The Xist RNA Gene Evolved in Eutherians by Pseudogenization of a Protein-Coding Gene

The Xist RNA Gene Evolved in Eutherians by Pseudogenization of a Protein-Coding Gene Duret et al. (2006)

Background • Gene dosage is compensated by X-chromosome inactivation (XCI) • In eutherians, XCI involves the Xist gene and the X inactivation center (Xic) • Hypothesize that XCI emerged early in mammalian evolution with sex determination

Overview • Objective: To understand the evolution of X inactivation in placental mammals • Method: - Search for homologous genes - Perform genomic alignments

Fig. 1 - Xist homologs eutherians

Fig. 2A - Xic vs. XicHR • All vertebrate classes: Cdx4, Chic1, Xpct • Eutherians: Jpx, Ftx, Tsx, Cnbp2 • Non-eutherian: Fip1l2, Lnx3, Rasl11c, UspL, Wave4

Fig. 2B - Tsx • Tsx shows homology with three exons of Fip1l2 • Mouse Tsx: functional truncated gene • Human Tsx: pseudogene

Fig. 2C - Xist • Xist is homologous to two exons of Lnx3

Fig. 3A - Lnx3 and Xist • Two exons of Xist are derived from Lnx3.

Fig. 3B - Lnx3 and Xist

Summary • Xist partially evolved from a protein-coding gene • Loss of protein coding function for proto-Xist coincides with four flanking protein genes also becoming pseudogenes • Loss of function occurred after divergence between eutherians and marsupials • Mechanisms of dosage compensation have evolved independently in eutherians and marsupials

The Xist RNA Gene Evolved in Eutherians by Pseudogenization of a Protein-Coding Gene