Differential divergence of three human pseudoautosomal genes and their mouse homologs: Implications for sex chromosome evolution

Autor: Antonino Forabosco, Nicoletta Archidiacono, Fernando Gianfrancesco, Gudrun A. Rappold, Sergio Tempesta, Ercole Rao, Teresa Esposito, Remo Sanges, Jennifer A. Marshall Graves, Michele D'Urso
Jazyk: angličtina
Rok vydání: 2001
Předmět:
Zdroj: Genome research 11 (2001): 2095–2100. doi:10.1101/gr.197001
info:cnr-pdr/source/autori:Gianfrancesco F, Sanges R, Esposito T, Tempesta S, Rao E, Rappold G, Archidiacono N, Graves JA, Forabosco A, D'Urso M./titolo:Differential divergence of three human pseudoautosomal genes and their mouse homologs: implications for sex chromosome evolution./doi:10.1101%2Fgr.197001/rivista:Genome research/anno:2001/pagina_da:2095/pagina_a:2100/intervallo_pagine:2095–2100/volume:11
DOI: 10.1101/gr.197001
Popis: The human sex chromosomes, heteromorphic in both size and gene content, are fossils of an ancestral, homologous chromosome pair (Ohno 1967). Over the 200 million years of mammalian evolution, the X and Y chromosomes lost homology as the Y chromosome was progressively degraded as the result of drift in nonrecombining regions and/or selection at linked loci on the Y (Charlesworth 1990). However, pseudoautosomal regions 1 and 2 (PAR1 and PAR2) at the termini of the short and long arms of X and Y chromosomes still recombine during male meiosis, ensuring X-Y nucleotide sequence identity that is necessary for normal male meiosis (Rappold 1993). In this paper, we will consider only the short-arm PAR1. Between-species comparisons of the PAR and neighboring X-specific regions have aided our understanding of the genesis of this region, but also have presented mysteries. Cloning and mapping the marsupial homologs of genes within and near the human PAR1 revealed that this region was added to the X and Y since the divergence of marsupials and eutherian mammals 130 million years ago (Toder and Graves 1998). Comparisons with carnivores and artiodactyls showed that the human PAR1 has been recently reduced from a larger homologous region that included the steroid sulfatase (STS) gene, which lies just outside the PAR on the human X chromosome, and detects an inactive copy on the long arm of the human Y (Toder et al. 1997). Comparison with mouse genes is harder to interpret. Human and mouse pseudoautosomal regions appear to have distinct evolutionary origin, as there are no genes that are pseudoautosomal in both species. Of the 10 cloned genes assigned to the human PAR1, eight appear to have no mouse homologs. The two that do recognize mouse homologs, Csfgmra (the homolog of CSF2RA) and Il3ra (the homolog of IL3RA), both have diverged considerably from their human homologs (Hara and Miyajima 1992; Park et al. 1992) and both have been assigned to mouse autosomes (chromosomes 19 and 14, respectively) (Disteche et al. 1992; Ellison et al. 1996). The only gene assigned to the PAR of the mouse is steroid sulfatase (Sts), which is pseudoautosomal in other eutherians, but not human. Mouse Sts is very divergent from human STS (63% identity at nucleotide and 59% at amino-acid levels [Salido et al. 1996]). Spanning the boundary of the mouse PAR is the gene Fxy, which codes for a RING finger protein. The human homolog FXY is located on Xp22.3, near but not within PAR1 (Perry et al. 1998). The 5′ region of the mouse gene (exons 1–3, including a significant portion of the coding region) has no Y homolog, while the 3′ region (exons 4–10) lies within PAR1 and therefore is present both on the X and Y chromosomes. Human FXY and mouse Fxy shows a very high sequence similarity at the DNA and protein levels, but the X-Y shared 3′ region is much less conserved (estimated at 170-fold higher for synonymous sites) than the 5′ portion (Perry and Ashworth 1999). It is hard to explain why genes in the pseudoautosomal region should diverge more rapidly than genes in the differentiated region of the X chromosome or the autosomes. It is not clear, from the few human genes with mouse homologs, how general this observation is. It would be a great advantage to analyze other human PAR1 genes with mouse homologs. To further explore the relationship between human and mouse PARs, we have isolated a novel pseudoautosomal human gene called DHRSXY and undertaken comparative studies of this and two other genes that we have recently isolated: PGPL and TRAMP. We found a highly conserved mouse ortholog of PGPL and a less conserved mouse ortholog of DHRSXY, both of which are autosomal. There appears to be no mouse TRAMP ortholog. We discuss the implications of this finding in understanding the evolution of the pseudoautosomal region.
Databáze: OpenAIRE
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