Reconstructing Macroevolutionary Patterns in Avian MHC Architecture With Genomic Data

Abstract

The Major Histocompatibility Complex (MHC) is a hyper-polymorphic genomic region, which forms a part of the vertebrate adaptive immune system and is crucial for intra- and extra-cellular pathogen recognition (MHC-I and MHC-IIA/B, respectively). Although recent advancements in high-throughput sequencing methods sparked research on the MHC in non-model species, the evolutionary history of MHC gene structure is still poorly understood in birds. Here, to explore macroevolutionary patterns in the avian MHC architecture, we retrieved contigs with antigen-presenting MHC and MHC-related genes from available genomes based on third-generation sequencing. We identified: 1) an ancestral avian MHC architecture with compact size and tight linkage between MHC-I, MHC-IIA/IIB and MHC-related genes; 2) three major patterns of MHC-IIA/IIB unit organization in different avian lineages; and 3) lineage-specific gene translocation events (e.g., separation of the antigen-processing TAP genes from the MHC-I region in passerines), and 4) the presence of a single MHC-IIA gene copy in most taxa, showing evidence of strong purifying selection (low dN/dS ratio and low number of positively selected sites). Our study reveals long-term macroevolutionary patterns in the avian MHC architecture and provides the first evidence of important transitions in the genomic arrangement of the MHC region over the last 100 million years of bird evolution.

Keywords: MHC architecture; MHC gene structure; avian MHC; macroevolutionary; third-generation sequencing genome.

FIGURE 1

The protocol used to reconstruct the evolution of avian MHC structure.

FIGURE 2

The patterns of gene arrangement in (A) MHC class I-related, and (B) class II-related regions. *n indicates copy number variation of a single gene (MHC-I or MHC-IIB), while D with parentheses indicates duplication of a linked region. For MHC-I region, GalGal-like-V variant indicates duplicated (I × n ∼ TAP1∼TAP2∼I × n) unit, and Passer-like pattern indicates lack of linkage between TAPs and MHC-I genes. For MHC-II region, the NipNip-like pattern indicates a duplicated (IIB ∼ IIA) unit. The dashed box of COL11A2 indicates that this gene may be either present or absent in the MHC-II region.

FIGURE 3

The arrangement of MHC-I and MHC-II regions in 20 non-passerine bird species. The MHC-I- related region is marked with green, while MHC-II region including or excluding MHC-IIA gene is marked with purple and yellow, respectively. MHC-IIA is marked with blue, when not linked to the core MHC-II region. A single slash indicates the same contig or chromosome (numbers listed under the gene arrangement patterns indicate the total length of missing distances associated with single slashes), while a double slash indicates different contig or chromosome. The numbers marked with asterisks (above gene arrangement) indicate the distances that do not match the scale. Note: 1 Visualization of MHC structure for Anas platyrhynchos based on genome-2 in Table 1 (GCA_900411745.1), while the distance between MHC-I and MHC-II regions was 310 kb in genome-1 (GCA_015476345.1).

FIGURE 4

The arrangement of MHC-I, MHC-II, and TAP genes in eight passerine bird species. A single slash indicates the same contig or chromosome and associated numbers indicate the length of missing distances, while *number indicates the number of duplication events. A single slash indicates the same contig or chromosome (numbers listed under the gene arrangement patterns indicate the total length of missing distances associated with single slashes).

FIGURE 5

The predicted ancient MHC architecture in birds and its evolution in derived groups. Asterisks indicate characters that are unique to a group.