Genetic Mechanisms of Sex Determination: Chromosomes, Syndromes, and Environmental Factors
Genetic Mechanisms of Sex Determination
Meiosis ensures the genetic constancy of a species.
Heteromorphic Chromosomes and Sexual Differentiation
Heteromorphic chromosomes are dissimilar chromosomes, such as the XY pair in mammals. They characterize one sex or the other in many species. While some sex determination is decided by genes on these sex chromosomes, others are located on autosomes.
Life Cycles and Sexual Dimorphism
Life cycles depend on sexual differentiation. Sexual dimorphism refers to the observable differences between males and females.
- Primary sexual differentiation in multicellular organisms involves only the gonads, where gametes are produced.
- Secondary sexual differentiation involves the overall appearance of the organism.
Organisms can be classified by their reproductive organs:
- Unisexual (dioecious or gonochoric): Possessing only male or female reproductive organs.
- Bisexual (monoecious or hermaphroditic): Possessing both male and female reproductive organs, capable of producing both gametes.
Sex Determination in Chlamydomonas
Chlamydomonas, a green alga, exhibits infrequent periods of sexual reproduction. Most of its life cycle is spent in the haploid, asexually reproducing (vegetative) phase. During adverse nutrient conditions (e.g., low nitrogen), daughter cells act as gametes. These daughter cells join together in fertilization (forming isogametes), creating a diploid zygote that can withstand harsh environmental conditions. Once conditions improve, meiosis ensues, and haploid vegetative cells are produced again.
Chlamydomonas is considered isogamous because it produces isogametes, which are not visually distinguishable from one another. However, there are two biochemically distinct mating types: Mt+ and Mt-. The ‘plus’ type mates only with the ‘minus’ type and vice versa. After fertilization and fusion, meiosis produces four haploid cells (zoospores), typically with two (+) types and two (-) types.
Sex Determination in Zea mays (Maize)
Maize (corn) is a monoecious plant, meaning it has both male and female structures on the same individual. Sex determination occurs differently in various tissues.
Male Structures: Stamens
On the sporophyte, stamens (male reproductive organs) collectively make up the tassel. They produce diploid microspore mother cells, each undergoing meiosis to give rise to four haploid microspores. Each haploid microspore then develops into a mature male microgametophyte (pollen grain) containing two haploid sperm nuclei.
Female Structures: Pistil
The pistil (female reproductive organ) contains female diploid cells (megaspore mother cells). After meiosis, only one of the four haploid megaspores survives. This surviving megaspore divides mitotically three times, forming eight haploid nuclei within the embryo sac. Two nuclei unite near the center, forming the endosperm nuclei. One becomes the oocyte nucleus, and two synergids are located at the micropyle end of the sac, where sperm enters. The last three nuclei cluster at the opposite end of the sac, forming antipodal nuclei.
Pollination Process
- Pollen grains make contact with the stigma (silks) of the pistil.
- They develop long pollen tubes that grow toward the embryo sac.
- Upon contacting the micropyle, two sperm nuclei enter the embryo sac.
- One sperm nucleus unites with the haploid oocyte nucleus, and the other unites with the two endosperm nuclei. This process is known as double fertilization.
- Double fertilization creates a diploid zygote nucleus and a triploid endosperm nucleus.
- A single corn cob can have thousands of these, each forming a kernel. Each kernel, if it germinates, gives rise to a new sporophyte plant.
Sex Determination in Caenorhabditis elegans
Caenorhabditis elegans, a nematode, has 959 somatic cells and two sexual phenotypes:
- Males: Possess only testes.
- Hermaphrodites: Possess two gonads, producing both eggs and sperm.
Hermaphrodites primarily self-fertilize, resulting in approximately 99% hermaphrodites and less than 1% males. However, if hermaphrodites are crossed with males, the offspring ratio is roughly 50% hermaphrodites and 50% males.
C. elegans lacks a Y chromosome. Hermaphrodites have two X chromosomes, resulting in a 1.0 ratio of X chromosomes to autosomes. Males have one X chromosome, leading to a 0.5 ratio of X chromosomes to autosomes.
Protenor Mode of Sex Determination (XX/XO)
Exhibited by organisms like butterflies, this mode results in a 1:1 sex ratio that depends on the random distribution of the X chromosome into half of the male gametes. C. elegans also exhibits this system.
Lygaeus Mode of Sex Determination (XX/XY)
Observed in organisms such as the milkweed bug, this mode involves a Y chromosome, which is typically smaller and heterochromatic. It also results in a 1:1 sex ratio.
Heterogametic and Homogametic Sexes
- Heterogametic sex: Produces unlike gametes (e.g., males of Protenor and Lygaeus, producing X and O or X and Y gametes). In certain moths, butterflies, fish, reptiles, amphibians, one plant species, and most birds, the female is heterogametic (ZZ/ZW system, where females are ZW and males are ZZ).
- Homogametic sex: Produces like, uniform gametes with regard to chromosome numbers and types (e.g., females of Protenor and Lygaeus, producing only X-bearing gametes).
The Y Chromosome and Human Male Development
The Y chromosome plays a crucial role in determining maleness in humans. While XX individuals are female and XY individuals are male, how do we know the Y chromosome causes maleness, rather than the absence of a second X chromosome?
Sex Chromosome Abnormalities and Their Impact
Studies of individuals with sex chromosome abnormalities provide insight into the Y chromosome’s role.
Klinefelter Syndrome (47, XXY)
Occurring in approximately 1 in 660 male births, individuals with Klinefelter syndrome are phenotypically male but often tall with long legs and arms. They have underdeveloped testes and prostate glands, lack facial hair, are infertile, and may exhibit slight gynecomastia. They are sometimes slow learners. This syndrome can involve more than one X chromosome (e.g., 47, XXY; 48, XXXY; 49, XXXXY).
Turner Syndrome (45, X)
Affecting approximately 1 in 2000 female births (the number is lower because most affected fetuses die in utero), individuals with Turner syndrome are phenotypically female. They are typically short, may have malformed features such as a webbed neck, high palate, small jaw, congenital heart and kidney defects, and ovarian failure, leading to infertility. Learning disabilities are also common. This condition, 45, XO, can result in individuals called mosaics, where somatic cells have two different genetic cell lines, each with a different karyotype (e.g., 45,X/46,XY or 45,X/46,XX).
Both Klinefelter and Turner syndromes are caused by nondisjunction, the failure of X chromosomes to segregate properly during meiosis. Cases of individuals with only a Y chromosome (45,Y) are not observed because they are not viable.
47, XXX Syndrome (Triplo-X)
Occurring in approximately 1 in 1000 female births, many individuals with triplo-X syndrome are perfectly normal. Some may have underdeveloped sex characteristics, sterility, and mental retardation. More severe forms include 48, XXXX and 49, XXXXX syndromes.
47, XYY Condition (Jacobs Syndrome)
Males with Jacobs syndrome are often over 6 feet tall and may have subnormal intelligence. A higher percentage of individuals with this condition are found in mental and penal institutions.
XXXX Syndrome (Tetrasomy X)
Also known as 48, XXXX, this condition is found only in females (no Y chromosome present). Approximately 100 cases are known worldwide.
XXXXX Syndrome (Pentasomy X)
With only about 25 known cases worldwide, individuals with pentasomy X exhibit mental, growth, and motor retardation.
Human Sexual Differentiation
Every human embryo is initially hermaphroditic. By the fifth week of gestation, gonadal ridges form alongside the kidneys, remaining sexually indifferent. These are bipotential glands, capable of developing into either male (testes) or female (ovaries) gonads. Primordial germ cells migrate to these ridges. The outer cortex has the potential to become an ovary, while the inner medulla has the potential to become a testis. Similarly, the Wolffian duct has the potential to form male reproductive organs, and the Mullerian duct has the potential to form female reproductive organs.
The presence or absence of the Y chromosome triggers gonadal development:
- In an XY constitution, the medulla develops into testes.
- In the absence of a Y chromosome (XX constitution), the cortex forms ovarian tissue.
As either the male or female duct system develops, the other degenerates. The Mullerian duct forms the oviducts (fallopian tubes), uterus, cervix, and parts of the vagina.
The Y Chromosome and Male Development
The Y chromosome contains at least 75 genes, compared to the 900-1400 genes on the X chromosome. Some Y-linked genes have homologous counterparts on the X, while others do not.
Key Regions of the Y Chromosome
- Pseudoautosomal regions (PARs): Located on both ends of the Y chromosome, these regions share homology with regions on the X chromosome. They synapse and recombine with the X during meiosis (unlike the majority of the Y chromosome). PARs are critical for X and Y segregation during male gametogenesis.
- Male-specific region of the Y (MSY): This 95% of the Y chromosome does not synapse and recombine with the X chromosome. Some parts share homology with genes on the X chromosome, while others do not. The MSY contains both euchromatic regions (functional genes) and heterochromatic regions (lacking genes).
- Sex-determining region Y (SRY): Located within the euchromatin of the MSY, this gene controls male sexual development. It is active in XY embryos at 6-8 weeks of gestation. The SRY gene encodes the protein testis-determining factor (TDF), which causes undifferentiated gonadal tissue to form testes. TDF is a transcription factor—a DNA-binding protein that interacts directly with regulatory sequences of other genes to stimulate their expression. It also activates Mullerian Inhibiting Substance (MIS), which causes the regression of the Mullerian duct. Notably, there are men with an XX karyotype who possess the SRY gene, and women with an XY karyotype who lack the SRY gene.
Human Sex Ratios
The ratio of males to females in humans is not 1.0.
- Primary sex ratio: Reflects the proportion of males to females conceived in a population.
- Secondary sex ratio: Reflects the proportion of each sex that is born. This is easier to determine but does not account for embryonic and fetal mortality.
For example, the secondary sex ratio in the Caucasian population of the United States is approximately 1.06 (106 males to 100 females), in the African American population of the United States it is 1.025, and in Korea it is 1.15.
While males produce an equal number of X and Y-bearing sperm, and each sperm is generally assumed to have equal viability and motility in the female reproductive tract, and the egg surface is equally receptive to both types of sperm, it is possible that the smaller Y chromosome makes male sperm more motile, contributing to these observed ratios.
Dosage Compensation of X-Linked Genes in Mammals
Females have two X chromosomes, while males have only one. This disparity could create a ‘genetic dosage’ difference between the two sexes, leading to attendant problems for all X-linked genes, such as the production of twice as much product from X-linked genes in females.
Balancing Gene Expression
Dosage compensation is a mechanism that balances the dose of X chromosome gene expression in females and males.
Barr Bodies
A Barr body, or ‘sex chromatin body,’ is an inactivated X chromosome. Evidence for this comes from studies of sex chromosome syndromes. Regardless of how many X chromosomes are present, all but one are inactivated and appear as Barr bodies. This follows the ‘N-1’ rule, where N is the total number of X chromosomes.
The Lyon Hypothesis
The Lyon Hypothesis addresses which X chromosome is inactivated in females (maternal, paternal, or random). Early in embryonic development, inactivation of one X chromosome occurs randomly in somatic cells. All descendant cells then have the same X chromosome inactivated as their initial progenitor cell. This explains why female cats can have patches of different fur colors (calico or tortoiseshell mosaics), while males typically do not (males receive their single X from their mother only).
Learn more about calico cat genetics
Lyonization, the inactivation of an X chromosome into a Barr body, means that mammalian females are mosaics for all heterozygous X-linked alleles. Some areas of the body express only maternally derived alleles, and some express only paternally derived alleles. Examples include red-green color blindness (an X-linked recessive disorder where males are fully colorblind, but females may have patches of defective color perception) and anhidrotic ectodermal dysplasia.
Mechanism of X Inactivation
The X inactivation center (Xic), located on the proximal end of the p-arm of the X chromosome in humans, is critical for this process. It is genetically expressed only on the inactivated X chromosome and spans approximately 1 Mb (10^6 base pairs). The Xic contains several putative regulatory units and four genes, including the X-inactive specific transcript (XIST) gene, which is critical for X inactivation. Two other noncoding genes at the Xic locus, Tsix and Xite, also play important roles in X inactivation.
Sex Determination in Drosophila
In Drosophila (fruit flies), the Y chromosome does not cause maleness. Instead, the ratio of X chromosomes to autosomal sets plays a critical role in sex determination. A ratio of 1.0 results in females, while a ratio of 0.5 results in males. This mode of sex determination is explained by the genic balance theory. Dosage compensation in Drosophila involves male X-linked genes being transcribed at twice the level of comparable genes in females.
Temperature-Dependent Sex Determination in Reptiles
Unlike genotypic sex determination (GSD), where sex is determined genetically, many reptiles exhibit temperature-dependent sex determination (TSD). This includes crocodiles, most turtles, and some lizards. In these species, sex is determined by the incubation temperature of eggs during a critical period of embryonic development. There are specific female-determining temperatures (FT) and male-determining temperatures (MT).