Testis-enriched heat shock protein A2 (HSPA2): Adaptive advantages of the birds with internal testes over the mammals with testicular descent

Abstract

The molecular chaperone heat shock protein A2 (HSPA2), a member of the 70 kDa heat shock protein (HSP70) family, plays an important role in spermatogenesis and male fertility. Although HSPA2 is evolutionarily highly conserved across the metazoan lineages, the observation of striking differences in temperature-sensitive expressions, testicular physiology, spermatogenesis, as well as its role in male fertility indicates that avian and mammalian HSPA2 may exhibit distinct evolutionary trajectory. The present study reports that while mammalian HSPA2 is constrained by intense purifying selection, avian HSPA2 has been subjected to positive selection. The majority of the positively selected amino acid residues fall on the α-helix and β-sheets of the peptide-binding domain located at the carboxyl-terminal region of the avian HSPA2. The detection of positively selected sites at the helix and β-sheets, which are less tolerant to molecular adaptation, indicates an important functional consequence and contribution to the structural and functional diversification of the avian HSPA2. Collectively, avian HSPA2 may have an adaptive advantage over the mammals in response to heat stress, and therefore, mammals with testicular descent may be at a greater risk in the event of scrotal temperature rise.

Integrative functional genomic analysis of intron retention in human and mouse brain with Alzheimer's disease

“…PRPF40B is a splicing factor involved in pre‐mRNA splicing. HSPA2 is a heat shock protein that mediates folding of proteins, is associated with assembly of spliceosomes, and is involved in cellular stress response 68 . Notably, the PathCards database shows that HSPA2 has only low‐ranking evidence for being involved in the general splicing pathway, but it appears to be a major player in IR based on our network.…”

“…HSPA2 is a heat shock protein that mediates folding of proteins, is associated with assembly of spliceosomes, and is involved in cellular stress response. 68 Notably, the PathCards database shows that HSPA2 has only low-ranking evidence for being involved in the general splicing pathway, but it appears to be a major player in IR based on our network. Some of the major splicing factors such as SNRNP70, PRPF40B, SRRM1, and ACIN1 appear in both the AD-and controlspecific SPIRONs, suggesting the conservation of major splicing factors in different conditions.…”

Spermatogenesis-associated proteins at different developmental stages of buffalo testicular seminiferous tubules identified by comparative proteomic analysis

“…It has been shown recently that the molecular chaperone HSPA2 plays a pivotal role in mediating sperm–oocyte binding and facilitates the formation of multimeric zona pellucid‐receptor complexes on the surface of mammalian spermatozoa during capacitation . Thus, HSPA2 is increasingly being recognized as an important regulator of fertility, and its expression is responsive to heat stress . These findings have significant implications for the role of HSPA2 in buffalo bull fertility, as well as among breeds of buffalo differentially adapted to various climates.…”

Study of evolution and architecture of minimal introns

“…The HSPA2 in mammals, however, is unlikely to function efficiently during prolonged exposure to high temperature. 162 These observations corroborate our hypothesis of disruption in the mRNA processing of low GC% minimal intron-containing genes during the elevated temperature of spermatogenesis. As a result, more defected proteins may be produced that leads to ubiquitination or even to the chaperone pathway due to misfolding.…”