Structure and evolution of the squamate major histocompatibility complex as revealed by two Anolis lizard genomes

Abstract

The major histocompatibility complex (MHC) is an important genomic region for adaptive immunity and has long been studied in ecological and evolutionary contexts, such as disease resistance and mate and kin selection. The MHC has been investigated extensively in mammals and birds but far less so in squamate reptiles, the third major radiation of amniotes. We localized the core MHC genomic region in two squamate species, the green anole (Anolis carolinensis) and brown anole (A. sagrei), and provide the first detailed characterization of the squamate MHC, including the presence and ordering of known MHC genes in these species and comparative assessments of genomic structure and composition in MHC regions. We find that the Anolis MHC, located on chromosome 2 in both species, contains homologs of many previously-identified mammalian MHC genes in a single core MHC region. The repetitive element composition in anole MHC regions was similar to those observed in mammals but had important distinctions, such as higher proportions of DNA transposons. Moreover, longer introns and intergenic regions result in a much larger squamate MHC region (11.7 Mb and 24.6 Mb in the green and brown anole, respectively). Evolutionary analyses of MHC homologs of anoles and other representative amniotes uncovered generally monophyletic relationships between species-specific homologs and a loss of the peptide-binding domain exon 2 in one of two mhc2β gene homologs of each anole species. Signals of diversifying selection in each anole species was evident across codons of mhc1, many of which appear functionally relevant given known structures of this protein from the green anole, chicken, and human. Altogether, our investigation fills a major gap in understanding of amniote MHC diversity and evolution and provides an important foundation for future squamate-specific or vertebrate-wide investigations of the MHC.

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

“…We took the published MHC gene arrangement of three other reptiles to compare if the gene arrangement is conserved among all reptiles (Step 3.1 in Figure 1). The references used were saltwater crocodile (Jaratlerdsiri et al, 2014a), tuatara (Miller et al, 2015), Komodo Dragon (Reed and Settlage, 2021), and green anole (Card et al, 2022). We used the tree constructed using VertLife 3 (Tonini et al, 2016) to describe the phylogenetic distribution of these four species.…”

“…Phylogenetic evolution of MHC-I genes in (B) Chinese Alligator, (C) in reptiles using the whole CDS, and (D) in reptiles using the antigen-presenting exon 2. Explanatory notes are the same as in dragon (Reed and Settlage, 2021), and two anoles (Card et al, 2022)], Tap2 with MHC-I (saltwater crocodile), and MHC-I and MHC-II genes were not far away from each other (tuatara and anoles). These findings were just part of the story.…”

“…Knowledge of the complete MHC architecture in all tetrapod lineages can help us answer the above mentioned questions. To our knowledge, research on non-avian reptiles' MHC regions has been conducted on saltwater crocodile (Crocodylus porosus) (Jaratlerdsiri et al, 2014a), tuatara (Sphenodon punctatus) (Miller et al, 2015), Komodo dragon (Varanus komodoensis) (Reed and Settlage, 2021), and two anoles (Anolis carolinensis and Anolis sagrei) (Card et al, 2022). However, these studies have not sufficiently explored the genomic organization of reptiles.…”

“…Based on genome data, multiple Class Iα and Class IIβ genes were observed in Komodo dragon (in the Squamata clade), but most were alone, without any other linked genes (Reed and Settlage, 2021). The latest reported core MHC genomic region in two Anolis lizards (in the Squamata clade) provided the first detailed characterization of reptiles' MHC, with a single core MHC region (Card et al, 2022). Although some TGS-based genomes of reptiles have been published, the complex MHC region cannot be easily illustrated, e.g., 56 MHC genes spanning 13 scaffolds were identified in tuatara's genome (Gemmell et al, 2020), and the detail MHC gene maps of Anolis were obtained using two independent datasets and approaches (BAC screening and sequencing and BLAST-derived inference of homology from genome) (Card et al, 2022).…”

“…The latest reported core MHC genomic region in two Anolis lizards (in the Squamata clade) provided the first detailed characterization of reptiles' MHC, with a single core MHC region (Card et al, 2022). Although some TGS-based genomes of reptiles have been published, the complex MHC region cannot be easily illustrated, e.g., 56 MHC genes spanning 13 scaffolds were identified in tuatara's genome (Gemmell et al, 2020), and the detail MHC gene maps of Anolis were obtained using two independent datasets and approaches (BAC screening and sequencing and BLAST-derived inference of homology from genome) (Card et al, 2022). This limited and fragmented information on Crocodylia clade's MHC region thus far does not allow the comparison of gene gain and loss and gene rearrangement in this lineage.…”