
from Chap.2,
summarizing
MEIOSIS

as drawn,
it also illustrates
INTERCHROMOSOMAL
RECOMBINATION
 this
orientation
at MEI I
results
in all
recombinant
products

thus, 50% overall

INTERCHROMOSOMAL
but this RECOMBINATION
equally
likely
orientation
results in all
parental
products
recall this figure
from the
beginning of
this chapter
crossing over
&
intrachromosomal
recombination
illustrated here
 Meiosis I Meiosis II
as illustrated in Fig. 7.3 P
(INTRACHROMOSOMAL R
RECOMBINATION) O
D
but half of meioses will also U
recombine centromeres C
(INTERCHROMOSOMAL T
RECOMBINATION) S
Meiosis I Meiosis II
compare
& contrast
 Summary
• we have differentiated between
- interchromosomal recombination
among genes on different chromosomes
- intrachromosomal recombination
due to crossing over between loci
on the same chromosome
• we have distinguished
- physical linkage (loci on same chromosome,
same DNA molecule)
- genetic linkage (loci on same chromosome,
same DNA molecule, AND so close
together that recombination is <50%
• we have defined
- coupling phase (cis) linkage
- repulsion phase (trans) linkage
• And, we mapped genes
 Gene Action Models
for Heterosis (Hybrid Vigor)
at a single locus
• overdominance A1A1 < A1A2 > A2A2
involving multiple loci
• complementation (DUP REC EPI)
AAbb  aaBB  AaBb
• duplicate dominance (NO EPI)
AAbb  aaBB  AaBb
• pseudo-overdominance
tight repulsion phase (trans)
linkage of dominant alleles
(with epistasis or not)
Extranuclear
inheritance
(Organelle DNA)
uniparental inheritance – maternal inheritance
mitochondrial DNA – mtDNA
1)a relatively short molecule
 2)many copies per cell
3)evolves rapidly
4)no meiosis
 5)clonal inheritance


chloroplast DNA – cpDNA

characteristics similar

to mtDNA

♀   
 The Donkey:
A Wild Ass or a Half Ass?

kiang – a half ass

donkey – an ass
evolutionary
tree 
of Equus

based 
on variation
in a 479bp
mtDNA
sequence

two separate
domestication
events within
the wild asses
 The Biology of Mitochondria
and Chloroplasts

individual eukaryotic cells may carry

from dozens to hundreds of organelles,
each with many copies of the organellar genome
 The Biology of Mitochondria
and Chloroplasts

the mitochondrion and the chloroplast

each carry genes for some of their protein
constituents especially for membrane functions
like electron transport
and photosystems II and I; & RuBisCo
new organelles arise by
binary division
of existing organelles
within the eukaryotic cell
 homoplasmy, heteroplasmy
& replicative segregation
(from lower left)
normal   mutant

expect somatic cell

selection for these
 variegation
due to
cytoplasmic
(maternal)
inheritance
of chloroplasts

in reality, mature
plants do not exist, they will die
as albino seedlings
 The Endosymbiotic Theory
– organelles evolved from eubacteria –
– that invaded archea (archebacteria) –

theory proposed decades ago,

now supported by DNA sequencing
 Organellar DNA
• mostly comes in circles
• most organelle proteins
are encoded in the nuclear
tRNA genome & imported
 • many organelle-produced
 proteins are membrane-
embedded (e.g., cytochrome)
 G-rich • also, organelles tend
C-rich to be more susceptible
 to antibacterial antibiotics
&…
• all lending support
 to the endosymbiotic theory
mitochondrial DNA Variation
& Human History
“mitochondrial Eve & human evolution

• Homo sapiens sapiens (mt-MRCA) 130,000 years

ago in Africa
• “Out of Africa” hypothesis
• 85,000 years ago
• supported by "Y-chromosomal Adam“
• Spincer wells concluded “all humans alive today
are descendent of single man who lived in africa
around 85000 yrs ago”
• Technique- molecular clock correlating elasped
time with observed genetic drift.
 Characteristics of
cytoplasmic inheritance
• Reciprocal differences
• Lack of segregation
• Somatic segregation
• Association with organelle DNA
• Nuclear transplantation
• Transfer of nuclear genome through back cross:
production of alloplasmic lines
• Mutagenesis
• Irregular segregation in biparental inheritance: plasma
genes from both parents are transmitted to the progeny,
it is known as biparental inheritance.
 Male sterility
• the incapacity of flowering plants to produce
or release functional pollens.
• Types
1. Phenotypic male sterility: caused by gametocides and
environmental factors
2. Genotypic male sterility: It is of two types:
 functional male sterility (pollen is viable but not release)
 true male sterility. The pollen sterility (true male sterility) is
of three types.
(A) Cytoplasmic MS (B) Genetic MS
(B) Cytoplasmic-genetic MS
 CGMS

S F
rr
rr

MS MF

S S
Rr
RR
MF MF

F
F RR
Rr

MF MF
 Maternal effect:
Phenotype of progeny determined by genotype of mother.

Genotype: DD (female) X dd (male)

Phenotype: Dextral sinistral

F1 Dd (dextral)

Selfing

Gametes: D and d

F2 1 DD : 2Dd : 1 dd
(all dextral)

Selfing

F3 DD; DD, Dd, dd; dd

3 Dextral : 1 sinistral
Transfer of CMS to a new strain
Strain A
S X
F Strain B
B rr rr

MS, female MF, male

F1 S F
rr X rr Strain B

MS

S F
BC1 X rr Strain B
rr
MS
Repeated backcrosses

BC6 or BC8 S
rr A new strain
 Maternally inherited characters
in human
• maternal diabetes
• Rh incompatibility
• phenylketonuria
• Left or right handedness
• Birth weight
• Myoclonic epilepsy
• ragged red fiber disease (MERRF)
• Fibers from proliferation of
aberrant mitochondria
• Mutation in mtDNA tRNA gene
 Plants
• Seed size
• Protein/ amino acid content
• Plant height
• Pod size etc
Feeding the Future Population
of the World

The Green Revolution

welcome!
Introduction
to Genetics
 Albinism
in the Hopis
The Importance of Genetics
• agriculture
 The Importance of Genetics
• medicine
– pharmaceuticals
– diagnostics
– therapy
 Recent Nobel Prizes
Medicine & Physiology
• 2007 Capecchi, Evans, Smithies - "for introducing specific gene
modifications in mice by the use of embryonic stem cells“
• 2009 Blackburn, Greider, Szostak - "for the discovery of how chromosomes
are protected by telomeres and the enzyme telomerase”
• 2010 Edwards - "for the development of in vitro fertilization”
• 2011 Beutler, Hoffman, Steinman - "for their discoveries concerning the
activation of innate immunity"
• 2012 Gurdon, Yamanaka – "for the discovery that mature cells can be
reprogrammed to become pluripotent”

Chemistry
• 2008 Shinomura, Chalfie, Tsien- “for the discovery and development of the
green fluorescent protein, GFP"
• 2009 Ramakrishnan, Steitz, Yonath - "for studies of the structure and
function of the ribosome"
Oliver Smithies

“for introducing specific gene modifications

in mice by the use of embryonic stem cells”
 The Importance of Genetics

• a major role in modern biology

• genetic diversity & evolution
• divisions of genetics
• model genetic organisms
Divisions of Genetics
Integration of Genetics

GENOMICS
A Brief History of Genetics
A Brief History of Genetics
• natural selection
• artificial selection
 The Rise of Genetics

preformationism acquired reproduction

characteristics via germ line
Lamarck
~1809
Weismann ~1882
Charles Darwin Gregor Mendel
“On the Origin Laws
of Species” of Inheritance
1859 1865/1900
 Charles Darwin’s
Fundamental Insight
Heritable variation
in fitness
(survival & reproduction)
drives evolution
by natural selection.
 Gregor Mendel’s
Principles of Inheritance
• The Principle of Particulate
Inheritance
• The Principle of Dominance
• The Law of Segregation
• The Law of Independent
Assortment
 Modern Genetics
• blending vs particulate inheritance
• biometricians vs mutationists
• selection vs mutation
• Darwinists vs Mendelians
• the Modern Synthesis:
both mutation & selection underlie (are
the basis of )
genetics and evolution
 Ultra-Modern Genetics
• the elucidation of the structure of
DNA – the double helix
• cracking the genetic code
• biotechnology
• genomics
• the human genome
• and onward…
the double helix
DNA - 1953

Watson & Crick

the double helix
DNA - 1953

Rosalind Franklin
 Basic Concepts in Genetics
• Cells are of two basic types:
eukaryotic and prokaryotic
• The gene is the fundamental unit
of heredity
• Genes come in multiple forms
called alleles
• Genes confer (encode) phenotypes
• Genetic information is carried in DNA
and RNA
 Basic Concepts in Genetics
• Genes are located on chromosomes
• Chromosomes separate through
the processes of mitosis and meiosis
• Genetic information is transferred
from DNA to RNA to protein
• Mutations are permanent, heritable,
changes in genetic information
 Basic Concepts in Genetics
• Some traits are affected
by multiple factors
• Evolution is genetic change
what is life?
 traits Q:
folding what
& function is
protein life
translation ?
RNA
transcription
DNA
replication

A: gene replication & expression

A major theme of this course…

…taking the gene’s eye view

 what is life?
within a generation  in 2 biological
dimensions?


 

between generations
 what is life?
 in 2 biological
dimensions?



mitosis

 

meiosis
 what is life?
 sometimes
it takes two


 

fusion
 
what is life?
Development


 

Reproduction
phenotype 


Life is heredity
plus environment.

— Luther Burbank
(1849-1926)

genotype 

P=G+E
 Landauer’s principle

2
cm = E = infokTln2
 Genetics
is Information Theory
& Information Technology
• Reproduction: The Propagation
of Information
• Development: The Expression
of Information
 

 

& recombination! what is life?

 Universal Darwinism
Heritable variation in fitness
(survival & reproduction)
drives evolution
by natural selection.
• Information accumulates
as energy flows
& matter cycles.
• Life diversifies.
• Life complexifies.
Six Model Organisms
 how much DNA does it take to make a …?
how many genes does it take to make a …?
how many cells does it take to make a …?
#
# Model Genus & species length mass chrom # DNA genes # cells
The bacteriophage λ
0 200nm 1pg 1 circle 58.5kbp 55 0
Virus
Bacter- Escherichia coli
1 1.5µm 1ng 1 circle 4.64mbp 4 000 1
ium
Baker’s Saccharomyces
2 2µm 4ng 16 pair 12mbp 6 144 1
Yeast cerevisiae
The Caenorhabditis
3 1mm 300ng 5 pair 103mbp 20 500 959
Worm elegans
Drosophila
4 The Fly 2.5mm 1mg 4 pair 175mbp 14 000 1 000 000 000
melanogaster
The Arabidopsis
5 15cm 10g 5 pair 125mbp 25 700 15 000 000 000
Plant thaliana
The Mus musculus
6 6.5cm 20g 20 pair 2.6bbp 26 762 30 000 000 000
Mouse
 Us Homo sapiens 1.61m 64kg 23 pair 3.2bbp 24 000 100 trillion
what is a gene?
information

gene

matter energy
 Genetics & Values
Ethics

Esthetics Ecology

Economy