Research Area

• Mammalian X-Chromosome Inactivation
• Dosage Compensation
• Sex Determination
• X-Chromosome Organization

Research

Mammalian X-chromosome inactivation has traditionally been viewed as a mechanism of dosage compensation, balancing the activity of X-linked genes between males and females.

The evolutionary explanation for dosage compensation was developed through the work of Lyon and Ohno. Ohno proposed a two-step evolutionary process in which the activity of the single X chromosome in males was enhanced, followed by X-chromosome inactivation in females to bring X-linked gene activity back to disomic levels.

For over four decades, Ohno's hypothesis has provided an important framework for understanding the evolution of heteromorphic sex chromosomes, X-chromosome inactivation and dosage compensation in mammals.

X-Chromosome & Sex Determination

In 1985, based on the observation that certain segments of the X and Y chromosomes are homologous, Prof. Chandra proposed that X-chromosome inactivation could have a role in sex determination.

Although the subsequent discovery of SRY made this hypothesis less likely, work on the human X chromosome has shown that it is rich in genes associated with maleness.

From published literature, eight genes for maleness on the human X chromosome have been identified as dosage-sensitive and are known to cause sex reversal when their dosage is abnormal.

Based on these observations, Prof. Chandra has proposed that in humans and other eutherian mammals, a function of X-chromosome inactivation may be the suppression of maleness in genetic females.

Current Research

Current work is examining X-chromosome gene content and the differences in the location of sex-reversal genes compared with autosomal genes with similar functions, with the aim of identifying useful clues from the organization of the X chromosome.

Selected Publications

1. Dosage compensation from the viewpoint of natural selection. Chandra, H. S. and Nanjundiah, V.
   In: Sex Chromosomes and Sex-determining Genes, Eds. K. C. Reed and J. A. Marshall Graves.
   Harwood Academic, Switzerland, 1993.
2. X chromosomes and dosage compensation. Chandra, H. S.
   Nature, 319: 18, 1986.
3. Is human X-chromosome inactivation a sex-determining device? Chandra, H. S.
   Proceedings of the National Academy of Sciences, USA, 82: 6947–6949, 1985.
4. Mammalian X-chromosome inactivation: proposed role in suppression of the male programme in genetic females. Chandra, H. S.
   Journal of Genetics, 101, 23, 2022.
   DOI: 10.1007/s12041-022-01363-0 ↗