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MAIA, Fc receptor-like 3, supersedes JUNO as IZUMO1 receptor during human fertilization.

ABSTRACT: Gamete fusion is a critical event of mammalian fertilization. A random one-bead one-compound combinatorial peptide library represented synthetic human egg mimics and identified a previously unidentified ligand as Fc receptor-like 3, named MAIA after the mythological goddess intertwined with JUNO. This immunoglobulin super family receptor was expressed on human oolemma and played a major role during sperm-egg adhesion and fusion. MAIA forms a highly stable interaction with the known IZUMO1/JUNO sperm-egg complex, permitting specific gamete fusion. The complexity of the MAIA isotype may offer a cryptic sexual selection mechanism to avoid genetic incompatibility and achieve favorable fitness outcomes.

SUBMITTER: Vondrakova J

PROVIDER: S-EPMC9451160 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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MAIA, Fc receptor-like 3, supersedes JUNO as IZUMO1 receptor during human fertilization.

Vondrakova Jana J Frolikova Michaela M Ded Lukas L Cerny Jiri J Postlerova Pavla P Palenikova Veronika V Simonik Ondrej O Nahacka Zuzana Z Basus Krystof K Valaskova Eliska E Machan Radek R Pacey Allan A Holubcova Zuzana Z Koubek Pavel P Ezrova Zuzana Z Park Soojin S Liu Ruiwu R Partha Raghavendran R Clark Nathan N Neuzil Jiri J Ikawa Masahito M Erickson Kent K Lam Kit S KS Moore Harry H Komrskova Katerina K

Science advances 20220907 36

Gamete fusion is a critical event of mammalian fertilization. A random one-bead one-compound combinatorial peptide library represented synthetic human egg mimics and identified a previously unidentified ligand as Fc receptor-like 3, named MAIA after the mythological goddess intertwined with JUNO. This immunoglobulin super family receptor was expressed on human <i>oolemma</i> and played a major role during sperm-egg adhesion and fusion. MAIA forms a highly stable interaction with the known IZUMO1 ...[more]

PMID: 36070373

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Project description:Fertilization in mammals begins with the union of egg and sperm, an event that starts a cascade of cellular processes. The molecular-level understanding of these processes can guide the development of new strategies for controlling and/or promoting fertilization, and inform researchers and medical professional on the best choice of interventions. The proteins encoded by the IZUMO1 and JUNO genes form a ligand-receptor protein pair involved in the recognition of sperm and egg. Due to their role in the fertilization process, these proteins are potential targets for the development of novel anti-contraceptive, as well as infertility treatments. Here we present a comprehensive analysis of these gene sequences, with the objective of identifying evolutionary patterns that may support their relevance as targets for preventing or improving fertility among humans. JUNO and IZUMO1 gene sequences were identified within the genomes of over 2,000 humans sequenced in the 1000 Genomes Project. The human sequences were subjected to analyses of nucleotide diversity, deviation from neutrality of genetic variation, population-based differentiation (FST), haplotype inference, and whole chromosome scanning for signals of positive or of balancing selection. Derived alleles were determined by comparison to archaic hominin and other primate genomes. The potential effect of common non-synonymous variants on protein-protein interaction was also assessed. IZUMO1 displays higher variability among human individuals than JUNO. Genetic differentiation between continental population pairs was within whole-genome estimates for all but the JUNO gene in the African population group with respect to the other 4 population groups (American, East Asian, South Asian, and European). Tajima's D values demonstrated deviation from neutrality for both genes in comparison to a group of genes identified in the literature as under balancing or positive selection. Tajima's D for IZUMO1 aligns with values calculated for genes presumed to be under balancing selection, whereas JUNO's value aligned with genes presumed to be under positive selection. These inferences on selection are both supported by SNP density, nucleotide diversity and haplotype analysis. A JUNO haplotype carrying 3 derived alleles out of 5, one of which is a missense mutation implicated in polyspermy, was found to be significant in a population of African ancestry. Polyspermy has a disadvantageous impact on fertility and its presence in approximately 30% of the population of African ancestry may be associated to a potentially beneficial role of this haplotype. This role has not been established and may be related to a non-reproductive role of JUNO. The high degree of conservation of the JUNO sequence combined with a dominant haplotype across multiple population groups supports JUNO as a potential target for the development of contraceptive treatments. In addition to providing a detailed account of human genetic diversity across these 2 important and related genes, this study also provides a framework for large population-based studies investigating protein-protein interactions at the genome level.

Dataset Information

MAIA, Fc receptor-like 3, supersedes JUNO as IZUMO1 receptor during human fertilization.

Publications

MAIA, Fc receptor-like 3, supersedes JUNO as IZUMO1 receptor during human fertilization.

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