This lecture is designed to prepare students to:

1. Describe the genetic basis for sex differentiation in some example

systems

2. Conceptually link previously established terminology to concepts that

directly apply to sex determination in humans.

Asexual reproduction generates genetically identical offspring

Genetic variation = presence of alternative alleles
Individuals receive alternative alleles:
1. Mutation
2. Horizontal gene transfer
Example: bacterial binary fission

Replicated chromosome Genetically identical daughter cells

production generates offspring with allele combinations unique to eithe

Offspring are genetic hybrids of parents
Individuals receive alternative alleles:
1. Mutation
2. Horizontal gene transfer
3. Different parental alleles
Requires pairs of individuals to exchange genetic material

Requires different sexes in a population

Sexual reproduction requires individuals to be sexually differentiated

In C. elegans: Absence of X determines maleness
Sex differentiation often relies on presence/absence of specific
chromosomes
Homogametous: A sex whose gametes have one possible sex
chromosome compositionExample:
Heterogametous:
A sex whose
gametes
have multiple possible sex
Caenorhabditis
elegans
(C. elegans)
chromosome composition
XX

XX

XX

Presence of second
X determines
maleness
Male
gametes = X
or No X

Sexual reproduction requires individuals to be sexually differentiated

In C. elegans: Absence of X determines maleness
Sex differentiation often relies on presence/absence of specific
chromosomes
Homogametous: A sex whose gametes have one possible sex
chromosome composition
Example:
Heterogametous:Caenorhabditis
A sex whose gametes
multiple possible sex
elegans have
(C. elegans)
chromosome composition
XX

Hermaphrodi
tes are
homogamet
ous

XX

XX

Males are
heterogamet
ous

Sexual reproduction requires individuals to be sexually differentiated

In humans: Presence of Y determines maleness
Sex differentiation often relies on presence/absence of specific
chromosomes
Homogametous: A sex whose gametes have one possible sex
chromosome composition
Heterogametous: A sex whoseExample:
gametes have multiple possible sex
Homo sapiens (Humans)
chromosome composition

Females can only generate X gametes Males can generate X or Y gametes

Heterogametous
Homogametous

Sexual reproduction requires individuals to be sexually differentiated

In Birds: Presence of two Z chromosomes determines maleness
Sex differentiation often relies on presence/absence of specific
chromosomes
Homogametous: A sex whose gametes have one possible sex
chromosome composition
Example:
Heterogametous: A sex whose gametes
have multiple possible sex
Birds
chromosome composition

A = Generic representation of autosomes

SRY = Sex-determining region Y
DMRT1 = Bird equivalent of SRY

The X and Y chromosomes are not members of a homologous pair

For humans:
X and Y dont have same genes but different alleles
Evolved from the same autosome (~200 -300 years ago)
Now, ~3% of original shared genes remain
Remaining shared genes are dosage dependent (haploinsufficient)
Y contains at least 18 genes required but not for maleness

Y has regions that are homologous and nonhomologous to X

Y Chromosome

PAR (Pseudoautosomal region):

homologous to X-chromosome, can
synapse and recombine with X
SRY (Sex-determining region Y): gene
that encodes testis-determining factor
Present in all mammals
Active @ ~6 8 weeks of embryo
development
Activate gonad differentiation to testes
Phenotypic females that are XY have
mutation in SRY
Phenotypic males that are XX have SRY
translocation on their X
MSY (Male-specific Y): Limited synapse
or recombination with X
8 Mb of p arm
14.5 Mb of q arm
Contains euchromatin and
heterochromatin
Contains three sequence-related regions
X-transposed
X-degenerate
Ampliconic

Y has regions that are homologous and nonhomologous to X

Y Chromosome
PAR (Pseudoautosomal region):
homologous to X-chromosome, can
synapse and recombine with X

Why is it essential that the X and Y synapse at al

Y has regions that are homologous and nonhomologous to X

Y Chromosome

SRY (Sex-determining region Y): gene

that encodes testis-determining factor
Transcriptional regulator

What is a transcriptional regulator?

Transcription initiation by eukaryotic RNA Pol II is controlled

Enhancer: Transcription from a promoter is upregulated near this element

Often can be moved to other sites near a gene
Sequence can be inverted
Includes many complex nucleotide repeats (often ~100 bp)
Silencer (Not shown): Transcription from a promoter is downregulated near
this element

2015 Pearson
Education, Inc.

Figure 17-8

Y has regions that are homologous and nonhomologous to X

Y Chromosome

SRY (Sex-determining region Y): gene

that encodes testis-determining factor
Transcriptional regulator
Present in all mammals
Active @ ~6 8 weeks of embryo
development
Activate gonad differentiation to testes
Phenotypic females that are XY have
mutation in SRY
Phenotypic males that are XX have SRY
translocation on their X

Y has regions that are homologous and nonhomologous to X

Y Chromosome

MSY (Male-specific Y): Limited synapse

or recombination with X
8 Mb of p arm
14.5 Mb of q arm
Contains euchromatin and
heterochromatin

Eukaryotic genomic DNA is packaged/organized as nucleosomes in chromatin

Spacer regions
Variable length
Multiple H1

Eukarytoic DNA is divided into two regions

Euchromatin
Uncoiled and active
Appears unstained during interphase
Long spacer regions

Heterochromatin
Condensed areas are mostly inactive
Appears stained during interphase
Short spacer regions

Y has regions that are homologous and nonhomologous to X

MSY (Male-specific Y): Limited synapse or
recombination with X
8 Mb of p arm
14.5 Mb of q arm
Contains euchromatin and
heterochromatin
Which likely doesnt contain genes?
Heterochromatin
Contains satellites
Remember: Microsatellites
= most common method for
determining human kinship
10s 100s of 2-4 nt
repeats (most common
= CA)
Variability: not in
sequence, but number of
repeats

Y has regions that are homologous and nonhomologous to X

Yp11.32
Yp11.31
Yp11.2
Yp11.1
Yq11.1
Yq11.21
Yq11.221
Yq11.222
Yq11.223
Yq11.23

Yq12

MSY (Male-specific Y): Limited synapse or

recombination with X
8 Mb of p arm
14.5 Mb of q arm
Contains euchromatin and
heterochromatin
Which likely doesnt contain genes?
Heterochromatin
Contains satellites
Remember: Microsatellites
= most common method for
determining human kinship
10s 100s of 2-4 nt
repeats (most common
= CA)
Variability: not in
sequence, but number of
repeats

Regions of chromosomes are defined by their G-banding

Single chromatid displayed

2015 Pearson
Education, Inc.

Figure 12-13

Y has regions that are homologous and nonhomologous to X

Yp11.32
Yp11.31
Yp11.2
Yp11.1
Yq11.1
Yq11.21
Yq11.221
Yq11.222
Yq11.223
Yq11.23

Yq12

MSY (Male-specific Y): Limited synapse or

recombination with X
8 Mb of p arm
14.5 Mb of q arm
Contains euchromatin and
heterochromatin
Which likely doesnt contain genes?
Heterochromatin
Contains satellites
Remember: Microsatellites
= most common method for
determining human kinship
10s 100s of 2-4 nt
repeats (most common
= CA)
Variability: not in
sequence, but number of
repeats

Y has regions that are homologous and nonhomologous to X

Y Chromosome

MSY (Male-specific Y): Limited synapse or

recombination with X
8 Mb of p arm
14.5 Mb of q arm
Contains euchromatin and
heterochromatin
Which likely doesnt contain genes?
Heterochromatin
Contains satellites
Which likely contains genes?
Euchromatin
~156 coding regions
78 for proteins
60 belong to 1 of 9
classes
Members of
each class
>98% ID
(introns &
exons)
Through evolution, which chromosomal
rearrangement could lead to 60 multicopy genes?

Y has regions that are homologous and nonhomologous to X

Y Chromosome

MSY (Male-specific Y): Limited synapse or

recombination with X
8 Mb of p arm
14.5 Mb of q arm
Contains euchromatin and
heterochromatin
Which likely doesnt contain genes?
Heterochromatin
Contains satellites
Which likely contains genes?
Euchromatin
~156 coding regions
78 for proteins
60 belong to 1 of 9
classes
Members of
each class
>98% ID
(introns &
exons) coding genes
Consider:
BLAST query = 1 of the 60 protein
BLAST subject = Homo sapiens genome
How many homologs would you expect to find? (0, 1, or >1?)

Y has regions that are homologous and nonhomologous to X

Y Chromosome

MSY (Male-specific Y): Limited synapse or

recombination with X
8 Mb of p arm
14.5 Mb of q arm
Contains euchromatin and
heterochromatin
Which likely doesnt contain genes?
Heterochromatin
Contains satellites
Which likely contains genes?
Euchromatin
~156 coding regions
78 for proteins
60 belong to 1 of 9
classes (multicopy)
Members of
each class
>98% ID
(introns &
exons)
18genes
are single copy
Consider:
BLAST query = 1 of the 2 protein coding
2 are 93.6% ID
BLAST subject = Homo sapiens genome
(exons only)
How many homologs (>80% coverage, >30%ID) would you expect to find? (0, 1, o

Y has regions that are homologous and nonhomologous to X

Y Chromosome

MSY (Male-specific Y): Limited synapse or

recombination with X
8 Mb of p arm
14.5 Mb of q arm
Contains euchromatin and
heterochromatin
Which likely doesnt contain genes?
Heterochromatin
Contains satellites
Which likely contains genes?
Euchromatin
~156 coding regions
78 for proteins
60 belong to 1 of 9
classes (multicopy)
Members of
each class
>98% ID
(introns &
exons)
Consider:
BLAST query = 1 of the 2 proteins 18 are single copy
2 are 93.6% ID
BLAST subject = Homo sapiens genome
(exons only)
How many homologs (>80% coverage, >30%ID) would you expect to find? (0, 1,

Y has regions that are homologous and nonhomologous to X

Y Chromosome

MSY (Male-specific Y): Limited synapse or

recombination with X
8 Mb of p arm
14.5 Mb of q arm
Contains euchromatin and
heterochromatin
Euchromatin region has three classes
of sequence
Based on the name, what is the likely sequence
X-transposed
relationship between this class and a region of
the X chromosome?

Y has regions that are homologous and nonhomologous to X

Note: The red arrows indicate direction of sequence relative to X-chromosome

Y Chromosome

MSY (Male-specific Y): Limited synapse or

recombination with X
8 Mb of p arm
14.5 Mb of q arm
Contains euchromatin and
heterochromatin
Euchromatin region has three classes
of sequence
X-transposed ~99% ID to Xq21
No synapse/recombination
with X

Y has regions that are homologous and nonhomologous to X

Y Chromosome

MSY (Male-specific Y): Limited synapse or

recombination with X
8 Mb of p arm
14.5 Mb of q arm
Contains euchromatin and
heterochromatin
Euchromatin region has three classes
of sequence
X-transposed ~99% ID to Xq21
X-degenerate ( codon
degeneracy)
27 genes
60 90% ID with X
chromosome genes
(exons & introns)
Are the 27 genes likely to have
homologs on X? (by the evolutionary

Y has regions that are homologous and nonhomologous to X

Y Chromosome

MSY (Male-specific Y): Limited synapse or

recombination with X
8 Mb of p arm
14.5 Mb of q arm
Contains euchromatin and
heterochromatin
Euchromatin region has three classes
of sequence
X-transposed ~99% ID to Xq21
X-degenerate ( codon
degeneracy)
27 genes
60 90% ID with X
chromosome genes
(exons
introns)
Pseudogenes = sequences very similar
to &
known
functional genes

13
=
pseudogenes
Often: frameshift or nonsense mutation

How is this consistent with the X-degenerate genes as homologs

Y has regions that are homologous and nonhomologous to X

Y Chromosome

MSY (Male-specific Y): Limited synapse or

recombination with X
8 Mb of p arm
14.5 Mb of q arm
Contains euchromatin and
heterochromatin
Euchromatin region has three classes
of sequence
X-transposed ~99% ID to Xq21
X-degenerate ( codon
degeneracy)
27 genes
60 90% ID with X
chromosome genes
(exons & introns)
13 = pseudogenes
Consider: Would one expect genes expressed from both X
14 = ubiquitously
and Y to be sex-specific and therefore gonad tissueexpressed (expressed in
specific?
all tissues)

Y has regions that are homologous and nonhomologous to X

Y Chromosome

MSY (Male-specific Y): Limited synapse or

recombination with X
8 Mb of p arm
14.5 Mb of q arm
Contains euchromatin and
heterochromatin
Euchromatin region has three classes
of sequence
X-transposed ~99% ID to Xq21
X-degenerate ( codon
degeneracy)
Ampliconic Satellites
Repeats of multicopy genes
Copy of genes varies within
the population
Consider: What is the term for describing a situation in
which a genes copy number varies among the population?

Y has regions that are homologous and nonhomologous to X

Y Chromosome

MSY (Male-specific Y): Limited synapse or

recombination with X
8 Mb of p arm
14.5 Mb of q arm
Contains euchromatin and
heterochromatin
Euchromatin region has three classes
of sequence
X-transposed ~99% ID to Xq21
X-degenerate ( codon
degeneracy)
Ampliconic Satellites
Repeats of multicopy genes
Copy number of genes varies
within the population (CNV)
Primarily expressed in testes
Consider: Why would it be surprising to find the genes from
the Ampliconic region in the X-transposed or X-degenerate
regions?

Y has regions that are homologous and nonhomologous to X

Y Chromosome

PAR (Pseudoautosomal region):

homologous to X-chromosome, can
synapse and recombine with X
SRY (Sex-determining region Y): gene
that encodes testis-determining factor
Present in all mammals
Active @ ~6 8 weeks of embryo
development
Activate gonad differentiation to testes
Phenotypic females that are XY have
mutation in SRY
Phenotypic males that are XX have SRY
translocation on their X

MSY (Male-specific Y): Limited synapse

or recombination with X
8 Mb of p arm
14.5 Mb of q arm
Contains euchromatin and
heterochromatin
Contains three regions of different
sequence relationships within each
region
Current working hypothesis:
X-transposed
1. SRY regulates autosomal genes for testes
formation
X-degenerate
2. In teste environment, cell signals control
male-specific genes on Y
Ampliconic

The X and Y chromosomes are not members of a homologous pair

For humans:
X and Y dont have same genes but different alleles
Evolved from the same autosome (~200 -300 years ago)
Now, ~3% of original shared genes remain
Remaining shared genes are dosage dependent (haploinsufficient)
Y contains at least 18 genes required but not for maleness

onsider: If X has genes not on Y, how do females avoid problems with gene dosa

The X and Y chromosomes are not members of a homologous pair

X
Chromosome

In females:
Genes that would not be on a Y chromosome are at 2X gene dosage
X-inactivation avoids problems, one X is converted to a Barr body
(Dosage compensation)
Highly compact (heterochromatic) = inaccessible for expression
Randomly, one X is inactivated early in development
Every daughter cell has the same X inactivated
Version of imprinting = Differential regulation of the same genes
on members of a homologous pair

The X and Y chromosomes are not members of a homologous pair

In females:
Genes that would not be on a Y chromosome are at 2X gene dosage
X-inactivation avoids problems, one X is converted to a Barr body
(Dosage compensation)
Highly compact (heterochromatic) = inaccessible for expression
Randomly, one X is inactivated early in development
Every daughter cell has the same X inactivated
Version of imprinting = Differential regulation of the same genes
on members of a homologous pair

This lecture is designed to prepare students to:

1. Describe the genetic basis for sex differentiation in some example

systems
. Which sex is homogametous? heterogametous?
2. Conceptually link previously established terminology to concepts that
directly apply to sex determination in humans.
. X and Y homologous pair?
. Haploinsufficient?
. Synapse and recombination?
. Transcriptional regulators?
. Chromosome structure?
. Chromosomal compaction?
. Chromosomal rearrangements?
. Chromosomal markers, including CNVs?
. Chromosomal demarcation?
. Evolutionary sequence relationship?
. Exon/intron splicing?
. Gene dosage?