Co-evolution of the MHC class I and KIR gene families in rhesus macaques: ancestry and plasticity - PubMed (original) (raw)

Review

Co-evolution of the MHC class I and KIR gene families in rhesus macaques: ancestry and plasticity

Natasja G de Groot et al. Immunol Rev. 2015 Sep.

Abstract

Researchers dealing with the human leukocyte antigen (HLA) class I and killer immunoglobulin receptor (KIR) multi-gene families in humans are often wary of the complex and seemingly different situation that is encountered regarding these gene families in Old World monkeys. For the sake of comparison, the well-defined and thoroughly studied situation in humans has been taken as a reference. In macaques, both the major histocompatibility complex class I and KIR gene families are plastic entities that have experienced various rounds of expansion, contraction, and subsequent recombination processes. As a consequence, haplotypes in macaques display substantial diversity with regard to gene copy number variation. Additionally, for both multi-gene families, differential levels of polymorphism (allelic variation), and expression are observed as well. A comparative genetic approach has allowed us to answer questions related to ancestry, to shed light on unique adaptations of the species' immune system, and to provide insights into the genetic events and selective pressures that have shaped the range of these gene families.

Keywords: KIR; MHC; co-evolution; rhesus macaque.

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Figures

Figure 1

Schematic representation of Mamu‐A region configurations. The Mamu‐A1 gene is present on most region configurations but absent on # 11 and 12, and duplicated copies exist on configuration # 10. The A2 to A7 genes display a more restricted haplotype distribution, and most of them display differential transcription activity. Transcriptional activity is indicated as (+++) abundant, (++) moderate, and (+) low. The order and physical distance between the genes is only known for region configurations 1 and 5 18, 20.

Figure 2

Variability plot of different Mamu‐A gene products. Shown on the Y axis is the total number of different amino acids encountered at a given position. On the X axis are the α 1 and 2 domains, and the corresponding amino acids have been numbered sequentially. N represents the number of alleles that are encoded by the gene analyzed. The red and black dots indicate the contact residues in the B and F pocket, respectively.

Figure 3

The relationship between allelic heterogeneity and gene copy number variation for major histocompatibility complex (MHC) class I. Shown on the Y axis is an increasing scale depicting the number of alleles, whereas on the X axis an increasing scale in copy number variation per haplotype is shown. One extreme represents the situation in humans (one gene with a large amount of allelic variation), whereas rhesus macaques can be found on the other end of the spectrum (many region configurations but little allelic variation).

Figure 4

Overview of peptide‐binding motifs in rhesus macaques. Depicted are the Mamu‐A and Mamu‐B allotypes for which the peptide‐binding motifs are known and their similarity to

HLA

supertypes. Names in brackets refer to the allotype designations that were used previously. In a peptide‐binding motif, the conventional one‐letter code identifies the preferred, or in brackets the tolerated amino acid residues at the corresponding position. An asterisk ‘*’ identifies a secondary anchor position. References: a. 122, b. 123, c. 2, d. 124, e. 125, f. 126 g. 127, h. 128, i. 129, j. 130, k. 131, l. 132 m. 133, n. 134, o. 135, p. 136.

Figure 5

Killer immunoglobulin receptor (

KIR

) gene products in humans.

KIR

molecules span the membrane. The inhibiting molecules (L) have

ITIM

structures in common, whereas the potential activating structures (S) need to transfer their signaling via adapter molecules that possess

ITAM

structures. Although

KIR

4 pairs with an adapter molecule, it is often portrayed as an inhibitory receptor due to its

ITIM

structure.

ITAM

, immune receptor tyrosine‐based activation motifs;

ITIM

, immune receptor tyrosine‐based inhibitory motifs.

Figure 6

Neighbor‐joining tree depicting different killer immunoglobulin receptor (

KIR

) gene lineages. Intron 3 sequences were obtained from haplotypes that have been sequenced in humans (

), chimpanzees (Patr), orangutans (Popy), and rhesus macaques (Mamu), and were extracted from the

EMBL

database. Bootstrap values showing confidence levels above 50% have been indicated. The differently colored boxes represent

KIR

lineages I, II, III, and V.

Figure 7

Comparison of killer immunoglobulin receptor (

KIR

) gene organization in humans and rhesus macaques. The top panel shows the predicted ancestral

KIR

gene organization depicting its boundary genes (

LILR

and

FCAR

), as well as the four

KIR

lineages. The human and rhesus macaque

KIR

gene clusters have been aligned at the position of the framework gene

KIR

4 (lineage I: yellow box). The known ligands in humans are shown as well. The human

KIR

region shows expansion of lineage III at both the centromeric and telomeric region, whereas the rhesus macaques experienced expansion for lineage II at the telomeric region.

Figure 8

Killer immunoglobulin receptor (

KIR

) haplotypes in humans and rhesus macaques. The haplotypes in humans have been sequenced in detail, and the physical localization of the genes is known. For the rhesus macaque, this information is lacking, and therefore the rhesus macaque haplotypes have been inferred. For the human situation, the A and B, as well as their hybrid haplotypes (A/B and B/A), are shown. For the rhesus macaque, the haplotypes displaying gene copy number variation with regard to lineage II

KIR

genes are depicted.

Figure 9

Killer immunoglobulin receptor (

KIR

) gene distributions in macaques. Distribution of

KIR

loci in rhesus (Mamu) and cynomolgus (Mafa) macaques. For the rhesus macaque, individuals from India, Burma, and China have been analyzed. For the cynomolgus macaques, the origin of the animals is not precisely known. The color codes work as a heat‐map; black denotes absent and darker shades of the color indicate that more individuals possess the

KIR

gene moiety.

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Co-evolution of the MHC class I and KIR gene families in rhesus macaques: ancestry and plasticity - PubMed (original) (raw)