5 Genetics and Evolution
5.4 Sex Determination
Sex determination
Dr V Malathi
Sex Chromosomes
In humans and in many other animal species the sex of the organism is determined by specific chromosomes.
• The chromosomes that carry those genes related to sexual characteristics are called the sex chromosomes.
• Experiments conducted by German biologist Hermann Henking in 1891 showed that sex chromosomes were unique from all other
chromosomes.
Henking was studying sperm formation in wasps. Henking saw that some wasp sperm cells had 12 chromosomes, while others had only 11.
• While observing the stages of meiosis that formed these sperm cells, Henking noticed that the twelfth chromosome looked different from all the others.
• He thus named this chromosome the “X element,” to represent its unknown nature.
• Henking hypothesized that this extra chromosome must play some role in sex determination in insects.
Humans and most other mammals have two sex chromosomes, the X and the Y.
• Females have two X chromosomes in their cells, while males have both X and a Y chromosomes in their cells.
• Egg cells all contain an X chromosome, while sperm cells contain an X or Y chromosome
Animals with two different sex chromosomes are of heterogametic sex. These are able to produce two types of gametes.
• While members of the homogametic sex can only produce one type of gamete.
• In humans (as well as many other animals), males are heterogametic, while females are homogametic .
• This system is reversed in butterflies and moths (order Lepidoptera): females are the heterogametic sex, while males are
homogametic
Sex Determination in Mammals
• In placental mammals, the presence of a Y chromosome determines sex.
• Normally, cells from females contain two X chromosomes, and cells from males contain an X and a Y chromosome.
• Occasionally, individuals are born with sex chromosome aneuploidies, and the sex of
these individuals is always determined by the absence or presence of a Y chromosome
The Y Chromosome
• The Y chromosome of the males is the smallest chromosome .
• It’s a kind of hemizygous- single chromosome.
• It is inherited from fathers to their male child.
• It has very few genes present on its single-arm, in comparison with other chromosomes.
• The Y chromosome evolved before 300,000 years ago from autosomes.
• The Y chromosome is the smallest acrocentric chromosome
• The size of it is 57,227,415bp.=57.2 Mb
• Genes on Y chromosome: around 200 in which the structure and function of only 50 to 60 genes are known to us.
• The centromere is located at the position of 10.4Mb.
• Only a single Y chromosome is present in the male individuals of the mammalian population
Note:
• kilo base pairs = 1,000bp
• 1 Mb (Mbp) = mega base pairs = 1,000,000bp
“Human male Karyotype after G-banding. Y chromosome highlighted” by National Human Genome Research Institute, via Wikimedia Commons is in the Public Domain, CC0
Structure:
• Structurally, the Y chromosome is a smaller- acrocentric chromosome having a short p arm and a long q arm.
• The p arm mostly contains genes and DNA sequences that are necessary for maleness, for example, the TDF and SRY.
• The short Yp regions are more euchromatin in nature, which is transcriptionally active.
• Around 95% portion of the Y chromosomes is dedicatedly present for maleness while the rest of the 5% region is known as PAR
pseudoautosomal regions. Usually, the PAR sequences are transcriptionally inactive.
• The centromere between the p and q arm helps in correct chromosomal segregation during the cell division. The centromere is
also heterochromatin, a transcriptionally inactive region.
• The approximate size of the Y chromosome is 59 million base pairs with 100 to 200 known genes. However, only 40 to 75 genes’ functions are known to us.
• Usually, the Y chromosome is almost the same in all other mammals as well.
• For instance, the Y chromosome of our closest relative chimpanzee is only 30% different in terms of sequences, not size.
Genes of Y Chromosome
| SRY | Sex determining region on Y |
| ZFY | Zinc finger protein |
| PRKY |
Protein kinase, Y linked
|
| TDF | Testing determining region |
| AMGL | Amelogenin |
| AZF1 | Azoospermia factor 1 |
| AZF2 |
Azoospermia factor 2
|
| DAZ | Deleted in azoospermia |
| UTY | Ubiquitously transcribed TPR gene on the Y chromosome |
| RBM | The RNA-binding motif on Y |
“Y Chromosomes” by Christinelmiller is licensed under CC BY-SA 4.0
MSY- Male-specific region of Y:
• This is the major portion of the Y chromosome
• It is made up of the euchromatin and heterochromatin regions,
• These are all collectively known as male-specific regions of Y.
• This region possesses genes for the traits such as – male gonadal development, spermatogenesis, and testis development.
• The euchromatin region has SRY, TDF and AZF like genes
• While the heterochromatin region contains around 5000 copies of tandemly repetitive sequences called SINES throughout the MSY region.
SRY gene:
• The SRY gene is located in the MSY ,on the p arm
• It is very important for the development of maleness.
• The SRY gene is the Sex-determining Region on Y,
• It has a single function exon which encodes a protein of approximately 204 amino acids.
• Structurally, the SRY gene is located within the specific region on the Y chromosome known as Testis determining region
• Scientists believe that the SRY gene might have evolved from the SOX gene of the X chromosome.
• The SRY gene is one of the most important genes in the pathway of male sex determination and differentiation, thus it is known as the ‘candidate gene’ in the gonadal development.
The early embryo has two systems of ducts,
• Namely the Wolffian and Müllerian ducts,
• These are capable of developing into the male and female reproductive tracts, respectively.
• The SRY gene product stimulates the indifferent gonad to develop into a testis.
• The testis then begins producing two hormones, testosterone and anti-Müllerian hormone, or AMH.
• Testosterone and one of its derivatives, dihydrotestosterone, induce formation of other organs in the male reproductive
system.
• While AMH causes the degeneration of the Müllerian duct.
• In females, who do not contain the SRY protein, the ovary forming pathway is activated by a different set of proteins.
• The fully developed ovary then produces estrogen
• Estrogen triggers development of the uterus, oviducts, and cervix from the Müllerian duct.
PAR:
• The PAR is known as a pseudoautosomal region
• It is located on extreme ends of Y chromosomes.
• The PAR on p arm is around 2.5Mb in size while the PAR on q arm is around 1Mb in size.
• The PAR has genes homologous to the X chromosomes that take part in the recombination during meiosis cell division.
• During the meiosis in males the PAR regions of X and Y combine and exchange genetic material.
• However, the rest of the regions of Y remain conserved
The AZF gene
• This gene is known as AZF- azoospermia factor.
• It is concerned with sperm formation.
• The AZF locus is comparatively larger in size than the SRY gene
• It is divided into three regions namely– AZFa, AZFb and AZFc.
• Mutation in the regions of AZF leads to failure in spermatogenesis.
• This condition is commonly known as azoospermia
ZFY gene
• This is another candidate gene,which is located on the Y chromosome,
• It encodes a zinc finger protein.
• It lies close to the pseudoautosomal boundary on the short arm of the human Y chromosome.
• In the mouse, Zfy was found to consist of two duplicated genes, Zfy-1 and Zfy-2, which are both present on the normal human Y chromosome.
Functions of Y chromosome
• Development of maleness
• Male gonadal differentiation and development
• Male sex determination
• Sperm cell development
• Testis development
• Development of other secondary male reproductive phenotypes
Inheritance pattern of Y chromosome:
- The Y chromosome follows a unique pattern of inheritance that is known as the Y-linked inheritance
- In this type of inheritance the genes on the Y chromosome transmit only from father to their male child only
- The inheritance pattern of the Y chromosome is widely useful for tracing the lineage of family.
- Genes located on Y chromosomes only inherited to male individuals and hence diseases or traits associated with the Y chromosome are thus inherited only in the males.
The X Chromosome
• The DNA of the X chromosome spans about 155 million base pairs
• It represents approximately 5 percent of the total DNA in cells.
• It represents about 800 protein-coding genes
• Each person normally has one pair of sex chromosomes in each cell.
• Females have two X chromosomes, while males have one X and one Y chromosome.
• During the embryonic development in females, one of the two X chromosomes is randomly and permanently inactivated in cells
other than egg cells.
• This phenomenon is called X-inactivation or Lyonization and creates a Barr body. Barr bodies are commonly used to determine
sex.
• Thus females, like males, have one functional copy of the X chromosome in each body cell.
• Because X-inactivation is random, in normal females the X chromosome inherited from the mother is active in some cells, and
the X chromosome inherited from the father is active in other cells
Some genes on the X chromosome escape X inactivation.
• The genes are located at the ends of each arm of the X chromosome is known as the pseudoautosomal regions escape inactivation.
• Genes in the pseudoautosomal regions are present on both sex chromosomes.
• As a result, men and women each have two functional copies of these genes.
• Many genes in the pseudoautosomal regions are essential for normal development
“X chromosome “ by No machine-readable author provided. The cat~commonswiki assumed (based on copyright claims). , via Wikimedia Commons is licensed under CC BY-SA 3.0
Diseases due to Changes in the structure or number of X chromosomes
For example, trisomy X syndrome is caused by the presence of three X chromosomes instead of two.
• Turner syndrome occurs when women inherit only one copy of the X chromosome.
• Some women have a rare super color vision trait called tetrachromacy, which is linked to the X chromosome.
• These women can see up to 100 million shades of color because they have four types of cone cells in their eye instead of the usual three
Functions of X chromosome
Many X chromosome genes, about one-fifth, appear to play a role in human cognition and brain development.
• Females are more immunoreactive than males and, although sex hormones have an important role in immune functions, the X chromosome is fundamental in shaping sex-specific immune responses.
• X-linked specific diseases usually affect only males, simply because they are hemizygous for X chromosome alleles.
Sex Determination
A sex-determination system is a biological system that determines the development of sexual characteristics in an organism.
• Most organisms that create their offspring using sexual reproduction have two sexes.
• Sex determination in animals is an integral part of reproduction.
• In general, sex determination describes the genetic and environmental processes that influence sex differentiation
Sex Determination in Mammals-XX/XY System
Primary sex determination is the determination of the gonads.
• In mammals, primary sex determination is strictly chromosomal and is not usually influenced by the environment.
• In most cases, the female is XX and the male is XY. Every individual must have at least one X chromosome.
• Since the female is XX, each of her eggs has a single X chromosome.
• The male, being XY, can generate two types of sperm: half bear the X chromosome, half the Y.
• If the egg receives another X chromosome from the sperm, the resulting individual is XX, forms ovaries, and is female;
• if the egg receives a Y chromosome from the sperm, the individual is XY, forms testes, and is male.
• The Y chromosome carries a gene that encodes a testis-determining factor.
• This factor organizes the gonad into a testis rather than an ovary.
• the mammalian Y chromosome is a crucial factor for determining sex in mammals.
• A person with five X chromosomes and one Y chromosome (XXXXXY) would be male.
• Furthermore, an individual with only a single X chromosome and no second X or Y (i.e., XO) develops as a female and begins making ovaries, although the ovarian follicles cannot be maintained. For a complete ovary, a second X chromosome is needed
XX-XOType
• This method of sex determination is seen in bugs, some insects such as cockroaches and grasshoppers.
• Thefemale with two X chromosomes are homogametic (XX)
• while the males with only one X chromosome are heterogametic (XO).
• Thepresence of an unpaired X chromosomes determines the male sex.
• The males with unpaired ‘X’ chromosome produce two types of sperms, one half with X chromosome and other half without X chromosome.
• The sex of the offspring depends upon the sperm that fertilizes the egg
ZO-ZZ Type
This method of sex determination is seen in certain moths, butterflies and
domestic chickens.
• In this type, the female possesses single ‘Z’ chromosome in its body cells and is heterogametic (ZO) producing two kinds of eggs some with ‘Z’ chromosome and some without ‘Z’ chromosome, while the male possesses two ‘Z’ chromosomes and is homogametic (ZZ)
ZW-ZZ type
This method of sex determination occurs in certain insects (gypsy moth) and
in vertebrates such as fishes, reptiles and birds.
• In this method the female has one ‘Z’ and one ‘W’ chromosome (ZW) producing two types of eggs, some carrying the Z chromosomes and some carry the W chromosome.
• The male sex has two ‘Z’ chromosomes and is homogametic (ZZ) producing a single type of sperm
“Avian sex determination” by CFCF via wikimedia commons is licensed under CC BY-SA 3.0
Test your Understanding