Is human X chromosome inactivation a sex-determining device?

Area of Science:

• Genetics
• Evolutionary Biology
• Developmental Biology

Background:

• X chromosome inactivation is traditionally viewed as a mechanism for gene dosage compensation.
• Evidence for the necessity of dosage compensation for most X-linked genes is limited.
• An alternative hypothesis suggests a role for X chromosome inactivation in sex determination.

Purpose of the Study:

• To examine the hypothesis that X chromosome inactivation is primarily involved in sex determination.
• To explore how differential gene copy number and inactivation could lead to distinct sexes.

Main Methods:

• Theoretical examination of gene regulation and copy number in sex determination.
• Analysis of DNA sequences, such as the human banded krait minor satellite, in relation to sex chromosomes.
• Comparison with similar phenomena in insect species.

Main Results:

• A model is proposed where differential copy number of key regulatory sequences on X and Y chromosomes, combined with X inactivation, establishes sex.
• Human sex determination may involve X inactivation reducing the effective copy number of X-linked sex-determining sequences.
• Analogous chromosome inactivation in insects is associated with maleness, supporting the proposed mechanism.

Conclusions:

• X chromosome inactivation may serve as the primary mechanism for establishing sexual dimorphism.
• This process creates a critical genetic inequality between male and female embryos.
• The findings suggest a re-evaluation of the primary evolutionary function of X chromosome inactivation.