# Inbreeding does not reduce major histocompatibility complex diversity in the banded mongoose

## TL;DR

This study shows that inbreeding in banded mongooses does not reduce MHC diversity, which is important for immune function and conservation genetics.

## Contribution

The study is the first to characterize both MHC classes in a social, wild carnivore using high-throughput sequencing and a large sample size.

## Key findings

- Banded mongooses show MHC diversity comparable to other carnivores despite frequent inbreeding.
- MHC-I exon 2 shows higher diversity and stronger diversifying selection compared to exon 3.
- Nonclassical MHC-I sequences exhibit trans-species polymorphism and species-specific gene duplication.

## Abstract

The major histocompatibility complex’s (MHC) role in the vertebrate adaptive immune response and its exceptional polymorphism make it a key target for studying adaptive gene evolution. However, studies on carnivore MHC often focus on populations with severe bottlenecks or conservation concerns, leading to small sample sizes and unreliable generalizations about MHC diversity. Furthermore, many studies focus on one MHC class and do not cover the whole peptide binding groove of the MHC molecule. Here, we characterize MHC class I (MHC-I) exon 2 and 3, encoding the α1- and α2-domains, as well as MHC-II DRB exon 2 for a large sample (N = 285–384) of a wild carnivore of least conservation concern but with high levels of inbreeding, the banded mongoose.

MHC-I showed higher allelic and supertype diversity and polymorphism compared to MHC-II, consistent with findings in humans where MHC-I experiences stronger diversifying selection. MHC-I exon 3 exhibited the lowest diversity, likely due to its specific role in forming the peptide binding groove. Diversifying selection was stronger on MHC-I exon 2 (α1 domain) than exon 3 (α2 domain). Despite frequent inbreeding, banded mongooses showed MHC diversity comparable to other carnivores of least concern using phylogenetic mixed models. Phylogenetic analysis indicated a longer evolutionary trajectory for MHC-II compared to MHC-I and species-specific gene duplication of nonclassical MHC-I sequences clustering with classical sequences. Trans-species polymorphism in nonclassical MHC-I sequences suggested homology or convergent evolution.

This study is the first to characterize both MHC classes of a social, wild carnivore using high-throughput sequencing and a large sample size. Despite frequent inbreeding, banded mongooses exhibit MHC diversity comparable to other carnivores of least conservation concern, challenging assumptions that inbreeding universally reduces genetic diversity. Higher diversity and selection on MHC-I exon 2 emphasize its role in immune defense, while lower diversity in exon 3 highlights functional divergence between the exons. The longer evolutionary trajectory of MHC-II reveals differences in dynamics between MHC classes. Species-specific gene duplication and trans-species polymorphism in nonclassical MHC-I sequences suggest complex evolutionary mechanisms. These findings advance understanding of MHC evolution in wild carnivores, with implications for conservation genetics, particularly regarding the effects of social structure and inbreeding on immune gene diversity.

The online version contains supplementary material available at 10.1186/s12862-025-02456-x.