Evolution of male pregnancy associated with remodeling of canonical vertebrate immunity in seahorses and pipefishes

Significance

Among vertebrates, pregnancy has evolved more than 150 times independently. A fundamental problem for pregnancy to evolve is inadvertent rejection of the embryo when being recognized as foreign tissue by the vertebrate’s adaptive immune system. We show that the unique evolution of male pregnancy in pipefishes and seahorses coincided with a genomic modification of one arm of the adaptive immune system. Our findings indicate a trade-off between immunological tolerance and embryo rejection to accompanying the emergence of male pregnancy. That syngnathids survive in an ocean of microbes despite their drastically modified immune defense suggests an unexpected immunological flexibility. Our results may improve the understanding of immune-deficiency diseases and call for a reassessment of vertebrate immunity.

Abstract

A fundamental problem for the evolution of pregnancy, the most specialized form of parental investment among vertebrates, is the rejection of the nonself-embryo. Mammals achieve immunological tolerance by down-regulating both major histocompatibility complex pathways (MHC I and II). Although pregnancy has evolved multiple times independently among vertebrates, knowledge of associated immune system adjustments is restricted to mammals. All of them (except monotremata) display full internal pregnancy, making evolutionary reconstructions within the class mammalia meaningless. Here, we study the seahorse and pipefish family (syngnathids) that have evolved male pregnancy across a gradient from external oviparity to internal gestation. We assess how immunological tolerance is achieved by reconstruction of the immune gene repertoire in a comprehensive sample of 12 seahorse and pipefish genomes along the “male pregnancy” gradient together with expression patterns of key immune and pregnancy genes in reproductive tissues. We found that the evolution of pregnancy coincided with a modification of the adaptive immune system. Divergent genomic rearrangements of the MHC II pathway among fully pregnant species were identified in both genera of the syngnathids: The pipefishes ( Syngnathus) displayed loss of several genes of the MHC II pathway while seahorses ( Hippocampus) featured a highly divergent invariant chain ( CD74). Our findings suggest that a trade-off between immunological tolerance and embryo rejection accompanied the evolution of unique male pregnancy. That pipefishes survive in an ocean of microbes without one arm of the adaptive immune defense suggests a high degree of immunological flexibility among vertebrates, which may advance our understanding of immune-deficiency diseases.