Hominoid-specific SPANXA/D genes demonstrate differential expression in individuals and protein localization to a distinct nuclear envelope domain during spermatid morphogenesis

Abstract

Human sperm protein associated with the nucleus on the X chromosome consists of a five-member gene family (SPANXA1, SPANXA2, SPANXB, SPANXC and SPANXD) clustered at Xq27.1. Evolved from an ancestral SPANX-N gene family (at Xq27 and Xp11) present in all primates as well as in rats and mice, the SPANXA/D family is present only in humans, bonobos, chimpanzees and gorillas. Among hominoid-specific genes, the SPANXA/D gene family is considered to be undergoing rapid positive selection in its coding region. In this study, RT-PCR of human testis mRNA from individuals showed that, although all SPANXA/D genes are expressed in humans, differences are evident. In particular, SPANXC is expressed only in a subset of men. The SPANXa/d protein localized to the nuclear envelope of round, condensing and elongating spermatids, specifically to regions that do not underlie the developing acrosome. During spermiogenesis, the SPANXa/d-positive domain migrated into the base of the head as the redundant nuclear envelope that protrudes into the residual cytoplasm. Post-testicular modification of the SPANXa/d proteins was noted, as were PEST (proline, glutamic acid, serine, and threonine rich regions) domains. It is concluded that the duplication of the SPANX-N gene family that occurred 6-11 MYA resulted in a new gene family, SPANXA/D, that plays a role during spermiogenesis. The SPANXa/d gene products are among the few examples of X-linked nuclear proteins expressed following meiosis. Their localization to non-acrosomal domains of the nuclear envelope adjacent to regions of euchromatin and their redistribution to the redundant nuclear envelope during spermiogenesis provide a biomarker for the redundant nuclear envelope of spermatids and spermatozoa.

SPANXA suppresses EMT by inhibiting c-JUN/SNAI2 signaling in lung adenocarcinoma

“…SPANXA is an acidic protein and associates with other nuclear envelope proteins, but shows no significant similarity with known nuclear proteins or nucleic acid-binding proteins in the spermatid [16, 19]. These studies implied that SPANXA may interact with nucleic acids or other proteins in performing its functions.…”

“…The SPANX (Sperm Protein Associated with the Nucleus on the X-chromosome) family encodes highly similar proteins that are exclusively expressed in normal testes as well as in certain tumors [14–17]. In adult human testes, SPANXA/D (A1, A2, B, C, and D) proteins are localized on the nuclear envelope of condensing non-acrosomal regions during spermiogenesis, and expressed in late spermatids and spermatozoa [18, 19]. SPANXA/D proteins have also been found in various tumors, such as melanoma, bladder carcinomas, myeloma, head and neck squamous cell carcinoma (HNSCC), as well as colorectal and prostate cancers [14, 20–23].…”

New genes contribute to genetic and phenotypic novelties in human evolution

“…A recent case study provided the valuable insight into the biological role of testis-biased expressed new genes. A better-characterized case is SPANXA/D family, which consists of three X-linked sperm proteins associated with nucleus, SPANXA1, SPANXA2 and SPANXD present only in human and great ape [24]. It was found that during spermatid morphogenesis, the SPANXA/D protein migrated into the base of the sperm head [24].…”

Evolutionary Diversification of SPANX-N Sperm Protein Gene Structure and Expression

“…The genes expressed during spermatogenesis comprise diploid and haploid expressed groups [1]. Many of the haploid, post-meiotically expressed genes have been mapped to autosomal chromosomes, but the s perm p rotein a ssociated with n ucleus in the X chromosome ( SPANX ) gene family is one of the few mapped to the X chromosome [2]–[4].…”