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Contrasted patterns of variation and evolutionary convergence at the antiviral OAS1 gene in old world primates.

ABSTRACT: The oligoadenylate synthetase 1 (OAS1) enzyme acts as an innate sensor of viral infection and plays a major role in the defense against a wide diversity of viruses. Polymorphisms at OAS1 have been shown to correlate with differential susceptibility to several infections of great public health significance, including hepatitis C virus, SARS coronavirus, and West Nile virus. Population genetics analyses in hominoids have revealed interesting evolutionary patterns. In Central African chimpanzee, OAS1 has evolved under long-term balancing selection, resulting in the persistence of polymorphisms since the origin of hominoids, whereas human populations have acquired and retained OAS1 alleles from Neanderthal and Denisovan origin. We decided to further investigate the evolution of OAS1 in primates by characterizing intra-specific variation in four species commonly used as models in infectious disease research: the rhesus macaque, the cynomolgus macaque, the olive baboon, and the Guinea baboon. In baboons, OAS1 harbors a very low level of variation. In contrast, OAS1 in macaques exhibits a level of polymorphism far greater than the genomic average, which is consistent with the action of balancing selection. The region of the enzyme that directly interacts with viral RNA, the RNA-binding domain, contains a number of polymorphisms likely to affect the RNA-binding affinity of OAS1. This strongly suggests that pathogen-driven balancing selection acting on the RNA-binding domain of OAS1 is maintaining variation at this locus. Interestingly, we found that a number of polymorphisms involved in RNA-binding were shared between macaques and chimpanzees. This represents an unusual case of convergent polymorphism.

SUBMITTER: Fish I

PROVIDER: S-EPMC4809017 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The natural anti-Gal antibody is one of the multiple natural anti-carbohydrate antibodies produced in humans against a wide range of carbohydrate antigens on GI bacteria. The antibody is unique to humans, apes, and Old World monkeys, and it binds specifically to a mammalian carbohydrate antigen called the ?-gal epitope that is synthesized in nonprimate mammals, lemurs (prosimians) and New World monkeys by the glycosylation enzyme ?1,3GT. The ?1,3GT gene (GGTA1) appeared in mammals >100 million years ago, prior to the split between marsupial and placental mammals. This gene has been conserved in its active form, in all mammals, except for Old World monkeys, apes, and humans. Inactivation of the ?1,3GT gene in ancestral Old World primates occurred 20–30 million years ago and could have been associated with epidemics of enveloped viruses in the Eurasia-Africa continent. It is suggested that prior to such epidemics, few ancestral Old World primates acquired deletion point mutations that inactivated the ?1,3GT gene and eliminated ?-gal epitopes. This resulted in loss of immune tolerance to the ?-gal epitope and thus, in production of the anti-Gal antibody against antigens on bacteria colonizing the GI tract. This accidental inactivation of the ?1,3GT gene in very small populations is analogous to the highly rare blood type “Bombay” individuals who do not synthesize blood group H (O antigen) because of inactivation of the ?1,2-fucosyltransferase gene. The loss of immune tolerance to blood group H antigen has resulted in production of natural anti-blood group H antibodies in the blood group Bombay individuals. It is suggested that anti-Gal protected against infections by enveloped viruses presenting ?-gal epitopes, which were lethal to the parental primate populations that conserved active ?1,3GT and thus, synthesized ?-gal epitopes. Alternative causes for the elimination of Old World primates synthesizing ?-gal epitopes could be bacteria or protozoa parasites presenting ?-gal or ?-gal-like epitopes, and bacterial toxins, or detrimental viruses that used ?-gal epitopes in these primates as “docking receptors.” Ultimately, any of these proposed selective processes could result in extinction of Old World primates synthesizing ?-gal epitopes on their cells. These ancestral primates were replaced by offspring populations lacking ?-gal epitopes and producing the anti-Gal antibody, which continues to be produced by Old World monkeys, apes, and humans. New World monkeys and lemurs were protected from pathogens of the Old World by oceanic barriers, thus they continue to synthesize ?-gal epitopes and lack the ability to produce the anti-Gal antibody. This scenario of few individuals in a large population having a mutation(s) that inactivates a glycosyltransferase gene thus, resulting in production of evolutionary advantageous natural antibodies against the eliminated carbohydrate antigen, may reflect one of the mechanisms inducing changes in the carbohydrate profile of various mammalian populations.

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Contrasted patterns of variation and evolutionary convergence at the antiviral OAS1 gene in old world primates.

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