Evolutionary diversification of SPANX-N sperm protein gene structure and expression.
The sperm protein associated with nucleus in the X chromosome (SPANX) genes cluster at Xq27 in two subfamilies, SPANX-A/D and SPANX-N. SPANX-A/D is specific for hominoids and is fairly well characterized. The SPANX-N gave rise to SPANX-A/D in the hominoid lineage approximately 7 MYA. Given the proposed role of SPANX genes in spermatogenesis, we have extended studies to SPANX-N gene evolution, variation, regulation of expression, and intra-sperm localization. By immunofluorescence analysis, SPANX-N proteins are localized in post-meiotic spermatids exclusively, like SPANX-A/D. But in contrast to SPANX-A/D, SPANX-N are found in all ejaculated spermatozoa rather than only in a subpopulation, are localized in the acrosome rather than in the nuclear envelope, and are expressed at a low level in several nongametogenic adult tissues as well as many cancers. Presence of a binding site for CTCF and its testis-specific paralogue BORIS in the SPANX promoters suggests, by analogy to MAGE-A1 and NY-ESO-1, that their activation in spermatogenesis is mediated by the programmed replacement of CTCF by BORIS. Based on the relative density of CpG, the more extended expression of SPANX-N compared to SPANX-A/D in nongametogenic tissues is likely attributed to differences in promoter methylation. Our findings suggest that the recent duplication of SPANX genes in hominoids was accompanied by different localization of SPANX-N proteins in post-meiotic sperm and additional expression in several nongonadal tissues. This suggests a corresponding functional diversification of SPANX gene families in hominoids. SPANX proteins thus provide unique targets to investigate their roles in the function of spermatozoa, selected malignancies, and for SPANX-N, in other tissues as well.
Kouprina
Natalay
N
Laboratory of Molecular Pharmacology, National Cancer Institute (NCI), National Institutes of Health, Bethesda, Maryland, United States of America. kouprinn@mail.nih.gov
Noskov
Vladimir N
VN
Pavlicek
Adam
A
Collins
N Keith
NK
Schoppee Bortz
Pamela D
PD
Ottolenghi
Chris
C
Loukinov
Dmitri
D
Goldsmith
Paul
P
Risinger
John I
JI
Kim
Jung-Hyun
JH
Westbrook
V Anne
VA
Solomon
Gregory
G
Sounders
Hanna
H
Herr
John C
JC
Jurka
Jerzy
J
Lobanenkov
Victor
V
Schlessinger
David
D
Larionov
Vladimir
V
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D045744:Cell Line, Tumor; D041321:Chromosomes, Human, X; D024202:Electrophoretic Mobility Shift Assay; D019143:Evolution, Molecular; D005455:Fluorescent Antibody Technique; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
D009687:Nuclear Proteins; D011994:Recombinant Proteins; C414403:SPANXA1 protein, human