Reproduction, infection and killer-cell immunoglobulin-like receptor haplotype evolution.

Bridget S Penman,Sunetra Gupta,Olympe Chazara,Peter Parham,Ashley Moffett

doi:10.1007/s00251-016-0935-9

Bridget S Penman, Sunetra Gupta + Show 3 more

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https://doi.org/10.1007/s00251-016-0935-9

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Abstract

Killer-cell immunoglobulin-like receptors (KIRs) are encoded by one of the most polymorphic families in the human genome. KIRs are expressed on natural killer (NK) cells, which have dual roles: (1) in fighting infection and (2) in reproduction, regulating hemochorial placentation. Uniquely among primates, human KIR genes are arranged into two haplotypic combinations: KIR A and KIR B. It has been proposed that KIR A is specialized to fight infection, whilst KIR B evolved to help ensure successful reproduction. Here we demonstrate that a combination of infectious disease selection and reproductive selection can drive the evolution of KIR B-like haplotypes from a KIR A-like founder haplotype. Continued selection to survive and to reproduce maintains a balance between KIR A and KIR B.Electronic supplementary materialThe online version of this article (doi:10.1007/s00251-016-0935-9) contains supplementary material, which is available to authorized users.

Highlights

Killer-cell immunoglobulin-like receptors (KIRs) are expressed on the surface of natural killer cells (NK cells)— the major effector lymphocytes of innate immunity
We demonstrate that a combination of infectious disease selection and reproductive selection can drive the evolution of both KIR A—like and KIR B-like haplotypes from a KIR A-like ancestor
We found that a balanced scenario, where KIR A-like and KIR B-like haplotypes and C1 and C2 are all present after 15,000 generations, was impossible to obtain without assuming some degree of selection from HLA-evading pathogens (Fig. S2, parameter θ)

Summary

Introduction

Killer-cell immunoglobulin-like receptors (KIRs) are expressed on the surface of natural killer cells (NK cells)— the major effector lymphocytes of innate immunity. Maternal KIR genotype has been shown to affect the likelihood of severe pregnancy syndromes (Hiby et al 2004, 2008, 2010; Nakimuli et al 2015), and birth weight itself (Hiby et al 2014). All human populations—even those which have experienced extreme bottlenecks (Gendzekhadze et al 2006)—possess two KIR haplotypes with distinctly different gene contents. Why KIRs should have been segregated in this way in humans, and why KIR A and KIR B are always maintained in every human population, is an evolutionary phenomenon demanding explanation

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