PMID:21987817

Citation	Ghaderi, D, Springer, SA, Ma, F, Cohen, M, Secrest, P, Taylor, RE, Varki, A and Gagneux, P (2011) Sexual selection by female immunity against paternal antigens can fix loss of function alleles. Proc. Natl. Acad. Sci. U.S.A. 108:17743-8
Abstract	Humans lack the common mammalian cell surface molecule N-glycolylneuraminic acid (Neu5Gc) due to a CMAH gene inactivation, which occurred approximately three million years ago. Modern humans produce antibodies specific for Neu5Gc. We hypothesized that anti-Neu5Gc antibodies could enter the female reproductive tract and target Neu5Gc-positive sperm or fetal tissues, reducing reproductive compatibility. Indeed, female mice with a human-like Cmah(-/-) mutation and immunized to express anti-Neu5Gc antibodies show lower fertility with Neu5Gc-positive males, due to prezygotic incompatibilities. Human anti-Neu5Gc antibodies are also capable of targeting paternally derived antigens and mediate cytotoxicity against Neu5Gc-bearing chimpanzee sperm in vitro. Models of populations polymorphic for such antigens show that reproductive incompatibility by female immunity can drive loss-of-function alleles to fixation from moderate initial frequencies. Initially, the loss of a cell-surface antigen can occur due to drift in isolated populations or when natural selection favors the loss of a receptor exploited by pathogens, subsequently the same loss-of-function allele can come under sexual selection because it avoids being targeted by the female immune system. Thus, we provide evidence of a link between sexual selection and immune function: Antigenicity in females can select against foreign paternal antigens on sperm and rapidly fix loss-of-function alleles. Similar circumstances existed when the CMAH null allele was polymorphic in ancestral hominins, just before the divergence of Homo from australopithecines.
Links	PubMed PMC3203784 Online version:10.1073/pnas.1102302108
Keywords	Animals; Antibodies/immunology; Antigens/immunology; Female; Gene Frequency; Genetics, Population; Humans; Male; Mating Preference, Animal/physiology; Mice; Mice, Knockout; Mixed Function Oxygenases/genetics; Mixed Function Oxygenases/metabolism; Neuraminic Acids/immunology; Pan troglodytes/immunology; Pan troglodytes/metabolism; Selection, Genetic; Sialic Acids/metabolism; Spermatozoa/immunology; Spermatozoa/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:CMAH	enables	GO:0030338: CMP-N-acetylneuraminate monooxygenase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
MOUSE:CMAH		GO:0030338: CMP-N-acetylneuraminate monooxygenase activity	ECO:0000314:		F		Figure 2A	complete CACAO 2454

References

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