Mutation accumulation and antagonistic pleiotropy have historically represented the two big camps of ageing theorists, and the theories have traditionally been regarded as being in opposition to each other. I’ve never really understood why, though: the basic insight required to understand both theories is the same, and conditions that gave rise to ageing via mutation accumulation could easily also give rise to additional ageing via antagonistic pleiotropy[6]. Importantly, both theories give the same kinds of answers to the other two key questions of ageing I discussed last time: why do lifespans differ between species, and why do some animals escape ageing altogether?
I’ve also seen this in some literature, but a Google Scholar search for “mutation accumulation antagonistic pleiotropy” is popping up papers framing them as complementary. Mostly, I see three angles: simply accepting that both are well-supported, asking which is most important, or challenging the evidence for one or the other. But I don’t see papers in this convenience sample framing them as mutually exclusive.
Antagonistic pleiotropy and mutation accumulation influence human senescence and disease
As senescence is a highly complex phenomenon, ideas about it [mutation accumulation, antagonistic pleiotropy, disposable soma] are better understood as complementing than as excluding each other.
Antagonistic pleiotropy and mutation accumulation contribute to age-related decline in stress response
The evolution of age-related changes associated with senescence is likely influenced by mutation accumulation (MA) and antagonistic pleiotropy (AP).
Antagonistic pleiotropy, mutation accumulation, and human genetic disease
This one from 1993, and points out that (at least at that time):
no locus or allele has been identified in a wild population with the features predicted by the pleiotropic theory… Inability to find an early life selective benefit associated with these disease-causing alleles would favor the major alternative genetic explanation for aging, the mutation accumulation theory.
Retesting the influences of mutation accumulation and antagonistic pleiotropy on human senescence and disease
Note that this paper rejects the finding of the first paper I linked above, based on a reanalysis (“their findings seem idiosyncratic and their evidence for the MA hypothesis is not robust.”).
The MA hypothesis states that natural selection is ineffective in purging mutations that cause senescence as these mutations have little fitness consequence due to the absence of phenotypic effects until after the reproductive age. The related AP hypothesis asserts that these mutations may even be selectively favoured because they promote growth or reproduction owing to their pleiotropic effects.
Is antagonistic pleiotropy ubiquitous in aging biology? This paper asks which model, MA or AP, is most important, rather than viewing them as mutually exclusive.
But which theory of aging, mutation accumulation or antagonistic pleiotropy, is more pervasive across species?
Antagonistic Pleiotropy in Human Disease
Almost a century later, these aging theories, including antagonistic pleiotropy and mutation accumulation, have been experimentally validated in animals.
I’ve also seen this in some literature, but a Google Scholar search for “mutation accumulation antagonistic pleiotropy” is popping up papers framing them as complementary. Mostly, I see three angles: simply accepting that both are well-supported, asking which is most important, or challenging the evidence for one or the other. But I don’t see papers in this convenience sample framing them as mutually exclusive.
Antagonistic pleiotropy and mutation accumulation influence human senescence and disease
Antagonistic pleiotropy and mutation accumulation contribute to age-related decline in stress response
Antagonistic pleiotropy, mutation accumulation, and human genetic disease
This one from 1993, and points out that (at least at that time):
Retesting the influences of mutation accumulation and antagonistic pleiotropy on human senescence and disease
Note that this paper rejects the finding of the first paper I linked above, based on a reanalysis (“their findings seem idiosyncratic and their evidence for the MA hypothesis is not robust.”).
Is antagonistic pleiotropy ubiquitous in aging biology?
This paper asks which model, MA or AP, is most important, rather than viewing them as mutually exclusive.
Antagonistic Pleiotropy in Human Disease