I have a problem with understanding how ‘neutral’ or synonymous mutations in mitogenomes can be treated in coalescent analyses that require selective neutrality, such as BSP, eBSP or mismatch analyses. Imagine that a synonymous mutation occurs at one mt nucleotide site and then another favourable mutation occurs anywhere else in the mitogenome. If there is no recombination between mitogenomes, wouldn’t this new synonymous mutation experience the same selective response as the favourable mutation? I have trouble getting my head around this question, but wouldn’t it mean that that there are no neutral mutations in mitochondria unless there is no selection happening anywhere in the mitogenome?
Synonymous mutations are not necessarily selectively neutral - for example the mutation may impact on secondary/tertiary structure folding, some ncRNA binding affinity, or translational efficiency. A synonymous mutation may actually negate or enhance the assumed selective advantage of a 'favorable' mutation elsewhere in the mtDNA. Furthermore you need to consider the impact that heteroplasmy may be having on your analysis.
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