@article {12995, title = {Sexual selection by female immunity against paternal antigens can fix loss of function alleles}, journal = {Proc Natl Acad Sci U S A}, volume = {108}, number = {43}, year = {2011}, note = {

Proc Natl Acad Sci U S A.\ 2011 Oct 25;108(43):17743-8. doi: 10.1073/pnas.1102302108. Epub 2011 Oct 10.\ 

}, month = {Oct 25}, pages = {17743-8}, type = {Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}t}, edition = {2011/10/12}, 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.

}, keywords = {Animal/*physiology, Animals, Antibodies/*immunology, Antigens/immunology, Female, Gene Frequency, Genetics, Humans, Knockout, Male, Mating Preference, Mice, Mixed Function Oxygenases/*genetics/metabolism, Neuraminic Acids/*immunology, Pa, Population}, isbn = {1091-6490 (Electronic)00}, url = {http://www.ncbi.nlm.nih.gov/pubmed/21987817}, author = {Ghaderi, D. and Springer, S. A. and Ma, F. and Cohen, M. and Secrest, P. and Taylor, R. E. and Ajit Varki and Gagneux, P.} }