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