It is easy to get the numbers right and calculate neutrality index. It is easy to memorize "equals", "greater", "lesser", etc. At least on the exams, when certain level of simplicity is assumed. But instead of memorizing I'd prefer to understand. So far I struggle to get past the numbers. Could anyone, please, explain reasoning behind the them? Why certain values means the trait is advantageous or not? An easy to understand example would be helpful as well. Thank you.
(intraspecies non-synonymous polymorphisms)/(intraspecies synonymous polymorphisms) should equal the (mutation rate of non-synonymous mutations × number of non-synonymous sites)/(mutation rate of synonymous mutations × number of synonymous sites). Note that the mutation rate of synonymous mutations is just µ. Let F be the proportion of the synonymous mutations that are not deleterious so that the mutation rate of non-synonymous sites is Fµ. Let k be the ratio of synonymous sites over non-synonymous sites. Then the above fraction is equal to F/k. The same logic can be applied to find that the fraction of (interspecies non-syn polymorphisms)/(interspecies syn polymorphisms)=F/k, assuming the probability of fixation is roughly the same for synonymous and non-synonymous sites (neutral theory's assumption).
A helpful way to phrase it for me is that "If there's a disproportionate fraction of non-synonymous mutations between species relative to what exists within species, it is because non-synonymous mutations are being selected for in the one species but not in the other, thus there's positive selection."
By the way I'm not an expert in this so take the explanation with a grain of salt.