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Consider this scenario where a mutation in the immune system would cause a mutant offspring, and perhaps even speciation. If the immune system mutates or changes due to environmental factors, it could alter the immune challenge that it presents to the gametes (specifically all those sperm), thereby causing a “natural selection” to occur within the parent’s body — most likely the male’s body with all its sperm. This may allow some different gametes to survive, increasing their chance to fertilize an egg, and going on to produce a mutant offspring, perhaps a new species. If environmental factors affect the immune system and/or the gametes in a population of individuals, then enough mutant offspring of the same new species may allow for enough genetic diversity so as to successfully give rise to a robust, new species.
Mutation to the immune system might also provide a new species with “self knowledge” that it is a new species. Such mutations may allow the individual’s central nervous system to recognize others of its “kind” as kin — ie, as those with whom it should socialize and as potential reproductive mates. For example, the first humans would have recognized other new humans as potential mates, and not the primates from which they came. Otherwise, given the number of new species members to old species members, there would be a lot of fruitless inter-species miscegenation — not the kind of behavior that fosters successful, new species.