Transcripts encoding the sperm surface protein tMDC II are non-functional in the human

Abstract

Five members of the MDC (metalloproteinase-like,disintegrin-like cysteine-rich domain) family of proteins (fertilin α, fertilin β, tMDC I, tMDC II and tMDC III) are expressed on the surface of macaque (Macaca fascicularis) sperm, where they have been proposed to play a role in sperm-egg binding via an interaction between their disintegrin-like domain and one or more integrins on the egg plasma membrane. Of these, two (fertilin α and tMDC I) have recently been shown to be non-functional in the human. Here we report the existence of multiple isoforms of human tMDC II transcripts in the human, all of which are also non-functional owing to the presence of deletions and in-frame termination codons, when compared with the macaque orthologue, a finding which is further supported by the lack of immunoreactivity on Western blots of human testis and sperm extracts probed with a macaque anti-tMDC II polyclonal antiserum. These results are discussed in the context of our proposed model for multiple proteins implicated in sperm-egg interactions.

Evolution of the Hominoid Semenogelin Genes, the Major Proteins of Ejaculated Semen

“…In addition to the independent acquisition of multiple premature stop codons in several hominoid lineages at both the SEMG1 and the SEMG2 genes described herein, several other male reproductive genes have lost their function recently in hominoid evolution including the fertilin-a (a.k.a. ADAM1) genes in human (Jury et al 1997) and independently in gorilla (Jury et al 1998), the spermegg binding proteins tMDCI and tMDCII genes in A T T + G T C G G 12 Hap2 G A A + T T T T G 1 Hap3 A A T + G T C T G 1 Hap4 A humans (Frayne et al 1998(Frayne et al , 1999, the sperm-specific ELP1 gene in the great apes (Ivell et al 2000), and ELP2 gene in humans (Ivell et al 2000). Whether or not there is a relationship between the tendency for male reproductive genes to evolve rapidly and the tendency for them to become pseudogenes is unknown, but it is conceivable that rapid Darwinian evolution (high K a /K s ) can result in a protein that is too specialized to perform its original function if the specific selective pressures driving its evolution are to change, rendering the gene useless.…”

The evolution of the vertebrate metzincins; insights from Ciona intestinalis and Danio rerio

“…The highly specific function of these genes in relation to mammalian biology infers that they evolved more recently during tetrapod evolution. Indeed all of these genes (including the human ADAM3 and ADAM5 pseudogenes) are located at chromosome 8p11.22-23, inferring that this group evolved by tandem duplication and that the pseudogenization of human ADAM3 and ADAM5 [48,49] occurred after the divergence of the rodent and primate lineages.…”

Mechanisms of sperm-egg interactions emerging from gene-manipulated animals

“…However, multiple isoforms of Adam3 transcripts observed in the human were non-functional owing to the presence of deletions and in-frame termination codons (Frayne et al, 1999). Therefore, ADAM3 cannot be an ultimate universal zona-binding factor among mammals.…”

“…In the sperm-zona binding event, ADAM3 holds the central position in the mouse, but the equivalent gene in human seems to be not producing functional protein (Frayne et al, 1999). We were curious to see if Izumo is species-specific.…”