Coevolution of Positively Selected IZUMO1 and CD9 in Rodents: Evidence of Interaction Between Gamete Fusion Proteins?1

Abstract

Proteins involved in sexual reproduction are known to evolve rapidly, often as the result of positive Darwinian selection, although the selective forces driving such adaptive changes are poorly understood. A process of coevolution between proteins in male and female gametes may promote rapid divergence of fertilization proteins. In the mouse, only two proteins have been shown so far to be essential for sperm-egg fusion, IZUMO1 in the sperm cell and CD9 in the egg. The role of these proteins has not been fully elucidated, and it has been suggested that they may act as fusogens, interacting in trans with proteins on the other cell, or regulators of fusogens through cis interactions. Here we analyze the evolution of IZUMO1 and CD9 in a group of rodent species. To assess possible protein interactions between IZUMO1 and CD9, we examined potential coevolution based on analyses of correlated evolutionary rates. We found evidence that both proteins evolve adaptively, with a more intense signal of positive selection in IZUMO1. In addition, our findings suggest that these proteins may have some form of interaction, although they have not been regarded as fusogens interacting directly with each other. The adaptive divergence of IZUMO1 and CD9 could influence reproductive compatibility, and, thus, these proteins may participate in the establishment of specific sperm-egg recognition systems. Further studies are required to uncover the role of IZUMO1 and CD9 during gamete fusion in order to understand the molecular basis of their coevolution, as other selective forces could also lead to general signatures of coevolution.

Izumo1 and Juno: the evolutionary origins and coevolution of essential sperm–egg binding partners

“…The possibility that Izumo1 and Juno are coevolving under the pressures of sexual conflict is also an interesting one, which would probably be best studied in a small clade of species with varied levels of sperm competition. A recent study using this model identified positive selection and coevolution between Izumo1 on sperm and CD9 on the egg across the Mus genus [ 7 ]. The influence of sexual selection on the evolution of a protein pair can be examined by comparing lineage-specific ω values (an indicator of selective pressure) to a proxy of sexual selection (e.g.…”

“…relative testes mass). This method produced negative results for CD9 and Izumo1, but could be applied to Juno and Izumo1 in the future [ 7 ].…”

“…Mammalia), it is important to note that they often overlook lineage-specific or recent bouts of selection, and can be biased based on the sequenced taxa that are currently available [ 45 , 46 ]. For example, Izumo1 is reportedly evolving under positive selection in Mus , despite appearing to be under the influence of purifying selection in Glires [ 7 ]. In other instances, the coarse signals identified by analysing previously sequenced species remain unchanged with the addition of new closely related species.…”

Comparative Sperm Proteomics in Mouse Species with Divergent Mating Systems

“…This includes proteins that are known to mediate sperm-zona pellucida interactions (ZAN, ZP3R, ZPBP1 and 2), acrosome biogenesis (MAN2B2), acrosomal dynamics (CD46 and ZPBP2) and sperm–egg fusion (ADAM3). As might be expected given the codiversification of male and female interacting partners (Clark et al 2009; Claw et al 2014; Vicens and Roldan 2014), several of these proteins (ZAN, ZPBP1 and 2) also exhibit patterns of evolution consistent with the influence of positive selection. It is therefore plausible that fertilization efficiency could be modulated through changes in expression and developmental incorporation of sperm components responsible for gamete interactions, in conjunction with adaptive molecular evolution of these proteins.…”

Peer Review #3 of "Positive selection on human gamete-recognition genes (v0.2)"

“…Proteins expressed on the surfaces of gametes mediate several types of cellular interactions at the time of fertilization, including chemoattraction of swimming sperm towards the egg, sperm binding to the egg extracellular coat, lysis or dissolution of the egg coat, and fusion of the gamete plasma membranes. Because those interactions may directly affect reproductive success, the genes encoding such proteins are sensitive to selection and often show evidence of diversifying or positive selection leading to high rates of amino acid substitution (Swanson et al 2001; Swanson and Vacquier 2002;Hamm et al 2007;Clark et al 2009;Vicens and Roldan 2014). Different adaptive solutions to selection acting on variation in gamete attraction, binding, or fusion can lead to significant population differentiation within species (e.g., Hart et al 2014), and are implicated in the origin or maintenance of reproductive isolation between species (Coyne and Orr 2004;Palumbi 2009;Lessios 2011;Gavrilets 2014).…”