Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 May 7:11:33.
doi: 10.1186/1471-2199-11-33.

The human RPS4 paralogue on Yq11.223 encodes a structurally conserved ribosomal protein and is preferentially expressed during spermatogenesis

Alexandra M Lopes  1 , Ricardo N Miguel, Carole A Sargent, Peter J Ellis, António Amorim, Nabeel A Affara
Affiliations

The human RPS4 paralogue on Yq11.223 encodes a structurally conserved ribosomal protein and is preferentially expressed during spermatogenesis

Alexandra M Lopes et al. BMC Mol Biol. .

Abstract

Background: The Y chromosome of mammals is particularly prone to accumulate genes related to male fertility. However, the high rate of molecular evolution on this chromosome predicts reduced power to the across-species comparative approach in identifying male-specific genes that are essential for sperm production in humans. We performed a comprehensive analysis of expression of Y-linked transcripts and their X homologues in several human tissues, and in biopsies of infertile patients, in an attempt to identify new testis-specific genes involved in human spermatogenesis.

Results: We present evidence that one of the primate-specific Y-linked ribosomal protein genes, RPS4Y2, has restricted expression in testis and prostate, in contrast with its X-linked homologue, which is ubiquitously expressed. Moreover, we have determined by highly specific quantitative real time PCR that RPS4Y2 is more highly expressed in testis biopsies containing germ cells. The in silico analysis of the promoter region of RPS4Y2 revealed several differences relative to RPS4Y1, the more widely expressed paralogue from which Y2 has originated through duplication. Finally, through comparative modelling we obtained the three dimensional models of the human S4 proteins, revealing a conserved structure. Interestingly, RPS4Y2 shows different inter-domain contacts and the potential to establish specific interactions.

Conclusions: These results suggest that one of the Y-linked copies of the ribosomal protein S4 is preferentially expressed during spermatogenesis and might be important for germ cell development. Even though RPS4Y2 has accumulated several amino acid changes following its duplication from RPS4Y1, approximately 35 million years ago, the evolution of the Y-encoded RPS4 proteins is structurally constrained. However, the exclusive expression pattern of RPS4Y2 and the novelties acquired at the C-terminus of the protein may indicate some degree of functional specialisation of this protein in spermatogenesis.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Analysis of expression of RPS4 transcripts. (A) Structure of the transcripts analysed; the arrows represent the direction of transcription (forward or reverse strand). (B) Expression patterns of the RPS4X, RPS4Y1 and RPS4Y2 transcripts in a panel of 17 human tissues (Ambion First Choice RNA Panel). Each tissue sample is derived from a pool of individuals (males and/or females). Last lane is the no template control.
Figure 2
Figure 2
Expression of RPS4 genes in testis biopsies of five infertile individuals. All samples had been previously characterized by histology and global expression profiling [17] (3 subjected to vasectomy - VAS1, VAS3, VAS5; 2 azoospermic patients - AZ7, AZ9). (A) End-point detection of RT-PCR products of RPS4XY isoforms by electrophoresis. Last lane is the no template control. (B) Quantitative real time PCR using an RPS4Y2 TaqMan probe. The values correspond to the mean of two independent measurements of relative expression using GAPDH as an endogenous control for normalization. The error bars refer to one standard deviation to the mean of the two experimental replicates.
Figure 3
Figure 3
Sequence motifs found within the promoter regions of RPS4Y1 and RPS4Y2. The numbers indicate nucleotide positions relative to the TSS, according to [18]. For RPS4Y2, we considered that the TSS overlaps the ATG. Hyphens represent inserted/deleted nucleotides. The olygopyrimidine tract overlapping the RPS4Y1 transcription start site is underlined. Arrows indicate the orientation of the predicted transcription factor binding sites (forward or reverse strand). The positions within the sequence motifs that differ between the two genes are in italic.
Figure 4
Figure 4
Three dimensional models of isolated RPS4 proteins. The N and C termini are marked. (A) Structure of each RPS4 protein. β strands are in yellow, α helices in red and loops in green. (B) RPS4X showing the one residue that is different in the three RPS4 proteins (carbon atoms in cyan, oxygen atoms in red and nitrogen atoms in blue) and the residues that are different, with non-conservative substitutions, in one or both of the RPS4Y proteins (carbon atoms in grey, oxygen atoms in red and nitrogen atoms in blue). N-terminal domain is in green, central domain in yellow and C-terminal domain in cyan.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Tiepolo L, Zuffardi O. Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm. Hum Genet. 1976;34(2):119–124. doi: 10.1007/BF00278879. - DOI - PubMed
    1. Kuroda-Kawaguchi T, Skaletsky H, Brown L, Minx P, Cordum H, Waterston R, Wilson R, Silber S, Oates R, Rozen S. The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men. Nat Genet. 2001;29(3):279–286. doi: 10.1038/ng757. - DOI - PubMed
    1. Skaletsky H, Kuroda-Kawaguchi T, Minx P, Cordum H, Hillier L, Brown L, Repping S, Pyntikova T, Ali J, Bieri T. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature. 2003;423(6942):825–837. doi: 10.1038/nature01722. - DOI - PubMed
    1. Blanco P, Shlumukova M, Sargent C, Jobling M, Affara N, Hurles M. Divergent outcomes of intrachromosomal recombination on the human Y chromosome: male infertility and recurrent polymorphism. J Med Genet. 2000;37(10):752–758. doi: 10.1136/jmg.37.10.752. - DOI - PMC - PubMed
    1. Krausz C, Degl'Innocenti S. Y chromosome and male infertility: update, 2006. Front Biosci. 2006;11:3049–3061. doi: 10.2741/2032. - DOI - PubMed

Publication types

LinkOut - more resources