UNIT 9 – Sex Linked Inheritance (Q&A) | MZO-002 | MSCZOO | M.Sc. Zoology | IGNOU
SAQ 1
i) In the Protenor mode of the sex determination, males are
a) homogametic and have two sex chromosomes
b) heterogametic and have two sex chromosomes
c) homogametic and have one sex chromosome
d) heterogametic and have one sex chromosome
Answer: d) heterogametic and have one sex chromosome
ii) Female is heterogametic in
a) Humans
b) most birds
c) Drosophila
d) C. elegans
Answer: b) most birds
iii) Which of the following chromosomal mode of sex determination is exhibited by Drosophila?
a) XX/XO mode
b) XX/XY mode
c) ZZ/ZW mode
d) ZZ/ZO mode
Answer: b) XX/XY mode
iv) The sex in C. elegans are
a) males and females
b) males and hermaphrodites
c) Hermaphrodites only
d) Hermaphrodites and females
Answer: b) males and hermaphrodites
v) During self-fertilisation in hermaphrodites, ratio of sex in progenies is
a) 50% females and 50% male
b) 50% males and 50% hermaphrodites
c) All hermaphrodites
d) Majorly hermaphrodites, occasionally males
Answer: d) Majorly hermaphrodites, occasionally males
vi) In C. elegans, members are mostly
a) Females
b) Males
c) Hermaphrodites
d) Hermaphrodites and males (equal)
Answer: c) Hermaphrodites
vii) Which of the following chromosomal mode of sex determination is exhibited by humans?
a) XX/XY
b) XX/XO
c) ZZ/ZW
d) ZZ/ZO
Answer: a) XX/XY
viii) The sex-determining region in the Y chromosome has a master regulatory gene that encodes for a DNA-binding protein ................................... that is responsible for maleness in humans.
a) Testosterone
b) Dihydrotestosterones
c) Testis determining Factor
d) Anti-Mullerian hormone
Answer: c) Testis determining Factor
ix) In humans, which of the region in the Y chromosome share homology with X chromosome
a) PARS
b) SRY
c) MSY
d) Both a and b
Answer: a) PARS
x) The sex chromosomes in the karyotype are placed
a) based on shape and size like autosomes.
b) generally on the top
c) separately on the comer
d) generally placed in the centre
Answer: c) separately on the comer
xi) In Drosophila, the sex is determined by
a) Y chromosome
b) X chromosome
c) Ratio of X chromosomes to Y chromosome
d) Ratio of X chromosomes to the haploid set of autosomes
Answer: d) Ratio of X chromosomes to the haploid set of autosomes
xii) The sex of Drosophila with chromosome composition 3n, XXXY is
a) female
b) male
c) intersex
d) metafemale
Answer: a) female
xiii) XO Drosophila are generally
a) males and fertile
b) males and sterile
c) intersex
d) females
Answer: b) males and sterile
xiv) Drosophila with chromosome composition 4n, XXY has .............................. X/A ratio and is a ................................ .
a) 0.5, male
b) 1, female
c) 1, male
d) 0.5, female
Answer: a) 0.5, male
SAQ 2
Choose the appropriate option.
i) The mechanism of dosage compensation in Drosophila involves
a) Hyper-activation of single X in males
b) Hypoactivation of both X chromosomes in females
c) Inactivation of one of the X chromosomes in females
d) Hyper-activation of Y chromosomes in males
Answer: a) Hyper-activation of single X in males
ii) In females, sxl gene is expressed, it
a) suppress the expression of mle and msl genes which leads to dosage compensation.
b) activate the expression of mle and msl genes which leads to no dosage compensation.
c) suppress the expression of mle and msl genes which leads to no dosage compensation.
d) activate the expression of mle and msl genes which leads to dosage compensation.
Answer: c) suppress the expression of mle and msl genes which leads to no dosage compensation.
iii) Which one of the following phenomena is mainly responsible for X-chromosome inactivation in human females?
a) Increased XIST expression by inactive X chromosome
b) Increased XIST expression by active X chromosome
c) Increased TSIX by inactive X chromosome
d) Increased TSIX by active X chromosome
Answer: a) Increased XIST expression by inactive X chromosome
iv) The number of Barr in individuals with XXXY syndrome is
a) none
b) one
c) two
d) three
Answer: c) two
v) The Barr bodies are generally seen in
a) cytoplasm of female somatic cells
b) nuclei of female somatic cells
c) cytoplasm of male somatic cells
d) nuclei of male somatic cells
Answer: b) nuclei of female somatic cells
TERMINAL QUESTIONS
1. a) What is sex determination? Is it influenced by external factors?
What is sex determination?
Sex determination is the biological process by which an organism develops as a male or a female. It refers to the mechanism that decides the sexual identity of the individual. This determination can occur at the time of fertilization or later during embryonic development, depending on the species.
Sex determination governs the development of sex-specific structures like gonads (testes and ovaries), and controls the production of sex hormones, gametes and secondary sexual characteristics. The process is controlled either by genes or chromosomes (genetic factors) or by environmental conditions.
There are two main types of sex determination systems found in nature:
- Genetic Sex Determination (GSD)
- Environmental Sex Determination (ESD)
1. Genetic Sex Determiation (GSD)
In this system, the sex of an individual is fixed at the time of fertilization and is decided by the combination of sex chromosomes or specific genes. This system is most common in mammals, birds, insects and some plants. It includes the following types:
- XX-XY System: Found in humans and many mammals. XX individuals become females, XY individuals become males. The presence of the SRY (Sex-determining Region Y) gene on the Y chromosome is responsible for initiating male development.
- ZZ-ZW System: Found in birds, some reptiles, and butterflies. Males are ZZ, females are ZW. Here, it is the female who contributes the different sex chromosome.
- XO System: Found in grasshoppers and some insects. Females are XX, males are XO (only one X chromosome). Absence of the second X leads to male development.
- Haplo-Diploidy System: Found in bees, ants and wasps. Fertilized eggs (diploid) become females, while unfertilized eggs (haploid) become males.
In all these systems, genetic material (especially sex chromosomes) decides the sex and usually does not change after fertilization.
2. Environmental Sex Determination (ESD)
In some species, the environment plays a major role in deciding the sex of the offspring. This is called Environmental Sex Determination. It can happen in different ways:
- Temperature-Dependent Sex Determination (TSD): Found in many reptiles like turtles and crocodiles. The temperature at which the eggs are incubated determines whether the offspring will be male or female. For example, higher incubation temperature may produce females and lower temperature may produce males.
- Social Factors: In some fish like clownfish and wrasses, sex can change depending on the social structure. For example, if the dominant female dies, the dominant male may change into a female.
- Chemical Influence: In some cases, environmental chemicals can mimic hormones and affect the normal sex determination process.
So, sex determination can be either fixed by genetics or influenced by environmental factors, depending on the species.
Is Sex Determination Influenced by External Factors?
Yes, in many organisms, especially outside mammals and birds, sex determination is highly influenced by external environmental factors. This includes temperature, population structure and even chemicals present in the environment. These factors affect the regulation of gene expression and hormone levels during development, leading to male or female differentiation.
Here are some major ways external factors influence sex determination:
1. Temperature-dependent Sex Determination (TSD)
This is the most well-known example of ESD (Environmental Sex Determination), found in reptiles like turtles, lizards and crocodiles. The temperature affects gene expression in the gonads, especially genes like Aromatase, which converts androgens to estrogens, thus promoting female development. This mechanism shows that temperature-sensitive periods exist during embryonic development when a small change in temperature can alter the sex pathway.
Examples:
- In many turtles, low temperatures (below a threshold) during incubation produce males, while high temperatures produce females.
- In some crocodiles, intermediate temperatures result in females and both high and low extremes produce males.
2. Social and Behavioral Factors
In some species, especially fish, social environment plays a key role. This type of sex change is regulated by social signals or cues that influence the hormonal system, especially involving estrogens and androgens.
Examples:
- In clownfish, all individuals are born male. The most dominant male transforms into a female when the original female dies.
- In wrasses, the largest female can become a male in the absence of a dominant male.
3. Chemical Pollutants and Hormonal Disruptors
Certain environmental chemicals called endocrine-disrupting compounds (EDCs) can mimic or block natural hormones. These chemicals interfere with gene regulation, especially the hormonal balance required for proper gonad formation.
Example:
- In amphibians and fish, exposure to substances like pesticides (e.g., atrazine) or plastic-related compounds (like BPA) can lead to sex reversal or abnormal development of sex organs.
b) Differentiate between primary and secondary sex determination.
Sex determination is the process by which an organism develops as male or female. In most sexually reproducing eukaryotes, this process occurs in two distinct but interconnected stages: primary sex determination and secondary sex determination. Primary sex determination decides the type of gonad (testes or ovaries) that will develop, while secondary sex determination governs the development of external sexual characteristics under hormonal influence. These two processes work in sequence to establish complete sexual identity. Though both are part of sexual development, they are different in terms of mechanism, timing and outcomes.
There are the following major differences between primary and secondary sex determination:
1. Based on the Biological Role
Primary sex determination refers to the genetic decision that determines whether the bipotential gonads will become testes or ovaries. It plays a foundational role in defining the internal reproductive structure of the organism.
Secondary sex determination refers to the hormonal influence that leads to the development of external genitalia and secondary sexual traits such as breast development, facial hair, and body shape. It fine-tunes the visible and functional sexual identity.
2. Based on the Type of Regulation
Primary sex determination is based on genetic factors. It decides whether the bipotential gonads will become testes or ovaries. For example, in humans, if the SRY (Sex-determining Region Y) gene on the Y chromosome is present, the gonads develop into testes. If SRY is absent (as in XX), the gonads develop into ovaries.
Secondary sex determination is based on hormonal signals produced by the gonads and affects other sexual traits like external genitalia, voice pitch and body structure. For example, In human males, testes produce testosterone, which leads to development of penis and scrotum. In females, ovaries produce estrogen, leading to development of breasts and wider hips.
3. Based on the Timing During Development
Primary sex determination occurs early in embryogenesis, during the stage when gonads are still undifferentiated.
Secondary sex determination begins after the gonads have formed, and its effects continue into later fetal stages and puberty, when secondary sexual characteristics become fully visible.
4. Based on the Structures Affected
Primary sex determination affects only the gonadal development forming either testes or ovaries.
Secondary sex determination influences non-gonadal tissues, such as skin, muscles, skeletal structure and behavior patterns associated with male or female identity.
5. Based on Reversibility and Stability
Primary sex determination is usually irreversible under natural conditions. Once a gonad develops into a testis or ovary, it does not revert.
Secondary sex determination may show some flexibility. In certain animals or under experimental conditions, hormonal manipulation can lead to changes in secondary sexual traits even after development.
c) How sex is determined in Drosophila? Explain.
In Drosophila, sex is not determined by the presence or absence of a Y chromosome, as seen in humans. Instead, it is decided by a system known as the Genic Balance Mechanism, which depends on the ratio of X chromosomes to sets of autosomes (X:A ratio). This system was proposed by Calvin Bridges in 1925 based on his experiments in Drosophila.
Sex determination in Drosophila can be best explained by understanding it under two major aspects:
I. X:A Ratio Principle
This principle states that the sexual phenotype of the organism is determined by the ratio of X chromosomes to the number of haploid sets of autosomes (A).
- Ratio = 1.0 (2X:2A) → Normal Female
- Ratio = 0.5 (1X:2A) → Normal Male
- Ratio > 1.0 (e.g., 3X:2A) → Metafemale (sterile)
- Ratio < 0.5 (e.g., 1X:3A) → Metamale (sterile)
- Intermediate ratio (e.g., 2X:3A = 0.67) → Intersex (both male and female traits)
In this system, the Y chromosome does not determine maleness. It is only essential for spermatogenesis, so XO flies are male but sterile.
II. Molecular Basis of Sex Determination
While the chromosomal ratio sets the initial signal, the actual development into male or female is controlled by a gene regulatory cascade. This includes the following key genes:
- Sex-lethal (Sxl): Acts as the master switch.
- Active in females → turns ON downstream genes
- Inactive in males → default pathway proceeds
- Transformer (tra): Activated by Sxl in females through alternative splicing.
- Doublesex (dsx) and fruitless (fru): Final genes in the cascade that control the formation of sex-specific structures and behavior.
So:
- In females (X:A = 1.0) → Sxl ON → tra functional → female-specific splicing of dsx and fru → Female phenotype
- In males (X:A = 0.5) → Sxl OFF → tra non-functional → male-specific splicing of dsx and fru → Male phenotype
This regulatory cascade is initiated during the early embryonic stage, and once set, the sexual fate becomes irreversible.
2. What is dosage compensation? What are the different mechanisms of dosage compensation?
Dosage compensation is a genetic mechanism that balances the expression of X-linked genes between sexes in species where the number of X chromosomes differs between males and females. In many animals, such as humans and fruit flies, females have two X chromosomes (XX) while males have only one (XY or XO). Without dosage compensation, females would produce twice the amount of X-linked gene products compared to males, which could disturb normal cellular functions. This mechanism ensures that both sexes produce similar levels of X-linked gene products, maintaining gene expression balance across the genome.
Why Dosage Compensation Is Necessary?
- Gene expression must be kept in a balanced ratio for normal cell and organismal function. Unequal expression of X-linked genes could lead to serious developmental and physiological defects. Dosage compensation ensures that the expression of genes from the X chromosome is properly regulated, regardless of how many X chromosomes are present. It corrects the imbalance between the sexes and also maintains coordination between autosomal and sex-linked gene expression.
Mechanisms of Dosage Compensation
There are three main mechanisms of dosage compensation observed in different organisms. Each mechanism deals with the expression difference of X chromosomes in its own way:
1. X-Chromosome Inactivation in Mammals
In mammals like humans and mice, females have two X chromosomes, while males have one. To equalize gene expression, one of the two X chromosomes in females is inactivated early during embryonic development. This process is random, meaning either the maternal or paternal X can be inactivated in a given cell.
This inactivation is controlled by the XIST gene (X-inactive specific transcript) located on the X chromosome. The XIST RNA coats the chromosome from which it is transcribed and causes it to become condensed into a structure called a Barr body, rendering it largely transcriptionally inactive.
This mechanism is known as the Lyon Hypothesis, proposed by Mary Lyon in 1961. Although most of the genes on the inactive X are silenced, a few genes escape inactivation and are expressed from both X chromosomes.
2. Hyperactivation of Single X in Males – Drosophila
In the fruit fly Drosophila melanogaster, males have only one X chromosome, but unlike mammals, this X is not inactivated. Instead, the expression of genes on the male's single X chromosome is doubled, so that it matches the combined output of the two X chromosomes in females.
This hyperactivation is controlled by the Male-Specific Lethal (MSL) complex, which binds to the male X chromosome and increases transcriptional activity. Along with the MSL complex, non-coding RNAs such as roX1 and roX2 are also involved in targeting the complex to the X chromosome.
Thus, in Drosophila, dosage compensation is achieved by boosting the expression of genes on the male's only X chromosome.
3. Hypoactivation of Both X Chromosomes – C. elegans
In the nematode worm Caenorhabditis elegans, there are two sexes: hermaphrodites (XX) and males (XO). In this system, dosage compensation occurs by reducing the expression of genes from both X chromosomes in hermaphrodites by half. This results in a total expression level equivalent to the single X chromosome in males.
This downregulation is controlled by a dosage compensation complex (DCC), which is similar to the condensin complex and binds specifically to both X chromosomes in hermaphrodites. As a result, X-linked gene expression is equalized between the sexes.
Note:
Other Examples (Incomplete Compensation)
In some organisms like birds (with ZW sex-determination) and butterflies, dosage compensation is either incomplete or absent. For example, in birds, males are ZZ and females are ZW and there is often higher expression of Z-linked genes in males compared to females, showing that not all species use complete dosage compensation.
3. State the reason for the following:
a) Calico cats are generally female.
Calico refers to cats with three distinct fur colors white, black, and orange in separate patches. This pattern occurs mostly in females due to X-linked gene expression.
Calico cats are known for their beautiful tri-color fur pattern which includes orange, black and white patches. This pattern is not just a matter of fur color but is directly linked to genetics, specifically to a gene located on the X chromosome that controls coat color in cats. The gene responsible for coat color has two main alleles:
- Xᴼ – codes for orange fur
- Xᵇ – codes for black fur
The white fur patches are controlled by another gene unrelated to the sex chromosome, so the main focus for the calico pattern is on the orange and black colors.
For a cat to appear calico, it must carry both orange (Xᴼ) and black (Xᴮ) alleles together. This combination can only occur if the cat has two X chromosomes, which is the case in female cats (XX). Male cats usually have only one X and one Y chromosome (XY), so they can carry either Xᴼ or Xᴮ, but not both at the same time, which makes them either black or orange, but not calico.
Now in females (XX), both X chromosomes are present but only one X chromosome is active in each cell due to a natural process called X-chromosome inactivation, also known as Lyonization. This process was first proposed by geneticist Mary Lyon in 1961. She suggested that in some cells, the Xᴼ allele is active (producing orange fur) and in other cells, the Xᴮ allele is active (producing black fur). This creates a mosaic-like pattern of orange and black patches on the cat's fur. The presence of white patches is due to a different gene that controls the distribution of color.
Since X-inactivation happens randomly in each cell during early development, it results in the unique calico appearance. Each calico cat is genetically and physically unique because of this randomness.
In very rare cases, a male cat can be calico, but only if he has an extra X chromosome, making his genotype XXY instead of the usual XY. This can happen due to a chromosomal abnormality similar to Klinefelter's syndrome in humans. These rare male calico cats can have both Xᴼ and Xᴮ alleles, and X-inactivation can occur, leading to a calico pattern. However, such males are almost always infertile due to the chromosomal imbalance.
So, the calico pattern is directly dependent on the presence of two different X chromosomes with different coat color alleles and on the process of random X-chromosome inactivation, both of which are normally present only in female cats. This is why calico cats are generally female.
b) The Y chromosome does not play an important role in sex determination in Drosophila.
The Y chromosome does not play an important role in sex determination in Drosophila melanogaster because the sex of the organism is not decided by the presence or absence of the Y chromosome. Instead, sex determination in Drosophila is based on the ratio of X chromosomes to sets of autosomes, known as the X:A ratio. This is very different from the mechanism used in humans and other mammals, where the presence of a Y chromosome [specifically the SRY (Sex-determining Region Y) gene)] triggers male development.
In Drosophila, the normal diploid number of chromosomes includes two sex chromosomes (either XX or XY) and two sets of autosomes (2A). The X:A ratio is calculated by comparing the number of X chromosomes to the number of sets of autosomes.
There are the following basic possibilities:
- X:A = 1.0 (e.g., XX with 2A)
- This ratio results in female development. The two X chromosomes activate certain key genes that lead to the female pathway.
- X:A = 0.5 (e.g., XY with 2A or XO with 2A)
- This ratio results in male development. The presence of only one X chromosome is not enough to activate female-specific genes, so the male pathway is followed.
- X:A = 1.5 (e.g., XXX with 2A)
- This gives a metafemale, which is usually sterile and shows abnormal development.
- X:A = 0.67 or other intermediate ratios
- These lead to intersex conditions, where the organism shows both male and female characteristics.
The Y chromosome in Drosophila is not involved in determining maleness. Instead, it carries genes that are important for male fertility. Males with the genotype XO (one X and no Y) are still male, but they are sterile. This shows that the Y chromosome is not necessary for male development, but it is essential for producing functional sperm.
Thus, in Drosophila, sex determination depends mainly on the number of X chromosomes in relation to autosomes. The Y chromosome does not play a primary role in this process. Its main role is in ensuring fertility in males, not determining their sexual development.
c) Klinefelter syndrome individuals (47, XXY) inactivate one of the X-chromosomes but still, they are not normal males.
Normally, a human male has 46 chromosomes, which include 44 autosomes and one pair of sex chromosomes (XY). Similarly, a normal female also has 46 chromosomes, with 44 autosomes and XX sex chromosomes. But Klinefelter syndrome is a chromosomal disorder where individuals have an extra X chromosome. Their chromosome constitution is 47 chromosomes, written as 44 autosomes + XXY sex chromosomes. This means they have one Y chromosome, which makes them genetically male, but also two X chromosomes instead of the usual one. This additional X chromosome creates an imbalance in sex chromosome dosage that disrupts normal male development.
In each cell of individuals with more than one X chromosome, one of the X chromosomes becomes inactivated. This process is called X-chromosome inactivation (XCI) and it happens to equalize the dosage of X-linked genes between males and females. The inactivated X forms a structure called a Barr body. So in Klinefelter individuals, one of the two X chromosomes is inactivated, just like in normal females.
However, even after this X-inactivation, individuals with Klinefelter syndrome are not completely normal males because of the following reasons:
- Incomplete inactivation of the X chromosome
- X-inactivation is not perfect. About 15% of genes on the inactivated X chromosome escape inactivation, especially those located in the pseudoautosomal regions (PARs). These genes are still expressed from both X chromosomes. This results in overexpression of some X-linked genes, which leads to abnormal gene dosage and affects development.
- Hormonal imbalance
- The extra X chromosome affects the function of the testes, leading to lower levels of testosterone, the main male sex hormone. As a result, these individuals often show feminized secondary sexual characteristics, such as reduced facial and body hair, gynecomastia (enlarged breast tissue) and poor muscle development.
- Infertility
- Due to abnormal testicular development, sperm production is very low or absent in most Klinefelter individuals. The presence of the extra X interferes with meiosis and proper germ cell development, leading to infertility.
- Cognitive and developmental issues
- Many individuals with Klinefelter syndrome also experience mild learning disabilities, language development delays, or problems with attention and executive function. These symptoms vary in severity but are likely linked to abnormal gene expression from the extra X chromosome.
So, while X-inactivation occurs and helps reduce the effect of having an extra X chromosome, it does not completely eliminate the abnormal gene dosage. Therefore, individuals with Klinefelter syndrome still show noticeable symptoms and differ from normal males.
d) Environment plays an important role in sex determination.
In many organisms, sex is not fixed by chromosomes alone. Instead, environmental factors play a key role in deciding whether an individual will develop as male or female. This is called Environmental Sex Determination (ESD). This system is especially common in reptiles, some fish and certain invertebrates. The environment affects the expression of specific genes and hormones that control the development of testes or ovaries.
There are the following main reasons why environment plays such an important role in sex determination:
- Temperature affects gene expression and hormone activity
- In many reptiles like turtles, alligators and lizards, the temperature during a particular stage of embryonic development decides the sex of the offspring. This is called Temperature-Dependent Sex Determination (TSD). For example, in many turtles, lower temperatures produce males and higher temperatures produce females. The temperature influences enzymes like aromatase, which converts male hormones (androgens) into female hormones (estrogens). So, the temperature indirectly controls which type of gonad will form.
- Social environment triggers hormonal changes
- In some fish like clownfish and wrasses, sex is not fixed from birth. If the dominant female dies, a male may change into a female. This is called sequential hermaphroditism, where the organism changes sex during its lifetime. The social signals and hierarchy within the group lead to internal hormonal changes that result in sex reversal. This helps maintain a balanced sex ratio for better reproductive success.
- Chemical environment can interfere with normal development
- Pollutants and chemicals in the environment, especially endocrine-disrupting substances, can interfere with normal hormonal pathways. These chemicals can mimic or block hormones and cause abnormal sex development. In some amphibians and fish, exposure to such pollutants results in intersex conditions, where both male and female characteristics appear. This shows that chemical environment can override genetic instructions.
Thus, environment plays an important role in sex determination because it directly influences genetic pathways, hormone production and developmental signals. It allows organisms to adapt their sex ratios according to surroundings, which can be helpful for population survival in changing conditions.
e) The sxl gene also determines dosage compensation in Drosophila
In Drosophila melanogaster, the sxl (Sex-lethal) gene plays a dual role. First, it acts as a master regulator of sex determination. Second, it also controls dosage compensation, which is the process by which organisms equalize the expression of X-linked genes between males (XY) and females (XX). In Drosophila, males have one X chromosome and females have two X Chromosomes. To balance this, males upregulate their single X chromosome. The sxl gene ensures this balance happens only in the correct sex.
The sxl gene also determines dosage compensation in Drosophila because it works as a molecular switch. It links sex determination and gene expression regulation by controlling the activity of the MSL complex based on the organism's chromosomal sex.
There are two main reasons why the sxl gene also determines dosage compensation:
1. The sxl gene regulates the activation of the Male-Specific Lethal (MSL) complex
In Drosophila, dosage compensation is carried out by a group of proteins and RNAs known as the MSL complex. This complex binds to the male X chromosome and increases its transcription by modifying the chromatin. However, this system must only be active in males. If it gets activated in females, it causes overexpression of X-linked genes, which is lethal.
The sxl gene prevents this from happening. In females, the sxl gene is active. It produces a functional SXL protein. This protein inhibits the translation of the msl-2 mRNA, which is necessary for the formation of the MSL complex. Without MSL complex formation, the X chromosome in females is not upregulated. This prevents lethal gene overexpression. Therefore, the sxl gene maintains dosage balance by blocking the dosage compensation machinery in females.
2. The sxl gene is turned on only in females due to X:A ratio, linking it directly to both sex determination and dosage compensation
The sxl gene is activated only in individuals with an X:A ratio of 1.0, which is found in XX females. In males (X:A = 0.5), the gene is not activated and no functional SXL protein is produced. As a result, msl-2 is translated freely, leading to MSL complex formation and upregulation of the single X chromosome in males.
This makes the sxl gene a central switch. When sxl is active in females, it both determines female sexual development and prevents dosage compensation. When inactive in males, it allows dosage compensation to proceed.
4. Humans and Drosophila have XX/XY mode of sex determination. How is the sex determination process in humans different from Drosophila?
Both humans and Drosophila melanogaster use the XX/XY chromosomal system of sex determination. This means in both species, females have two X chromosomes (XX). However, the way in which sex is actually determined in both organisms is very different. In humans, it is based on the presence of the Y chromosome, while in Drosophila, it depends on the ratio of X chromosomes to sets of autosomes, which is called the X:A ratio.
Sex Determination in Humans
In humans, the presence or absence of the Y chromosome is the key factor in sex determination. The Y chromosome carries a gene called SRY (Sex-determining Region Y), which is responsible for initiating male development. If the SRY gene is present, the undifferentiated gonads develop into testes. These testes then produce testosterone, which leads to the development of male secondary sexual characteristics. If the SRY gene is absent, the gonads develop into ovaries and the individual becomes female.
So, in humans:
- XY = male, because of the presence of the SRY gene on the Y chromosome.
- XX = female, due to absence of the Y chromosome and thus SRY.
Note- Even if more than one X chromosome is present (like in Klinefelter syndrome, XXY), the presence of Y usually leads to male development, though with abnormalities.
Sex Determination in Drosophila
In Drosophila, sex is not determined by the presence of a Y chromosome. Instead, it is based on the ratio of X chromosomes to the number of sets of autosomes, called the X:A ratio. Every Drosophila has two sets of autosomes (2A), so the sex is determined by how many X chromosomes are present relative to these autosomes.
This ratio directly controls the activity of a master regulatory gene called Sex-lethal (sxl). When the X:A ratio is 1.0 (for example, XX/2A), the sxl gene is activated and this triggers the female-specific gene expression pathway, leading to female development. When the X:A ratio is 0.5 (for example, XY/2A or XO/2A), the sxl gene is not activated and the default gene expression pathway leads to male development. Therefore, sex is determined by whether the sxl gene is turned on or off and this in turn is strictly controlled by the X:A ratio.
Other combinations of X:A ratio also lead to specific outcomes:
- X:A between 0.5 and 1.0 results in intersex individuals (with mixed male and female characteristics)
- X:A > 1.0 produces metafemales (usually sterile and abnormal)
- X:A < 0.5 produces metamales (also sterile and abnormal)
Although males in Drosophila have a Y chromosome, it does not determine sex. Its role is limited to spermatogenesis, meaning it is required for male fertility, but not for deciding whether the individual is male.
5. What is Lyon's hypothesis?
Lyon's hypothesis, also called the Lyonization hypothesis, was first proposed by Mary F. Lyon in 1961. This hypothesis was developed to explain the mechanism behind dosage compensation in mammalian females. In humans and other mammals, females have two X chromosomes (XX), while males have only one X chromosome (XY). If both X chromosomes in females remained fully active, they would produce twice the amount of X-linked gene products compared to males, which would create a serious genetic imbalance. To solve this problem, nature has evolved a system where one of the two X chromosomes in females becomes inactive in each somatic cell. This balancing mechanism is known as X-inactivation.
According to Lyon's hypothesis, during the early stages of embryonic development, each somatic cell in a female randomly inactivates one of the two X chromosomes. This means that in some cells, the maternal X chromosome becomes inactive, while in others, the paternal X chromosome is silenced. This random inactivation process ensures that there is no consistent dominance of either the maternal or paternal X across all cells. Once an X chromosome is inactivated in a particular cell, all its daughter cells inherit the same inactive X chromosome, making this process clonal and stable throughout the lifetime of the organism.
The inactivated X chromosome condenses into a compact and heterochromatic structure known as the Barr body, which is visible during the interphase stage of the cell cycle under a microscope. This inactivated X chromosome becomes largely transcriptionally silent, meaning that most of its genes are not expressed. However, it is important to note that some genes located in pseudoautosomal regions of the X chromosome may escape inactivation and continue to be expressed.
Lyon's hypothesis is also important in understanding sex chromosome aneuploidies like Turner syndrome (45, X) and Klinefelter syndrome (47, XXY). In Turner syndrome, there is only one X chromosome and no inactivation occurs. In Klinefelter syndrome, even though one X chromosome is inactivated, the presence of an extra X chromosome still affects development, as some genes escape inactivation and lead to phenotypic abnormalities.
Key points of Lyon's Hypothesis:
- X-inactivation is random and occurs in early embryonic development.
- Only one X chromosome remains active per somatic cell in females.
- The inactive X chromosome appears as a Barr body.
- Inactivation is stable and clonal in the descendant cells.
- Some genes escape inactivation, especially in pseudoautosomal regions.
Example:
A well-known example of Lyon's hypothesis can be seen in tortoiseshell or calico cats, where different patches of fur show different colors due to X-inactivation. These cats are mostly female and display mosaicism as some cells express the allele from one X chromosome, while others express the allele from the other X.
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