Progressive inactivation of the haploid expressed gene for the sperm-specific endozepine-like peptide (ELP) through primate evolution

The endozepine-like peptide (ELP) is a novel intracellular molecule which i s expressed in high amounts at both mRNA and protein levels very specifical ly in late haploid male germ cells. It is closely related to the ubiquitous acyl-CoA binding protein, is highly conserved, shares a similar ability to bind mid-long chain acyl-CoA, and is thus likely to be involved in mature sperm metabolism While it has been characterized from diverse mammals, it h as so far not been possible to identify an equivalent molecule in the prima te testis. Using a PCR approach, combined with cDNA cloning and Northern hy bridization, testicular transcripts and/or genomic DNA were analysed for di fferent primate species, including human. In the marmoset and cynomolgus ma caque normally structured transcripts appear to be expressed, though at a l ow level. In the human testis, two ran transcripts were characterized, hELP 1 and hELP2, the products of independent duplicated genes. Both transcripts were longer than in nonmammalian species, included frame-shift mutations a nd substantial sequence insertions, preventing the translation of a sensibl e protein. Genomic PCR analysis of three anthropoid species, chimpanzee, go rilla and orangutan, showed the presence of a similarly mutated hELP1 gene. Only in the gorilla was a hELP2 gene identified, apparently lacking the Fr ame-shift mutation, and thus potentially able to give rise to a functional ELF protein. Taken together, these results show that during primate evoluti on there has been a progressive inactivation of the ELF gene, initially wit h a down-regulation in lower primates, and subsequently with inactivating m utations in the open reading frame. At some time during simian evolution pr ior to these mutations there has been a gene duplication, though this secon d gene has also become inactivated in humans. In its pattern of evolution t he ELF gene shows similarities with the MDC/fertilin family, whose members are also considered essential components of haploid sperm in non-primates, but which are progressively inactivated in anthropoids and humans. We shoul d like to speculate that the established subfertility of the human male may not be a recent event, but the consequence of a longer evolutionary proces s whereby primates have traded off absolute fertility against social or sex ual advantages. (C) 2000 Elsevier Science B.V. All rights reserved.