The human RPS4 paralogue on Yq11.223 encodes a structurally conserved ribosomal protein and is preferentially expressed during spermatogenesis.
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.
Lopes
Alexandra M
AM
Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Portugal. alopes@ipatimup.pt
Miguel
Ricardo N
RN
Sargent
Carole A
CA
Ellis
Peter J
PJ
Amorim
António
A
Affara
Nabeel A
NA
D001483:Base Sequence; D041322:Chromosomes, Human, Y; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013091:Spermatogenesis / Q000502:physiology*
D020033:Protein Isoforms; C551796:RPS4Y2 protein, human; D012269:Ribosomal Proteins; C031798:ribosomal protein S4
Nat Genet. 1993 Jul;4(3):268-71
8358435
Annu Rev Biochem. 1985;54:507-30
3927820
J Med Genet. 2000 Oct;37(10):752-8
11015452
Front Biosci. 2006 Sep 01;11:3049-61
16720375
Recent Prog Horm Res. 2002;57:103-28
12017539
J Med Genet. 2007 Aug;44(8):498-508
17496197
Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9538-41
8415737
Structure. 2009 Dec 9;17(12):1591-1604
20004163
Cancer Cell. 2003 Jun;3(6):577-87
12842086
Science. 2000 Aug 11;289(5481):905-20
10937989
Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):13-20
8552589
Nature. 2005 Sep 1;437(7055):100-3
16136134
Science. 1991 Mar 1;251(4997):1030-3
1998119
J Mol Biol. 1971 Feb 14;55(3):379-400
5551392
BMC Evol Biol. 2008 May 13;8:142
18477388
Nature. 1996 May 23;381(6580):272
8692262
Bioinformatics. 1998;14(7):617-23
9730927
Mol Biol Evol. 2007 Mar;24(3):853-9
17218643
EMBO J. 1982;1(3):357-62
6201358
Nat Genet. 2001 Nov;29(3):279-86
11687796
Science. 2006 Sep 29;313(5795):1935-42
16959973
Nature. 2000 Sep 21;407(6802):327-39
11014182
Bioinformatics. 2001 Aug;17(8):748-9
11524380
J Mol Biol. 1993 Dec 5;234(3):779-815
8254673
Development. 2000 Jan;127(1):143-53
10654608
J Mol Biol. 2001 Jun 29;310(1):243-57
11419950
Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):13953-8
18768810
Blood. 2006 Jun 15;107(12):4583-8
16507776
Mol Cell Biol. 1994 Apr;14(4):2485-92
8139551
Nature. 2003 Jun 19;423(6942):825-37
12815422
Mol Hum Reprod. 2004 Oct;10(10):743-53
15299089
Genome Res. 2002 Mar;12(3):379-90
11875025
J Mol Biol. 1984 Sep 5;178(1):63-89
6548264
J Mol Biol. 1994 May 20;238(5):777-93
8182748
Nature. 1992 Mar 5;356(6364):83-5
1538787
Hum Genet. 1976 Oct 28;34(2):119-24
1002136
Nat Genet. 2001 Sep;29(1):49-53
11528390
Cell. 1990 Dec 21;63(6):1205-18
2124517
Mol Cell Biol. 2004 Sep;24(17):7654-68
15314173
J Mol Biol. 1993 Jun 20;231(4):1049-67
8515464
J Exp Zool. 1998 Aug 1;281(5):472-81
9662834
Genomics. 1996 Jan 1;31(1):44-50
8808278
Nature. 2000 Sep 21;407(6802):340-8
11014183
Mol Biol Evol. 1998 Nov;15(11):1412-9
12572605
Nat Rev Genet. 2001 Mar;2(3):207-16
11256072
Nat Genet. 2006 Feb;38(2):158-67
16388311