Herdegen-Radwan, M. | bioRxiv Science

bioRxiv2025

A key regulator of missing-self innate immunity is polymorphic and under diversifying selection

Host-parasite co-evolution drives the diversification of host immune genes involved in the recognition of pathogen antigens and molecular patterns. In contrast, the immune genes involved in self-recognition and inhibition of immune responses against self-cells (missing-self immunity) are expected to be evolutionarily constrained. However, many pathogens, such as the Lyme disease agent Borrelia, hijack these genes to evade the immune system and may therefore select for their diversification. How these contrasting but concurrent selective forces shape the evolution of missing-self regulators is not clearly understood. To fill this gap, we investigated polymorphism and molecular signatures of selection acting on a missing-self regulator, the Complement Factor H (CFH), in bank vole populations, which are an important wild reservoir for Borrelia. We then compared the geographic structuring in the CFH domain interacting with Borrelia (CCP 20) against a genomic background represented by RAD-seq markers. We found signals of positive and diversifying selection at CCP 20, suggesting that CFH evolved in response to pressures from pathogens. Additionally, we found other innate immunity genes within the alternative complement pathway, which is regulated by CFH, under diversifying selection, highlighting its involvement in host-parasite coevolution. This study demonstrates that an innate missing-self sensor in a wild vertebrate is under diversifying selection, likely driven by pathogens.

evolutionary biology↗

bioRxiv2024

Inbreeding depression depends on the body size and environmental conditions in a threatened songbird, the aquatic warbler Acrocephalus paludicola

While inbreeding is known to affect individual fitness and thus population extinction risk, studies have under-represented non-model species of conservation concern, and rarely sought conditionality of inbreeding depression. Here, using SNPs identified with RAD-seq, we determined inbreeding depression in a threatened bird, the aquatic warbler Acrocephalus paludicola, and whether its magnitude depends on phenotypic and environmental factors. We found that the inbreeding coefficient (F) of adults with small tarsi was negatively associated with the seasonal breeding success (in males) and clutch size (in females), with the respective decrease in fitness in the most inbred relative to the least inbred individuals of ~89% and ~12%. In contrast, in adult males, for the average tarsus, wing and mass, support was low for F to be related to the long-term return rate to breeding grounds. For mean phenotypic covariates and male density, we also found low evidence that F is associated with the annual breeding success. Likewise, there was little support that mother F is related to egg hatch success and nestling survival, and - for average phenotypic traits, rainfall, temperature and nest density, and accounting for breeding peak - to clutch and fledged brood sizes. For nestlings, animal models showed that F is more negatively related to tarsus under higher temperatures and its effect varies by study year. However, for average brood size, temperature, rainfall and prey abundance, and when controlling for nestling sex, breeding peak and mother F, evidence for nestling F and tarsus association was weak. We conclude that (1) inbreeding depression on fitness components is stronger in smaller-bodied individuals, (2) considering interaction with phenotypic and environmental variables enables more accurate estimation of inbreeding depression, and (3) the inbreeding depression estimates will inform extinction risk analysis and conservation actions for the aquatic warbler.

evolutionary biology↗