Abstract
BackgroundRodent and primate pregnancy-specific glycoprotein (PSG) gene families have expanded independently from a common ancestor and are expressed virtually exclusively in placental trophoblasts. However, within each species, it is unknown whether multiple paralogs have been selected for diversification of function, or for increased dosage of monofunctional PSG. We analysed the evolution of the mouse PSG sequences, and compared them to rat, human and baboon PSGs to attempt to understand the evolution of this complex gene family.ResultsPhylogenetic tree analyses indicate that the primate N domains and the rodent N1 domains exhibit a higher degree of conservation than that observed in a comparison of the mouse N1 and N2 domains, or mouse N1 and N3 domains. Compared to human and baboon PSG N domain exons, mouse and rat PSG N domain exons have undergone less sequence homogenisation. The high non-synonymous substitution rates observed in the CFG face of the mouse N1 domain, within a context of overall conservation, suggests divergence of function of mouse PSGs. The rat PSG family appears to have undergone less expansion than the mouse, exhibits lower divergence rates and increased sequence homogenisation in the CFG face of the N1 domain. In contrast to most primate PSG N domains, rodent PSG N1 domains do not contain an RGD tri-peptide motif, but do contain RGD-like sequences, which are not conserved in rodent N2 and N3 domains.ConclusionRelative conservation of primate N domains and rodent N1 domains suggests that, despite independent gene family expansions and structural diversification, mouse and human PSGs retain conserved functions. Human PSG gene family expansion and homogenisation suggests that evolution occurred in a concerted manner that maintains similar functions of PSGs, whilst increasing gene dosage of the family as a whole. In the mouse, gene family expansion, coupled with local diversification of the CFG face, suggests selection both for increased gene dosage and diversification of function. Partial conservation of RGD and RGD-like tri-peptides in primate and rodent N and N1 domains, respectively, supports a role for these motifs in PSG function.
Highlights
Rodent and primate pregnancy-specific glycoprotein (PSG) gene families have expanded independently from a common ancestor and are expressed virtually exclusively in placental trophoblasts
Pairwise comparisons of all 4-domain mouse PSG with all 4-domain human PSG full-length amino acid sequences indicates conservation of the amino-terminal N domain With the exception of mouse PSG24, PSG30 and PSG31 and human PSG2 and PSG5, all PSGs for which full length sequences are available have a structure based on four Ig-like domains and a leader sequence that is cleaved during post-translational processing
Evidence of conservation of RGD-like motifs in mouse N1 domains Within Box 3 of the CFG face (Fig. 7A) there is evidence of conservation of putative integrin-interacting RGD-like motifs in the mouse N1 domain, which may have functional significance
Summary
Rodent and primate pregnancy-specific glycoprotein (PSG) gene families have expanded independently from a common ancestor and are expressed virtually exclusively in placental trophoblasts. There are multigene families whose members encode diverse functions e.g. genes encoding immunoglobulin (Ig), T cell receptor (TCR) and major histocompatibility complex (MHC) proteins [1] Such diversity occurs when there is less homogenisation than mutation, due to the evolution of specific programmed mutational mechanisms [3]. More complex modes exist; for example, the immunoglobulin heavy-chain variableregion (VH) genes encode proteins with identical functions, but exhibit little concerted evolution [4]. Instead, their evolution is governed by divergence and a birth-anddeath process of gene duplication and dysfunctioning mutations [2]
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