Major histocompatibility complex genomic investigation of endangered Chinese alligator provides insights into the evolution of tetrapod major histocompatibility complex and survival of critically bottlenecked species

Abstract

BackgroundThe major histocompatibility complex (MHC) gene family, a vital immune gene family in vertebrates, helps animals defend against pathogens. The polymorphism of MHC genes is important for a species and is considered to be caused by the numerous alleles of MHC antigen-presenting genes. However, the mechanism of this process is unclear due to the lack of data on the MHC structure. The evolutionary trajectories of the tetrapod MHC are also unclear because of insufficient studies on the reptile MHC architecture. Here, we studied the Chinese alligator (Alligator sinensis), which experienced a population bottleneck, but the population increased rapidly in the past 30 years and is proposed to have a unique MHC system to face pathogenic challenges.ResultsWe successfully constructed a 2 Mb MHC region using bacterial artificial chromosome (BAC) library and genome data of the Chinese alligator and checked the antigen-presenting genes using transcriptome data and the rapid amplification of cDNA ends (RACE) technique. The MHC architecture reported here uncovers adjacent Class I and Class II subregions and a unique CD1 subregion. This newly added information suggested that the Class I-II structure pattern was more ancient in tetrapods and helped reconstruct the evolution of the MHC region architecture. We also found multiple groups of MHC class I (MHC-I) (12 duplicated loci, belonging to three groups, two of which were novel) and MHC class II (MHC-II) (11 duplicated loci, belonging to two groups) inside the 2 Mb MHC region, and there were three more duplicated MHC-I loci outside it. These highly duplicated antigen-presenting loci had differences in expression, amino acid length of antigen-presenting exons, and splice signal of exon and intron, which together promoted the polymorphism of duplicated genes. Although the MHC antigen-presenting genes were identified as monomorphic or oligomorphic in our previous population study, the loci with high copy numbers and many differences can make up for this loss, presenting another mechanism for polymorphism in antigen presentation. These MHC-I and MHC-IIB loci with low polymorphism for each locus, but high numbers in all, may also contribute to MHC antigen-presenting binding variability in a population.ConclusionTo summarize, the fine MHC region architecture of reptiles presented in this study completes the evolutionary trajectories of the MHC structure in tetrapods, and these distinctive MHC gene groups in the Chinese alligator may have helped this species to expand rapidly in the past recent years.

MHC Architecture in Amphibians—Ancestral Reconstruction, Gene Rearrangements, and Duplication Patterns

“…A relatively simple organization of the ancestral amphibian MHC was proposed previously based on the analysis of X. tropicalis MHC region ( Ohta et al 2006 ), while the data from birds ( He, Liang, et al 2022 ), reptiles ( Miller et al 2015 ; Card et al 2022 ; He, Zhu, et al 2022 ), and marsupial mammals ( Belov et al 2006 ) suggest that the simple architecture has generally been maintained throughout the evolutionary history of tetrapods. Major architectural changes, such as the apparent large-scale inversion ( Kaufman 2018 ) that inserted the class III region between class I and class II and broke the linkage between MHC-Ia and antigen-processing genes in eutherian mammals, or extreme expansions of classical MHC genes and translocations of MHC-IIA or TAP genes outside the core MHC, as seen in some birds ( He, Liang, et al 2022 ), were probably uncommon.…”

“…Research on the MHC region in nonavian reptiles has been conducted in several species (e.g., Komodo dragon Varanus komodoensis ( Reed and Settlage 2021 ), tuatara Sphenodon punctatus ( Miller et al 2015 ; Gemmell et al 2020 ), but information on its architecture is incomplete. Recently, genomic analyses of the MHC in two Anolis lizards ( Anolis carolinensis and Anolis sagrei ) ( Card et al 2022 ) and the Chinese alligator Alligator sinensis ( He, Zhu, et al 2022 ) provided a detailed characterization of reptile MHC, which contains a single-core MHC region with linked class I and class II subregions. An inversion of the class II subregion has also been reported in reptiles ( He, Zhu, et al 2022 ).…”

“…Recently, genomic analyses of the MHC in two Anolis lizards ( Anolis carolinensis and Anolis sagrei ) ( Card et al 2022 ) and the Chinese alligator Alligator sinensis ( He, Zhu, et al 2022 ) provided a detailed characterization of reptile MHC, which contains a single-core MHC region with linked class I and class II subregions. An inversion of the class II subregion has also been reported in reptiles ( He, Zhu, et al 2022 ).…”