ena-STUDY-UNIVERSITY OF BERN-02-10-2020-13:09:07:291-50
A GLYCAN-BASED TRADE-OFF WITH IMPLICATIONS TO HOMINIDAE EVOLUTION
Most mammals carry a functional N-acetyllactosaminide alpha-1,3-galactosyltransferase 1 (GGTA1) gene, which encodes the enzyme synthetizing Gala1-3Galß1-4Glc (aGal). In contrast, anthropoid monkeys, including humans, carry loss-of-function mutations in GGTA1 and lack aGal (1, 2). Natural selection and fixation of these mutations allowed for the emergence of aGal-specific immunity, enhancing resistance to pathogens expressing aGal (3-5). Here we demonstrate that loss of Ggta1 function in mice enhances resistance to bacterial sepsis, irrespectively of aGal-specific immunity. This is owed instead to enhanced IgG bactericidal activity, driven by improved IgG binding to the Fc gamma receptor IV (Fc?RIV). As a trade-off, Ggta1 loss of function causes earlier onset of reproductive senescence, a major fitness cost at play during the early stages of hominidae evolution.
Most mammals carry a functional N-acetyllactosaminide alpha-1,3-galactosyltransferase 1 (GGTA1) gene, which encodes the enzyme synthetizing Gala1-3Galß1-4Glc (aGal). In contrast, anthropoid monkeys, including humans, carry loss-of-function mutations in GGTA1 and lack aGal (1, 2). Natural selection and fixation of these mutations allowed for the emergence of aGal-specific immunity, enhancing resistance to pathogens expressing aGal (3-5). Here we demonstrate that loss of Ggta1 function in mice enhances resistance to bacterial sepsis, irrespectively of aGal-specific immunity. This is owed instead to enhanced IgG bactericidal activity, driven by improved IgG binding to the Fc gamma receptor IV (Fc?RIV). As a trade-off, Ggta1 loss of function causes earlier onset of reproductive senescence, a major fitness cost at play during the early stages of hominidae evolution.