Mutation accumulation theory |
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Figure 5 : Accumulations of
deleterious mutations can occur in the selection shadow because after
reproduction, natural selection is weak [see figure 3]
(Kirkwood and
Austad, 2000). |
Description and Predictions Peter Medawar suggested that
ageing is a by-product of accumulation of deleterious mutations over time.
Due to stochastic risk of accident, or illness leading to death there is a
decreasing probability of reaching more advanced ages. Deleterious germ line
mutations are selected against early in life when chance of survival and
reproduction is high but are hidden from natural selection (the shadow area
in figure 5) at old age (Kirkwood and
Austad, 2000). Mutation accumulation (MA)
emphasises the concept that ageing is a stochastic by-product of a
mutation-selection balance for early age fitness at the cost of longevity.
None of the genes involved have been shown to have an effect only on ageing
which agrees with evolution theory statements that genes most likely do not
exist for ageing alone (Kirkwood, 2002).
It predicts that organisms maintain more deleterious alleles with small
effects as they age. These late-acting mutations are said to increase
mortality with age (Gavrilov and Gavrilova, 2002)
Mutation accumulation predicts that genetic diseases should increase
in frequency with age and that there could be large heterogeneity in
deleterious genes between different individuals throughout the entire genome
(Kirkwood, 2002).
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Experimental evidence The theory of mutation
accumulation has been tested in experimental conditions with varying rates of
success. In one study on Drosophila,
a statistically significant increase was observed in genetic variation and
inbreeding effect with age which are both predictions of MA theory (Hughes et al.,
2002). It is theorized that age-related increases in
dominant and homozygous genetic variance as well as inbreeding depression
will occur only under mutation accumulation. Using transgenic flies with
balancer chromosome techniques to construct lines with identical homozygous
or heterozygous genotypes, Hughes et al.,
found that both lines experienced reduction in reproduction success.
Inbreeding depression was observed to increase with age as did dominance and
homozygous line variance. Unfortunately, later research has found that MA predictions are not met in similar experiments. One main component of MA theory is that the accumulation of mutations after reproduction would be stochastic and therefore different between different individuals of the same species. This genetic variable can be used in other studies looking at mutation accumulation effect. It is likely that accumulation does occur but most support has been given to the importance of pleiotropy theory (Hughes and Reynolds, 2005). |
Figure 6: Male and female
drosophila. Fruit-flies are a model organism for many studies concerned with
ageing. |
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