Neutral markers provide insight into levels of variation but do not take into account selective environmental pressures of a species and therefore do not provide information in an evolutionary context as would the use of non-neutral markers.
Is there any key significance or insight in using a neutral and non-neutral marker in conjunction for a population genetic study?
Most of the models in population genetics are based on the neutrality hypothesis. Many of the equations were derived by coalescent simulation, which is also based on neutrality. Therefore, it is useful to include in your analysis some loci which are likely to be neutral. Neutral loci are also useful as a reference (control) when studying genes which are under selection. For example, the HKA neutrality test is based on comparing neutral and non-neutral loci. For the same reason, analysing neutral loci is also useful for dating a variation. This become far more complicated with loci under selection.
Salem, Asif
It all depends on your goal of study. If you want to perform a phylogenetic comparison study between populations of the same species, the choice of neutral markers is a priority. By cons, if you want to master stock of the differences between populations it better choose your markers linked to genes that are responsible for differences between populations.
Eran & Semir , Thank you for your response.
I've used neutral and non-neutral markers and was just attempting to bounce some ideas to see if there was some new level of insight in combing both types of markers. What are the pitfalls of using coalescent simulations of population expansion tests on non-neutral markers.
Salem, Asif
one using markers that are not neutral you several situations
you will study the impact of the operating system on the relationship between the population (if the markers are linked to characters of economic interest, for example)
you can identify the gene that controls the character if the comparison is between two very close people.
But it is sure you will not have a real idea about the phylogenetic relationships.
To begin with, it must be said that you may have some a priori idea about whether a given marker is neutral or has been under selection, however, you cannot know for sure. A coding locus with alleles responsible for different phenotypes could be neutral (phenotypes have or had the same fitness). A microsatellite or other "junk" DNA could be linked to a locus under selection and hitch-hike or have an unknown function and be responsible for changes in fitness. So beware of your assumptions about using a priori neutral and non-neutral markers.
Current widely accepted approach is to consider that the vast majority of the genome behaves neutral and only a handful of loci have been under recent selection. Therefore, we can perform demographic inference from lots of (randomly selected along the genome) markers. If some markers under selection are included, it is assumed that their signal is "crushed" compared to the main neutral signal carried by the overwhelming majority of neutral markers. See however Ewing & Jensen (2016, doi:10.1111/mec.13390).
Once the demographic history of the populations under study has been inferred one can try to detect loci that present diversity pattern incompatible to that history. These can be assumed to have been under selection.
If you want to distinguish between neutral and non-neutral markers, it is important to look for deviating behavior. Extremely high or low differentiation among populations and/or correlations with environmental gradients can be indicative of selection. If you want to be sure, remove all markers behaving like this to prevent violating neutral theory.
On the other hand, it may be very interesting to compare diversity and differentiation patterns between putative neutral and potentially non-neutral markers. After all, it is rather the non-neutral markers that create adaptive potential.
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