Class I MHC genes present in different species.

The primate evolutionary tree (Kuderna et al., 2023) is shown on the left hand side (nonprimate icons are shown in beige). The MHC region has been well characterized in only a handful of species; the rows corresponding to these species are highlighted in gray. Species that are not highlighted have partially characterized or completely uncharacterized MHC regions. Asterisks indicate new information provided by the present study, typically discovery of a gene’s presence in a species. Each column/color indicates an orthologous group of genes, labeled at the top and ordered as they are in the human genome (note that not all genes appear on every haplotype). A symbol indicates that a given gene is present in a given species; when a species has 3 or more paralogs of a given gene, only 3 symbols are shown for visualization purposes. Filled symbols indicate that the gene is fixed in that species, outlined symbols indicate that the gene is unfixed, and semi-transparent symbols indicate that the gene’s fixedness is not known. The shape of the symbol indicates the gene’s role, either a pseudogene, classical MHC gene, non-classical MHC gene, a gene that shares both features (“dual characteristics”), or unknown. The horizontal gray brackets indicate a breakdown of 1:1 orthology, where genes below the bracket are orthologous to 2 or more separate loci above the bracket. The set of two adjacent gray brackets in the top center of the figure show a block duplication. Gene labels in the middle of the plot (“W”, “A”, “G”, “B”, and “I”) clarify genes that are named differently in different species. OWM, Old-World Monkeys; NWM, New World Monkeys.

Class II MHC genes present in different species.

The mammal evolutionary tree is shown on the left hand side, with an emphasis on the primates (Foley et al., 2023; Kuderna et al., 2023). The rest of the figure design follows that of Figure 1, except that we did not need to limit the number of symbols shown per locus/species due to space constraints. OWM, Old-World Monkeys; NWM, New World Monkeys; Strep., Strepsirrhini.

The Class I exon 4 multi-gene BEAST2 tree.

The Class I multi-gene tree was constructed using exon 4 (non-PBR) sequences from Class I genes spanning the primates. A) For the purposes of visualization, each clade in the multi-gene tree is collapsed and labeled according to the main species group and gene content of the clade. The white labels on colored rectangles indicate the species group of origin, while the colored text to the right of each rectangle indicates the gene name. The abbreviations are defined in the species key to the right. B) The expanded MHC-F clade (corresponding to the clade in panel A marked by a †). C) The expanded NWM MHC-G clade (marked by a ∗ in panel A). In panels B and C, each tip represents a sequence and is labeled with the species of origin (white label on colored rectangle) and the sequence ID or allele name (colored text to the right of each rectangle; see Appendix 2). The species key is on the right hand side of panel A. Dashed branches have been shrunk to 10% of their original length (to clarify detail in the rest of the tree at this scale). OWM: old-world monkeys; NWM: new-world monkeys; Cat.: Catarrhini—apes and OWM; Pri.: Primates—apes, OWM and NWM; Mam.: mammals—primates and other outgroup mammals.

The Class II exon 3 multi-gene BEAST2 trees.

The trees were constructed using all Class IIA and all Class IIB exon 3 (non-PBR) sequences across all available species. The design of this figure follows Figure 3. A) The top tree shows the collapsed Class IIA gene tree, while the bottom tree shows the collapsed Class IIB gene tree. In this case, all collapsed clades are labeled with “Mam.” for mammals, because sequences from primates and mammal outgroups assort together by gene. B) The expanded MHC-DPA clade (corresponding to the clade in panel A marked by a ∗). C) The expanded MHC-DPB clade (marked by a † in panel A). D) The expanded MHC-DRB clade (marked by a § in panel A). OWM: old-world monkeys; NWM: new-world monkeys; Cat.: Catarrhini—apes and OWM; Mam.: mammals—primates and other outgroup mammals.

Class I α-block-focused multi-gene BEAST2 trees.

The α-block-focused trees use the common backbone sequences as well as additional sequences from our custom BLAST search of available reference genomes. For the purposes of visualization, some clades are collapsed and labeled with the species group and gene content of the clade (colored text to the right of each rectangle). The white labels on colored rectangles indicate the species group of origin, while the colored text to the right of each rectangle indicates the gene or sequence name (see Appendix 2). The species abbreviations are defined in the species key at the bottom. A) Exon 3 α-block-focused BEAST2 tree with expanded MHC-V clade. B) The expanded MHC-A/AL/OKO/U/Y clade from the exon 3 tree (corresponding to the clade in panel A marked by a ∗), focusing on MHC-U. C) Exon 4 α-block-focused BEAST2 tree with expanded MHC-K/KL clade. D) The expanded MHC-W/WL/P/T/TL/OLI clade from the exon 4 tree (marked by a † in panel C). OWM: old-world monkeys; NWM: new-world monkeys; Cat.: Catarrhini—apes and OWM; Pri.: Primates—apes, OWM and NWM.

Evolution of the Class I α-block.

The primate evolutionary tree is shown in gray (branches not to scale). The bottom of the tree shows currently known haplotypes in each species or species group. Horizontal gray bars indicate haplotypes shared among the African apes. The history of the genes/haplotypes in the α-block is overlaid on the tree, synthesizing previous work with our own observations (see Methods, Figure 8, and Appendix 3 for explanations and citations). Genes are represented by colored rectangles, while haplotypes are shown as horizontal lines containing genes. MHC-F—indicating the telomeric end of the α-block—was fixed early on and is located immediately to the left on all haplotypes shown, but is not pictured due to space constraints. Dashed arrows with descriptive labels represent evolutionary events. In the upper right, the “Symbol Key” explains the icons and labels. The “Gene Relationships” panel shows the relationships between the loci shown on the tree, without the layered complexity of haplotypes and speciation events. The “MHC-A Allelic Lineages” panel shows which MHC-A allele groups are present in human, chimpanzee, and gorilla.

Evolution of MHC-DRB.

The bottom of the tree shows current haplotypes in each species or species group; human, chimpanzee, gorilla, and old-world monkey haplotypes are well characterized, while orangutan, gibbon, and new-world monkey haplotypes are partially known. The history of the genes/haplotypes in the MHC-DRB region is overlaid on the tree, synthesizing previous work with our own observations (see Methods and Figure 8). The rest of the figure design follows that of Figure 6.

GenBank accession numbers for reference genomes used in this study. Accessions point to the MHC-containing chromosome (or partial chromosome) from each genome.

BEAST2 trees provide insight into MHC gene and allele relationships.

We first created multi-gene Bayesian phylogenetic trees using sequences from all genes and species, separated into Class I, Class IIA, and Class IIB groups. We then focused on various subtrees of the multi-gene trees by adding more sequences for each subtree and running BEAST2 using only sequences from that group (in addition to the “backbone” sequences common to all trees). Our trees gave us insight into both overall gene relationships (this paper) and allele relationships within gene groups (see our companion paper, Fortier and Pritchard (2025)).

Class I and Class II differ in their mechanism of peptide presentation.

For Class I (left), endogenous proteins are broken down by a proteasome and imported into the endoplasmic reticulum (ER), where they are loaded onto an awaiting MHC molecule. The peptide-bound MHC molecule is then transported to the cell surface via the Golgi, where it can interact with the T cell receptor (TCR) of a CD8+ T cell (Neefjes et al., 2011). The Class II pathway (right) is more complex. Here, exogenous proteins are endocytosed and broken down on their way to the MHC class II compartment (MIIC). MHC molecules originate in the ER, where they are loaded with the invariant chain (Ii). The Ii-bound MHC molecule is transported to the MIIC, where the Ii is trimmed and swapped out for a endocytosed peptide. This swap is catalyzed by the non-classical MHC molecule MHC-DM (Neefjes et al., 2011; Dijkstra and Yamaguchi, 2019; Schulze and Wucherpfennig, 2012). The peptide-bound MHC molecule can then be transported to the cell surface to interact with the T cell receptor (TCR) of a CD4+ T cell (Neefjes et al., 2011). Throughout the figure, solid lines indicate labels while dashed lines indicate movement or processes.

MHC allele nomenclature.

A) Human HLA alleles are named in a standard fashion, with the gene name followed by four colon-separated fields. The first field indicates a broad-scale allele group which sometimes corresponds to a serological antigen. The second field denotes a specific HLA protein. The third field indicates synonymous changes to the nucleotide sequence in the coding region, while the fourth field is used to distinguish alleles with differences in the noncoding regions. If an allele’s expression has been characterized, an informative suffix is sometimes added (Robinson et al., 2024; Marsh et al., 2010). B) Researchers have applied the same format to non-human alleles, with some key differences. Instead of “HLA”, a prefix which concatenates the first two letters of the genus name with the first two letters of the species name is used, except in certain cases where the species’ MHC system was named long ago. Paralogs can be distinguished using numbers, but sequences unassigned to a particular locus or paralog might incorporate a ‘W’ in the gene name. Use of expression tags varies, with some being added to the end of the gene name instead of the end of the entire allele name. Pseudogenes can be denoted with a “p” or “Ps” in the gene name suffixes, gene names themselves, expression suffixes, or not at all. For both human and non-human alleles, the lack of an expression suffix does not imply normal expression (de Groot et al., 2020). SLA: Swine Leukocyte Antigen; Chsa: Chlorocebus sabaeus—green monkey; Lero: Leontopithecus rosalia—golden lion tamarin; Mamu: Macaca mulatta—rhesus macaque; Aotr: Aotus trivirgatus—three-striped night monkey; Popy: Pongo pygmaeus—Bornean orangutan; Ceat: Cercocebus atys—sooty mangabey; Sala: Saguinus labiatus—white-lipped tamarin; Gogo: Gorilla gorilla—Western gorilla; Rano: Rattus norvegicus—brown rat; Patr: Pan troglodytes—chimpanzee; Papa: Pan paniscus—bonobo.

Class I MHC genes present in different species (without asterisks).

The primate evolutionary tree (Kuderna et al., 2023) is shown on the left hand side (non-primate icons are shown in beige). The MHC region has been well characterized in only a handful of species; the rows corresponding to these species are highlighted in gray. Species that are not highlighted have partially characterized or completely uncharacterized MHC regions. Each column/color indicates an orthologous group of genes, labeled at the top and ordered as they are in the human genome (note that not all genes appear on every haplotype). A symbol indicates that a given gene is present in a given species; when a species has 3 or more paralogs of a given gene, only 3 symbols are shown for visualization purposes. Filled symbols indicate that the gene is fixed in that species, outlined symbols indicate that the gene is unfixed, and semi-transparent symbols indicate that the gene’s fixedness is not known. The shape of the symbol indicates the gene’s role, either a pseudogene, classical MHC gene, non-classical MHC gene, a gene that shares both features (“dual characteristics”), or unknown. The horizontal gray brackets indicate a breakdown of 1:1 orthology, where genes below the bracket are orthologous to 2 or more separate loci above the bracket. The set of two adjacent gray brackets in the top center of the figure show a block duplication. Gene labels in the middle of the plot (“W”, “A”, “G”, “B”, and “I”) clarify genes that are named differently in different species. OWM, Old-World Monkeys; NWM, New World Monkeys.

BLAST hits for MHC Class I genes in various reference genomes.

On the left hand side is the species tree relating the species used in this study (Kuderna et al., 2023). Next to each species is a diagram of the chromosome where theMHCresides; theMHCClass I region is indicated in black. The right hand side shows an expanded view of the Class I region in each species, with the location of the stretch indicated in gigabases from the start of the reference chromosome. Although the MHC region is located in a slightly different place in each genome, the gray lines are scaled the same way–in other words, an equivalent distance along the line in two different species spans the same number of bases. Genes were annotated using a custom BLAST search against IPD database alleles and are colored by gene identity (see Methods). The human genes (top) are also labeled. OWM, Old-World Monkeys; NWM, New World Monkeys.

Class II MHC genes present in different species (without asterisks).

The mammal evolutionary tree is shown on the left hand side, with an emphasis on the primates (Foley et al., 2023; Kuderna et al., 2023). The MHC region has been well characterized in only a handful of species; the rows corresponding to these species are highlighted in gray. Species that are not highlighted have partially characterized or completely uncharacterized MHC regions. Each column/color indicates an orthologous group of genes, labeled at the top and ordered as they are in the human genome (note that not all genes appear on every haplotype). A symbol indicates that a given gene is present in a given species. Filled symbols indicate that the gene is fixed in that species, outlined symbols indicate that the gene is unfixed, and semi-transparent symbols indicate that the gene’s fixedness is not known. The shape of the symbol indicates the gene’s role, either a pseudogene, classical MHC gene, non-classical MHC gene, a gene that shares both features (“dual characteristics”), or unknown. The horizontal gray brackets indicate a breakdown of 1:1 orthology, where genes below the bracket are orthologous to 2 or more separate loci above the bracket. OWM, Old-World Monkeys; NWM, New World Monkeys; Strep., Strepsirrhini.

BLAST hits for MHC Class II genes in various reference genomes.

On the left hand side is the species tree relating the species used in this study (Kuderna et al., 2023). Next to each species is a diagram of the chromosome where the MHC resides; the MHC Class II region is indicated in black. The right hand side shows an expanded view of the Class II region in each species, with the location of the stretch indicated in gigabases from the start of the reference chromosome. Although the MHC region is located in a slightly different place in each genome, the gray lines are scaled the same way—in other words, an equivalent distance along the line in two different species spans the same number of bases. Genes were annotated using a custom BLAST search against IPD database alleles and are colored by gene identity (see Methods). The human genes (top) are also labeled. OWM, Old-World Monkeys; NWM, New World Monkeys; Str., Strepsirrhini

Color and abbreviation key/tree for all species included in this study.

On the left hand side is the species tree relating the species used in this study (Kuderna et al., 2023; Foley et al., 2023). Each species/tip is labeled with a unique color and 4-letter abbreviation, which is composed of the first two letters of the genus name and first two letters of the species name. The common name and Latin name for each species are shown on the right hand side. Plecturocebus moloch is listed in the IPD-MHC database under its old name, Callicebus moloch, and uses a different abbreviation (Camo) in that resource. Similarly, Leontocebus fuscicolis was formerly known as Saguinus fuscicollis (Safu) in the IPD-MHC database. There appears to be some debate as to whether the pygmy marmoset should be placed in the Callithrix or Cebuella genus, but we have used the name Cebuella pygmaea (Cepy) in accordance with a recent primate study (Kuderna et al., 2023). This species is known as Callithrix pygmaea (Capy) in IPD-MHC. OWM, Old-World Monkeys; NWM, New World Monkeys; Str., Strepsirrhini; Rod., Rodentia; Lau., Laurasiatheria; Atl., Atlantogenata.

Full, non-collapsed versions of the Class I multi-gene BEAST2 trees.

A) Exon 2 tree (PBR-encoding). B) Exon 3 tree (PBR-encoding). C) Exon 4 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the MHC-A-related focused BEAST2 trees.

A) Exon 2 tree (PBR-encoding). B) Exon 3 tree (PBR-encoding). C) Exon 4 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the MHC-B-related focused BEAST2 trees.

A) Exon 2 tree (PBRencoding). B) Exon 3 tree (PBR-encoding). C) Exon 4 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the MHC-C-related focused BEAST2 trees.

A) Exon 2 tree (PBRencoding). B) Exon 3 tree (PBR-encoding). C) Exon 4 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the MHC-E-related focused BEAST2 trees.

A) Exon 2 tree (PBRencoding). B) Exon 3 tree (PBR-encoding). C) Exon 4 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the MHC-F-related focused BEAST2 trees.

A) Exon 2 tree (PBRencoding). B) Exon 3 tree (PBR-encoding). C) Exon 4 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the MHC-G-related focused BEAST2 trees.

A) Exon 2 tree (PBRencoding). B) Exon 3 tree (PBR-encoding). C) Exon 4 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the Class IIA multi-gene BEAST2 trees.

A) Exon 2 tree (PBRencoding). B) Exon 3 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the Class IIB multi-gene BEAST2 trees.

A) Exon 2 tree (PBRencoding). B) Exon 3 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the MHC-DRA focused BEAST2 trees.

A) Exon 2 tree (PBRencoding). B) Exon 3 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the MHC-DQA focused BEAST2 trees.

A) Exon 2 tree (PBRencoding). B) Exon 3 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the MHC-DPA focused BEAST2 trees.

A) Exon 2 tree (PBRencoding). B) Exon 3 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the MHC-DMA focused BEAST2 trees.

A) Exon 2 tree (PBRencoding). B) Exon 3 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the MHC-DOA focused BEAST2 trees.

A) Exon 2 tree (PBRencoding). B) Exon 3 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the MHC-DRB focused BEAST2 trees.

A) Exon 2 tree (PBRencoding). B) Exon 3 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the MHC-DQB focused BEAST2 trees.

A) Exon 2 tree (PBRencoding). B) Exon 3 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the MHC-DPB focused BEAST2 trees.

A) Exon 2 tree (PBRencoding). B) Exon 3 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the MHC-DMB focused BEAST2 trees.

A) Exon 2 tree (PBRencoding). B) Exon 3 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the MHC-DOB focused BEAST2 trees.

A) Exon 2 tree (PBRencoding). B) Exon 3 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the Class I α-block pseudogene-focused BEAST2 trees.

A) Exon 2 tree (PBR-encoding). B) Exon 3 tree (PBR-encoding). C) Exon 4 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Full, non-collapsed versions of the all-pseudogene-focused BEAST2 trees.

A) Exon 2 tree (PBR-encoding). B) Exon 3 tree (PBR-encoding). C) Exon 4 tree (non-PBR-encoding). Each tip represents a sequence, with the colored rectangle and four-letter abbreviation indicating the species. Following the rectangle, tips are labeled with the sequence name; sequences which have been assigned to loci are colored according to the gene group, while unassigned sequences are written in gray. Dashed branches are shortened to 10% of their length to expand detail in the rest of the tree.

Evolution of the Class I α-block (with references).

The bottom of the tree shows currently known haplotypes in each species or species group. Horizontal gray bars indicate haplotypes shared among the African apes. The history of the genes/haplotypes in the α-block is overlaid on the tree, synthesizing previous work with our own observations (see Methods and Figure 8). Genes are represented by colored rectangles, while haplotypes are shown as horizontal lines containing genes. MHC-F—indicating the telomeric end of the α-block—was fixed early on and is located immediately to the left on all haplotypes shown, but is not pictured due to space constraints. Dashed arrows with descriptive labels represent evolutionary events. In the upper right, the “Symbol Key” explains the icons and labels. The “Gene Relationships” panel shows the relationships between the loci shown on the tree, without the layered complexity of haplotypes and speciation events. The “MHC-A Allelic Lineages” panel shows which MHC-A allele groups are present in human, chimpanzee, and gorilla. Numbers in black boxes indicate references, with the key shown at the left; each is placed on the parts of the figure where it is relevant.

Evolution of the MHC-DRB region (with references).

The primate evolutionary tree is shown in gray (branches not to scale). The bottom of the tree shows current haplotypes in each species or species group; human, chimpanzee, gorilla, and old-world monkey haplotypes are well characterized, while orangutan, gibbon, and new-world monkey haplotypes are partially known. The history of the MHC-DRB genes and allelic lineages is overlaid on the tree, synthesizing previous work with our own observations (see Methods and Figure 8). Genes are represented by colored rectangles, while haplotypes are shown as horizontal lines containing genes. Dashed arrows with descriptive labels represent evolutionary events. The upper right “Symbol Key” explains the icons and labels. The “Gene Relationships” panel shows the evolution of the loci without the complexity of haplotypes and speciation events that is shown on the main tree. The “DRB1 Allelic Lineages” panel defines our lineage labels along with the allele groups that are present and orthologous in human, chimp, and gorilla. Numbers in black boxes indicate references, with the key shown at the left; each is placed on the parts of the figure where it is relevant.