Genes and sex determination

March 31, 2015

Albrecht Dürer - Adam and Eve, 1504

János Szabad
Department of Biology
Faculty of Medicine
University of Szeged
Somogyi str. 4
H-6720 Szeged, Hungary
E-mail: szabad.janos@med.u-szeged.hu
 Types of reproduction

Type of Germ
For Against
reproduction cells?

- Fast conquer of the

environment - Low genetic
Asexual No variability
- Cheap: no need for
germ cells and mates

- Slow conquer of the

environment
Sexual Yes - High genetic variability - Expensive: germ cell
production and
finding mate
 Meiosis

Second meiotic division

The three sources of genetic variability:
- mutations

First meiotic division

- independent assortment of the chromosomes
- crossing over

Crossing over
Replication

One possibility

Diploid
germ-line cell

Another possibility Haploid

germ cells
Oysters, among others, have the capability of
alternating their sex several times within
their life span.
Sex determination in reptilians

Crocodile embryos do not have sex

chromosomes, and unlike humans,
sex is not determined genetically. At
the egg incubation temperature of
29.4 oC all the hatchlings will all be
female. At 31.7 oC equal numbers of
healthy male and female hatchlings
result. At 32.8 oC only males are
produced. The temperature-sensitive
period is between 7 and 21 days of
incubation
Saccharomyces cerevisiae
(baker's yeast)
Mating type (a or α) is determined by a
single locus, MAT, which in turn governs
the sexual behavior of both haploid and
diploid cells.

Two haploid yeast of opposite mating types secrete

pheromones, grow projections and mate.
http://en.wikipedia.org/wiki/Mating_of_yeast
Neurospora crassa
(pink bread mold)

Mating type (A or a) is determined

by a single locus, MAT, which
governs the sexual behavior of the
filamentous fungus.

http://www.metamicrobe.com/neurospora/
 Haploid diploid sex determination
In the „haplodiploidy” sex determination system sex is determined by the
number of sets of chromosomes an individual receives. The males develop
from unfertilized eggs and are haploid, the females develop from the fertilized
eggs and are dipolid. It determines sex, among others, in bees, wasps and ants.
Caenorhabditis elegans
(a nematode or roundworm)

Hermaphrodite

Male
The C. elegans species consists of hermaphrodites and males.
Hermaphrodites are essentially female animals that are self-fertile.
They make some sperm early during development and subsequently
switch to oogenesis. Under continuous growth conditions C. elegans
populations consist predominantly of self-fertilizing hermaphrodites,
and only 0.01-0.1% males. Development of the hermaphrodites and
the males appears to be determined irreversibly at fertilization by the
ratio of X chromosomes to sets of autosomes (X:A ratio) of the
embryo: XX embryos develop as hermaphrodites and X0 embryos as
males.
The X:A ratio is interpreted to specify sexual cell fates. During early
embryogenesis dosage compensation genes (e.g. xol-1, sex-1, sdcs)
are sensitive to the X:A ratio. Subsequently a number of sex
determination genes (e.g. her-1 ,tra-2, fem-1,2,3, tra-1) are activated
to control the final developmental outcome.
http://groups.molbiosci.northwestern.edu/morimoto/research/research_sex.html
Sex determination in Drosophila melanogaster

Male Female germ cells

germ cells X X
X XX XX
Y XY XY
http://openi.nlm.nih.gov/detailedresult.php?img=2987205_11692_2010_9101_Fig3_HTML&r=4
http://cmgm.stanford.edu/devbio/baker/Hierarchy.htm
http://cmgm.stanford.edu/devbio/baker/Hierarchy.htm
The primary signal determining whether the fly develops as a male or female is the number of X
chromosomes relative to the number of autosomes (non-sex chromosomes) in a cell (the X:A
ratio). Individuals carrying one X chromosome and two sets of autosomes are male (X:A=0.5),
whereas individuals with an equal number of X and autosomal chromosomes are female
(X:A=1).
In Drosophila the Y chromosome does not play a role in sex determination like in humans!
The first response to the ratio of X:A is the activation or inactivation of the Sex-lethal gene
(SXl). In the case of a female fly the gene is activated and the SXL protein is produced; in male
flies the SXl gene is inactive and no SXL protein is produced.
SXL (Sex-lethal) - The major player: A protein with three responsibilities
In the female fly, the SXL protein determines all aspects of terminal differentiation. It activates a
pathway of reactions that leads to female-specific gene expression. Each subsequent gene
controls only one “following” gene in the cascade.
The SXL protein determines the splicing pattern of the tra (transformer) transcript in such a way
as to produce an active TRA protein. The TRA protein itself is an RNA-binding protein that
ensures that the following dsx (doublesex) RNA is spliced in a female-specific way.
DSX – The doublesex protein
TRA can form dimers with the TRA2 protein and causes splicing of DSX to a short form in
females (DSXF). In males, where no SXL or TRA protein is made, DSX is spliced into a longer
form (DSXM). DSXF triggers female gene expression and DSXM (in the male) blocks female
gene expression.
The highly regulated alternative splicing pathway therefore determines whether ‘male’ or
‘female’ genes are expressed to determine the sex of the fly.
Sex determination in birds

Male Female germ cells

germ cells Z W
Z ZZ ZW
Z ZZ ZW
The ZW sex-determination system determines the sex of offspring in
birds, some fish and crustaceans, some insects including butterflies and
moths), and some reptiles, including komodo dragons.

G-banded karyotype of chicken macro-chromosomes (of 76)

♀
In silk moths the W
♂ chromosome carries
the female-determining
genes.
Sex determination in humans

Male Female germ cells

germ
cells X X
X XX XY
Y XX XY Rubens, 1597
 Types of sex determination

Type Example

Environmental Oysters, alligators, turtles

Alleles of two genes Yeast, pink bread mold

Haplodiploidy Bees, wasps, ants

X/A ratio Caenorhabditis elegans, Drosophila

Key gene on a sex Birds, moth, butterflies, human
chromosome
 The human chromosome set

chromosomes
Sex
Autosomes

19 20 21 22 Y
16 17 18
10 11 13 14 15
8 9 12
3 7 50 million X
4 5 6 base pairs
1
2

The human genome is composed from about 3.2x109 base pairs packed
into 24 chromosomes. This DNA is about one meter long and contains
about 20-23 thousand genes.
 Pseudoautosomal
The human X and Y chromosome
region

p NR0B1
SRY or TDF
p
Centromere
X
q

q
Y
Y

Pseudoautosomal
X region
 The human Y chromosome
PAR The nine genes in the pseudoautosomal regions are
SRY inherited as any of the autosomal genes. Males have two
p copies of these genes: one in the pseudoautosomal region
of their Y, the other in the corresponding portion of their
X chromosome.
q 95% of the Y chromosome is between the pseudo-
autosomal regions with 24 genes in here. Half of this
region is genetically-barren heterochromatin. Of the 24
PAR genes in the euchromatin some encode proteins used by
all cells, others encode proteins that function only in the
testes. A key player in this latter group is the SRY gene
(sex-determining region on Y).
SRY is also known as TDF, testis determining factor.
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/SexChromosomes.html
 The SRY protein
- is a transcription factor,
- is composed from 204 amino acids,
- is expressed from the 7th week of
embryogenesis,
- it initiates testis differentiation by
activating male-specific transcription
factors that allow the yet bipotential
DNA cells to differentiate and proliferate.
- The XX mice with the Sry transgene
(inserted into either of the
chromosomes) are males, a
phenomenon called sex reversal.
 PAR The human X chromosome
The X chromosome in humans
spans more than 153 million base
p pairs and carries about 2,000 out
NR0B1 DAX1 of 20,000 - 23,000 genes.

The NR0B1 (nuclear receptor subfamily 0, group B, member 1)

gene encodes DAX1 protein (dosage-sensitive sex reversal,
adrenal hypoplasia critical region, on chromosome X, gene 1).
The DAX1 protein plays an important role in development of
several hormone-producing tissues including the adrenal glands,
the pituitary gland and the hypothalamus in the brain and the
q male and female reproductive structures (the testes and ovaries).
DAX1 controls the activity of genes in the cells that form these
tissues during embryonic development and in regulating
hormone production in these tissues after they formed.

PAR http://en.wikipedia.org/wiki/DAX1
Differentiation of the outer genitalia

Homologous organs
develop from the same
embryonic tissue.

http://classes.midlandstech.edu/carterp/Courses/bio211/Chap27/Reproductive_System.html
 apoptosis
Death through
Formation of the internal genitalia

http://kcampbell.bio.umb.edu/MamTox/Presentations/Session13/INTREPRO.GIF
 Differences between the
female and male brains
There are distinct differences
between the male and female brains
already at the 26th weeks of
pregnancy: the corpus callosum, for
example, is thicker in the female than
in male fetuses.
The adult male brains contain about
6.5 times more gray matter than the
women.
The female brains have more than 9.5
times as much white matter than the
male brains.
The frontal area and the temporal
area of the cortex are more precisely
organized in women, and are bigger
in volume than in males.
Treatment of female rats Treatment of male rats
Treatment of female rats Treatment of male rats
 Gene action and outcome

NR0B1 DAX1

SRY

X Y
X
Y

NR0B1

mutant allele
SRY loss-of-function

XY pseudohermaphrodite
(testicular feminization)
 

X
Y
SRY
mutant allele
NR0B1 loss-of-function

XY pseudohermaphrodite
(testicular feminization)
Female spotted hyenas have pseudo-penis