Massive introgression of major histocompatibility complex (MHC) genes in newt hybrid zones

Abstract

Variation in the vertebrate major histocompatibility complex (MHC) genes is crucial for fighting pathogen assault. Because new alleles confer a selective advantage, MHC should readily introgress between species, even under limited hybridization. Using replicated transects through two hybrid zones between strongly reproductively isolated European newts, Lissotriton montandoni and L. vulgaris, we demonstrated recent and ongoing MHC class I and II introgression in the Carpathian region. The extent of introgression correlated with the age of contact. In the older zone, MHC similarity between species within transects exceeded similarity between transects within species, implying pervasive introgression ‐ a massive exchange of MHC genes, not limited to specific variants. In simulations, the observed pattern emerged under the combined action of balancing selection and hybridization, but not when these processes acted separately. Thus, massive introgression at advanced stages of divergence can introduce novel and restore previously lost MHC variation, boosting the adaptive potential of hybridizing taxa. In consequence, MHC genes may be the last to stop introgressing between incipient species.

Differential introgression across newt hybrid zones: Evidence from replicated transects

“…It is thus possible that these genes do not currently introgress more easily, but it is also possible that introgression extended beyond the scale of our sampling, making its detection difficult with the use of cline analysis. Indeed, we found in the IN zone pervasive introgression of major histocompatibility complex (MHC) genes, a prime target of balancing selection, although cline parameters for MHC were not distinguishable from the genome‐wide Q cline (Dudek, Gaczorek, Zieliński, Babik, ). Overall, our data indicate that genes at the tails of the genome‐wide distribution of divergence between species only occasionally are found in the tails of the introgression—as predicted if processes other than introgression dominated the buildup of genomic differentiation between hybridizing species (Wolf & Ellegren, ).…”

Advances in the Evolutionary Understanding of MHC Polymorphism

“…In geographically structured models of host-pathogen coevolution (which do not consider MHC explicitly), polymorphism is maintained over longer periods than in unstructured models, probably due to asynchrony of coevolutionary interactions [52,53]. Introduction of MHC alleles from other species via adaptive introgression [4,55,92] could also lead to patterns consistent with TSP. Instead of being an indirect result of other dynamics, long-term coexistence of divergent allelic lineages could also be selected for directly, for example, due to their functional distinctness [33].…”

“…This antigen presentation is a crucial step in the adaptive immune response as it allows self/non-self discrimination by T cells, ultimately facilitating the recognition of infecting pathogens. The feature that distinguishes classical MHC genes (MHC genes hereafter) from other genes in the MHC region is their extreme polymorphism, with dozens to hundreds of allelic variants segregating in natural populations [3][4][5]. The polymorphism is most pronounced in the peptide-binding domain (PBD; see Glossary), in particular at peptidebinding sites (PBSs), amino-acid residues interacting directly with antigens [6].…”

Balancing selection, genetic drift, and human‐mediated introgression interplay to shape MHC (functional) diversity in Mediterranean brown trout

“…Noticeably, MHC-DAB richness (as well as STR richness) increased with increasing LDH-based admixture, thus supporting introgression as a non-negligible source of adaptive diversity in wild populations (Hedrick, 2013). Because adaptive genes undergoing balancing selection (RAA) are predicted to permeate into the gene pool of sink populations more readily than neutral ones (Schierup et al, 2000), introgression, even if limited, should be more pronounced for MHC than neutral markers (Dudek et al, 2019).…”

“…As an interesting consequence, the RAA may facilitate the introduction and spread of novel, initially rare alleles into populations via introgression. For instance, Dudek et al (2019) demonstrated that introgression coupled with balancing selection caused a massive allelic exchange and overall higher MHC variation in a newt hybrid zone.…”