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, Wa

ve4

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 coi

ncides 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