Sex Chromosomes and Sex Linkage

Sex Chromosomes and Sex Determination

• In the late 19th and early 20th centuries, the difference in chromosome constitutions between males and females was noted, leading to the identification of sex chromosomes as sex-determining.
• The XY sex-determining system evolved independently from the ZW sex-determining system.
• Thomas Hunt Morgan mapped the first sex-linked trait (the white locus for eye color) to the X chromosome in Drosophila melanogaster and determined the genetics of sex in flies.

The Mammalian Y Chromosome and Sex Determination

• The Y chromosome is smaller than the X chromosome and is gene-poor.
• Small regions at the tips of the Y chromosome are homologous with the X chromosome, known as pseudoautosomal regions (PAR), which allow the X and Y chromosomes to pair and recombine during meiosis in the male.
• The gene SRY (Sex-determining Region Y gene) is necessary and sufficient to cause male development, encoding a transcription factor that activates a testis-forming pathway early in development.
• SRY is necessary for spermatogenesis, but other genes on the Y chromosome are also required.

X-Linked Traits

• In humans and other mammals, mutations in genes on the X chromosome result in abnormalities that are manifested differently between the sexes because males are hemizygous for the X.
• Dosage compensation between the mammalian sexes is achieved by inactivating one of the two X chromosomes.
• In males, the sole X remains active in every cell, and each daughter must receive her father's sole X chromosome.
• For X-linked recessive diseases, males manifest the disease, and rarely females, with no father-to-son transmission.
• Carrier females are usually asymptomatic, but a minority of carrier females may present with a mild form of the phenotype due to X inactivation.
• Around 515 X-linked recessive traits are known in humans, with varying frequencies in different ethnic groups.

X Inactivation and Dosage Compensation

• X inactivation is an epigenetic paradigm that normalizes the expression levels of X-linked genes between males and females.
• In abnormal cells with multiple X chromosomes, all but one is inactivated, and this applies to both male and female cells.
• Work by Mary Lyon established that the condensed chromosome observed in 46XX female cells was the inactive one, and that the cells retained a memory of which X was inactivated.
• Females are mosaic for genes on the X, with some cells expressing alleles from the paternally inherited X and others expressing alleles from the maternally inherited X.
• Some genes escape X inactivation, being expressed from both X chromosomes, often having copies on the Y chromosome.

Epigenetic Modifications and Genome Function

• Epigenetic modifications regulate a range of processes in mammalian cells, including chromosome architecture, silencing of repetitive transposable elements, and dynamic and somatically heritable changes in gene expression.
• Epigenetic modifications are chemical marks on the DNA (especially DNA methylation) and post-translational modifications to chromatin-associated histone proteins.
• DNA methylation occurs on CG dinucleotides and is symmetrical on the two DNA strands.
• Histone modifications are established by 'writers', interpreted by 'readers', and can be reversed by 'erasers'.
• Epigenetic modifications contribute to the architecture and function of the genome, and can be over short regulatory elements or over longer regions of DNA.

Learn about the discovery of sex chromosomes, their importance, and sex linkage. Understand the XY and ZW sex determining systems and their evolution.