Chromosomal Differences: X and Y Chromosomes

• The evolutionary split between the X and Y chromosomes began roughly 200 million years ago.

Special Features of the Y Chromosome

• The Y chromosome contains the SRY gene which begins the development of male characteristics.
• The Sox3 gene is the corresponding gene on the X chromosome, but it is not involved in determining sex.

X Chromosome Inactivation

• In females, X inactivation evolved in order to avoid the harmful gene dosage effect.
• The inactivation of one of the X chromosomes is random.
• If a female has one X chromosome with a mutation for an X-linked disease, the other X chromosome might compensate, but if the normal X is inactivated, the disease might be expressed.
• Males only have one X chromosome so they do not experience this inactivation, or the gene dosage effect.

Chromosomal Differences

• Females have two X chromosomes; males have one X and one Y chromosome.
• The X chromosome is significantly larger than the Y chromosome, containing 900-1000 genes that are involved in essential cellular functions.
• The Y chromosome is much smaller, containing only 45-55 unique genes.
• Most of the X and Y chromosomes are non-homologous with the exception of two pseudoautosomal regions (PARs).
• Homologous chromosomes are similar in size, shape, and genetic content; the X and Y chromosomes are very different.
• The X chromosome contains over 1,000 genes involved in a wide variety of functions.
• The Y chromosome is much smaller and contains fewer genes.
• Despite the overall difference between the X and Y chromosomes, there are two regions on the X and Y chromosomes called pseudoautosomal regions (PARs).

Pseudoautosomal Regions (PAR)

• PAR1 and PAR2 are regions on the X and Y chromosomes where homologous recombination (crossing over) can occur during meiosis allowing for independent inheritance of genetic markers, despite the individual's chromosomal sex.
• These regions are found at the distal ends of the short and long arms of both chromosomes.
• Crossover in these regions help maintain genetic diversity in males.
• Pairing and crossing over during meiosis allows chromosomes to pair up with their homologous chromosome allowing for crossing over and increasing genetic diversity.
• PARs allow X and Y chromosomes to pair and undergo crossing over during meiosis.
• Without this pairing, it would be difficult for the chromosomes to segregate properly, potentially leading to problems like aneuploidy.

Y Chromosome Characteristics

• The Y chromosome is roughly 1/3 the size of the X chromosome.
• Despite its smaller size, the Y chromosome has a disproportionally important function in determining maleness.
• It contains both coding genes (which encode proteins involved in sexual differentiation) and non-coding regions, such as repetitive sequences and the pseudoautosomal regions.
• Non-coding DNA sequences may play roles in structural integrity and gene regulation.

Functional and Non-Functional Genes

• Many of the functional genes on the Y chromosome are involved in sexual differentiation, the formation of secondary sexual characteristics, and spermatogenesis, including SRY and DAZ.
• Non-functional genes may include sequences that are either vestigial or degraded.

Sexual Differentiation and the Y Chromosome

• The sex of the embryo is genetically determined at the time of fertilization.
• Morphological sexual characteristics do not develop until the seventh week after conception.
• The presence of the Y chromosome triggers male development, while the absence of a Y chromosome results in female development.

Testis Determining Factor (TDF) and the SRY Gene

• The Testis Determining Factor (TDF) was hypothesized to be the gene responsible for initiating male development and was eventually identified as the SRY gene.
• The SRY gene encodes a DNA binding protein that functions as a transcription factor, activating a cascade of genes.
• The SRY gene specifically triggers the differentiation of the gonads into testes; in the absence of SRY, the gonads default to ovaries.

SRY Gene Function

• The SRY gene encodes a protein that binds DNA and acts as a transcription factor, regulating the expression of other genes that are critical for male sexual differentiation.
• Presence of SRY results in male development.
• SRY is expressed in the genital ridges during embryonic development, just before the differentiation of the gonads into testes.
• The SRY gene begins a cascade that leads to the formation of the male reproductive system.