Preserving immune diversity through ancient inheritance and admixture

• Immune functions are strongly targeted by natural selection in the human genome.
• Long-term balancing selection can preserve immune diversity across species.
• Advantageous immune alleles can be acquired by admixture with archaic humans.
• High HLA and KIR diversity has been preserved in populations worldwide.
• Selection studies highlight immune functions that are essential for host survival.

The progress of genomic technologies is allowing researchers to scan the genomes of different species for the occurrence of natural selection at an unprecedented level of resolution. These studies show that genes involved in immune processes are preferential targets of different forms of selection, some of which act to preserve immune diversity over time. Recent work in humans shows that this can be achieved either by inheriting advantageous immune variation from distant ancestral species, through long-term balancing selection, or by acquiring novel selected alleles through admixture with extinct hominins such as Neanderthals or Denisovans. These studies collectively increase our knowledge of immune genes for which maintaining the functional diversity has conferred a strong selective advantage for host survival.