The Xist RNA Gene Evolved in Eutherians by Pseudogenization of a Protein-Coding Gene
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The Xist RNA Gene Evolved in Eutherians by Pseudogenization of a
Protein-Coding Gene
Duret et al. (2006)
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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
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Overview
• Objective:
To understand the evolution of X inactivation in placental mammals
• Method:
- Search for homologous genes
- Perform genomic alignments
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Fig. 1 - Xist homologs
eutherians
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Fig. 2A - Xic vs. XicHR
• All vertebrate classes: Cdx4, Chic1, Xpct• Eutherians: Jpx, Ftx, Tsx, Cnbp2• Non-eutherian: Fip1l2, Lnx3, Rasl11c, UspL, Wa
ve4
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Fig. 2B - Tsx
• Tsx shows homology with three exons of Fip1l2• Mouse Tsx: functional truncated gene• Human Tsx: pseudogene
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Fig. 2C - Xist
• Xist is homologous to two exons of Lnx3
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Fig. 3A - Lnx3 and Xist
• Two exons of Xist are derived from Lnx3.
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Fig. 3B - Lnx3 and Xist
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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
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