Rodriguez-Valbuena, H. | bioRxiv Science

bioRxiv2024

Genetic and functional diversity of allorecognition receptors in the urochordate, Botryllus schlosseri

Allorecognition in Botryllus schlosseri is controlled by a highly polymorphic locus (the fuhc), and functionally similar to missing-self recognition utilized by Natural Killer cells-compatibility is determined by sharing a self-allele, and integration of activating and inhibitory signals determines outcome. We had found these signals were generated by two fuhc-encoded receptors, called fester and uncle fester. Here we show that fester genes are members of an extended family consisting of >37 loci, and co-expressed with an even more diverse gene family-the fester co-receptors (FcoR). The FcoRs are membrane proteins related to fester, but include conserved tyrosine motifs, including ITIMs and hemITAMs. Both genes are encoded in highly polymorphic haplotypes on multiple chromosomes, revealing an unparalleled level of diversity of innate receptors. Our results also suggest that ITAM/ITIM signal integration is a deeply conserved mechanism that has allowed convergent evolution of innate and adaptive cell-based recognition systems.

immunology↗

bioRxiv2022

Multiple alr genes exhibit allorecognition-associated variation in the colonial cnidarian Hydractinia

The genetics of allorecognition has been determined from inbred lines of Hydractinia symbiolongicarpus, in which genetic control is attributed mainly to the highly polymorphic loci allorecognition 1 (alr1) and allorecognition 2 (alr2) located within the Allorecognition Complex (ARC). While allelic variation at alr1 and alr2 can predict the phenotypes in inbred lines, these two loci do not entirely predict the allorecognition phenotypes in wild-type colonies and their progeny, suggesting the presence of additional uncharacterized genes that improve the prediction of these phenotypes. Comparative genomics analyses were used to identify coding sequence differences in assembled chromosomal intervals of the ARC and genomic scaffold sequences between two incompatible H. symbiolongicarpus siblings from a backcross population. New IgSF-like genes are reported for the ARC, five of these genes are closely related to the alr1 and alr2 genes, suggesting the presence of multiple alr-type genes within this complex. Cloning evidence revealed that the allelic polymorphism of eight Ig-SF-like genes is associated with allorecognition phenotypes in a backcross population of H. symbiolongicarpus. Remarkably, alternative splicing was found as a mechanism that contributes to the functional variability of these genes by changing putative activating receptors to inhibitory receptors, or generating secreted isoforms of allorecognition proteins. Our findings demonstrate that allorecognition in H. symbiolongicarpus is a multigenic phenomenon controlled by genetic variation in at least eight genes in the ARC complex, as well as putative uncharacterized variation outside of this region.

immunology↗