Q: Why is

there sex?
itd be much faster not to have to find a mate
- just replicate on your own

sexual
reproduction

asexual
reproduction

A: Sexual reproduction increases genetic diversity

X and Y are sex determining

chromosomes in humans and
flies
Homologous
chromosomes
X and Y have
different loci

behave as homologous
chromosomes during
meiosis in males
Males are hemizygous
for the X chromosome

XX: female
XY: male

Another type of sexual lifestyle:

elegans

C.

Males: animals with sperm

only that mate with
hermaphrodites

Hermaphrodites: selffertilizing animals with sperm

and eggs

Another type of sexual lifestyle: C.

elegans
Figure 5-3

XX

hermaphrodite

XO (this means 1X)

male

XO can occur by nondisjunction

Convenient for genetics to self and cross-fertilize

Many ways to determine sex

Drosophila,
mammals

homogametic: XX

heterogametic: XY

C. elegans

homogametic: XX

heterogametic: XO

heterogametic: ZW

homogametic: ZZ

XX ; AA: diploid

X ; A: haploid

birds, snakes,
butterflies
ants, bees, wasps
some reptiles & fish

26C

temperature!

29C

Sex chromosomes in humans

XX is female, XY is male
How is sex determined?
Different possibilities
2Xs determine a female, (if not, a male)
Y determines a male

Sex determination in humans

Insight into this question was gained from
syndromes with unusual #s of sex
chromosomes
Klinefelter syndrome: XXY
if 2 Xs determine female - XXY would be female
If Y determines a male, then XXY is male

Turner syndrome: XO (1X)

if 2X determines female, then XO is male
if Y determines male, then XO is female

Karyotype of Klinefelter syndrome

(47,XXY)

Figure 5-5

Karyotype of Turner syndrome

(45,X)

Figure 5-5

Whats on the Y chromosome?

actually ~75-90 genes on Y chromosome
sex-determining region
Y

Figure 5-6

SRY is a region (gene) on the Y

chromosome that makes the TDF protein
TDF: testis determining factor: specifies
male-ness
SRY deletion in Y causes XY to be female
SRY is necessary to be physiologically male

SRY attachment to X causes XX to be male

SRY is sufficient to be physiologically male

TDF is a transcription factor that is a

master switch that causes indifferent
gonads to become testes
just the first step in development - other genes
need to be present to complete male
development

genital development is a
coordinated biochemical dance

gender gets complicated

XY female
androgeninsensitivity
syndrome
Nikki Araguz
can get complex
legally if people dont
have biology
knowledge

X-linked traits
Males are hemizygous, meaning they
have only one chromosome of the pair
(one X)
Therefore they need only 1 recessive
allele to show an X-linked trait

Thomas Hunt Morgan

Was using radiation and

chemicals to cause
mutations in fruit flies,
Drosophila melanogaster.
Noticed a white-eyed
mutant male fly in 1910.

X-linked traits inherited differently

depending on gender of affected
parent
cross A
X

cross B
X

F1

F1

all F1 are red-eyed

All males have white eyes
All females have red eyes

X-linkage in Drosophila

Thomas H. Morgans numbers

for F2s

The F1 generation was

different depending on the
gender of the parents.

Continued to see difference in

F2 depending on sex of
original P parents

Color-blindness in humans
is usually an X-linked trait
What number do you see below?
3
8
nothing

8% of males are color blind,

0.5% of females are color blind

Pedigree for an X-linked recessive trait

(like color blindness)

Characteristics of an X-linked
recessive trait
mostly in males
affected allele came from mother

often goes from mother to son

affected mothers pass trait to all of their sons

never father to son

affected males have:
all daughters who are carriers
no sons who are affected (unless mother was also
a carrier)

Hemophilia: another X-linked

trait
Defect in blood clotting factor
80% of cases caused by defect in factor VIII

bleeding

X X

factor VIII
enzyme

blood
clot

hemophilia (a condition of easy bleeding)

Pedigree nomenclature for

carriers of trait
Carries the trait

Exhibits the trait

Hemophilia: trait that passed

through royal families

Hemophilia: bleeding disorder that can cause death

Clinical Question:
Duchenne muscular dystrophy is
caused by a recessive X-linked allele.
A man with this disorder:

1) could have inherited it from either parent.

2) must have inherited it from his mother.
3) must have inherited it from both parents.
4) would pass it along to all of his children.
5) would pass it along to only his sons.

Match the pedigree

to the mode of inheritance
1

? Autosomal recessive
1

? Autosomal dominant
1

? X-linked recessive
1

? X-linked dominant
1

Sex-limited inheritance
autosomal gene affects trait
trait ONLY expressed in one sex
cock feathering
Figure 4-13

Genotype

Female

Male

HH

Henfeathered

Henfeathered

Hh

Henfeathered

Henfeathered

hh

Henfeathered

Cockfeathered

Sex-influenced inheritance
autosomal gene affects trait
trait expressed to a lesser degree in one
sex: e.g. baldness
Figure 4-14

Genotype

Female

Male

BB

Bald

Bald

Bb

Not bald

Bald

bb

Not bald

Not bald

Sex-influenced inheritance
autosomal gene affects trait
trait expressed to a lesser degree in one
sex: e.g. baldness

Organelle inheritance
(e.g. mitochrondrial inheritance)
In addition to DNA in the nucleus, there is also
DNA in the mitochondria
nuclear genome

mitochondrial genome

How are mitochondria inherited?

remember gametogenesis difference

Example of mitochondrial
mutation in humans
Myoclonic epilepsy and ragged-red fiber
disease (MERRF)

Translation defect in
mitochondria

Defects in muscle cells of MERRF patients

Children of affected mothers have trait
Children of affected fathers do not

Characteristics of
mitochondrial mutations

How do organisms deal with the

difference in chromosome #
between males and females?

male

female

Do females express twice as much

gene product from X-linked genes?
NO
Dosage compensation addresses this problem

Dosage compensation: how to

deal with different dosesof
X?

Different solutions to this problem!

Worms express 1/2 as

much X in hermaphrodites

Flies express twice as

much X in males
Humans
inactivate one X
in females

XX

XO

XX

XY

XX or XX

XY

Humans inactivate one X

chromosome
Silence one female X chromosome so
males and females express the same
amount
X-inactivation: causes Barr body

inactivated
X chromosome

Figure 5-7

X inactivation follows N-1 rule

N is # of X chromosomes
# of Barr bodies is N-1

Figure 5-8

Lyon hypothesis
Mary Lyon discovered X-inactivation in
1961
It is random which X chromosome
is inactivated: maternal or paternal
X-inactivation occurs early in
embryonic development.

X-inactivation is maintained
through several cell divisions
Creates clones or groups of cells that
have one chromosome inactivated
maternal

paternal

this tissue only

expresses
maternal X
chromosome

this tissue only

expresses
paternal X
chromosome

Result is mosaic expression

Female mammals are mosaics of X

chromosome expression:
some cells express maternal X
some cells express paternal X

maternal

paternal
Each cell can be
functionally hemizygous
for X, like males

Female cat coloration: due to X

inactivation
Which X chromosome is inactivated is
random: paternal or maternal
Coloration
tortoiseshell

Dinah

X inactivation

Maternal effect
Offsprings phenotype is under the control
of nuclear gene products present in the
egg
Genotype of female parent, NOT the
genotype of the offspring determines the
phenotype of the offspring

Maternal effect example

Pigmentation in Ephestia (meal moth)
Brown

Red

Brown

Red

Brown

Brown

Red

Brown

Red

Brown

Brown

Red

Brown

Red

Brown

Brown

Red

Brown

Red

Brown

An enzyme was left over in the oocytes from mom.

This is sufficient to make pigment for the larvae.
The adults eventually become red-eyed and pale
as we would expect.

Other genetic terms:

Penetrance & Expressivity
Penetrance
The percentage of individuals that show at
least some degree of expression of a mutant
phenotype.
e.g. If 15% of mutant flies show the wild-type
appearance, the mutant gene is said to have
a penetrance of 85%.

Other genetic terms:

Penetrance & Expressivity
Expressivity
The range of expression of a mutant
phenotype.
e.g. Flies homozygous for the recessive
mutant eyeless gene yield phenotypes that
range from having normal eyes to partial
reduction in size of eyes to having no eyes at
all.

Penetrance: the % of population

that expresses the phenotype
15%

wild-type
or normal

40%

small eyes

45%

no eyes

eyeless
mutation

Mutant gene has a penetrance of 85%

Expressivity: same mutation

can cause a range of
phenotypes
normal eyes

eyeless
mutation

small eyes

no eyes

Incomplete penetrance of a mutation

can alter Mendelian ratios
Not all animals with the mutation show the
phenotype
If mutations are incompletely penetrant, this can
alter Mendelian ratios
For example, if a recessive mutation (h) is 50%
penetrant when homozygous, a monohybrid
cross could give this ratio in the F2
7/8 wildtype (1/4 HH, 1/2 Hh, 1/8 hh)
1/8 mutant (hh)

Conditional mutations
The phenotype of a mutation can
depend on environmental conditions
e.g. temperature-sensitive mutations (ts)
Enzyme that produces
pigment is only functional at
the lower temperatures of
the extremities.

Epigenetics
An epigenetic trait is a stable, mitotically,
and meiotically heritable phenotype that
results from changes in gene expression
without alterations in the DNA sequence
Epigenetics is the study of the ways in
which these changes alter cell- and tissuespecific patterns of gene expression.

Epigenetic Alterations to the

Genome
There are three major epigenetic
mechanisms:
Reversible modification of DNA by
addition/removal of methyl groups
Alteration of chromatin by addition/removal of
chemical groups to histone proteins
Regulation of gene expression by small,
noncoding RNA molecules

ST Figure 1-2

Histone
Modification
and
Chromatin
Configuration

ST Figure 1-4

MicroRNAs
In addition to DNA methylation and histone
modification, small, noncoding RNA molecules
called microRNAs (miRNAs) also participate
in epigenetic regulation of gene expression.
Involved in controlling the pattern of developing
embryos and in the timing of developmental
events and physiological processes such as cell
signaling
Also play roles in the development of
cardiovascular disease and cancer

Genomic imprinting
Diploids have pairs of homologous
chromosomes
usually genes are expressed from both
chromosomes
sometimes genes are only expressed on
chromosome from one parent or the other:
imprinting

Igf2 gene
Insulin-like growth factor ( Igf2 )
Igf2 is important for normal growth.
If mouse inherits normal Igf2 genes,
mouse is normally sized.
If mouse inherits mutant Igf2 from mom,
mouse is normally sized.
If mouse inherits mutant igf2 from dad,
mouse is dwarf.

Igf2 gene

ST Table 1.1

Paternal = Prader-Willi
Maternal = Angelman

Epigenetics and the Environment

Environmental agents, including nutrition,
chemicals, and physical factors such as
temperature, can alter gene expression by
affecting the epigenetic state of the
genome.
There is indirect evidence that changes in
nutrition and exposure to agents that affect
the developing fetus can have detrimental
effects during adulthood.

Epigenetics and the Environment

Women pregnant during the 19441945
famine in the Netherlands had children with
increased risk of obesity, diabetes, and
coronary heart disease.
As adults, these individuals had significantly
increased risks for schizophrenia and other
neuropsychiatric disorders.

The F2 generation also had abnormal

patterns of weight gain and growth.
Similar results were found in adult children of
Chinese women pregnant during the 1959
1961 famine.