PopTargs: a database for studying population evolutionary genetics of human microRNA target sites.

There is an increasing interest in the study of polymorphic variants at gene regulatory motifs, including microRNA target sites. Understanding the effects of selective forces at specific microRNA target sites, together with other factors like expression levels or evolutionary conservation, requires the joint study of multiple datasets. We have compiled information from multiple sources and compared it with predicted microRNA target sites to build a comprehensive database for the study of microRNA targets in human populations. PopTargs is a web-based tool that allows the easy extraction of multiple datasets and the joint analyses of them, including allele frequencies, ancestral status, population differentiation statistics and site conservation. The user can also compare the allele frequency spectrum between two groups of target sites and conveniently produce plots. The database can be easily expanded as new data becomes available and the raw database as well as code for creating new custom-made databases is available for downloading. We also describe a few illustrative examples.

The Impact of Population Variation in the Analysis of microRNA Target Sites.

The impact of population variation in the analysis of regulatory interactions is an underdeveloped area. MicroRNA target recognition occurs via pairwise complementarity. Consequently, a number of computational prediction tools have been developed to identify potential target sites that can be further validated experimentally. However, as microRNA target predictions are done mostly considering a reference genome sequence, target sites showing variation among populations are neglected. Here, we studied the variation at microRNA target sites in human populations and quantified their impact in microRNA target prediction. We found that African populations carry a significant number of potential microRNA target sites that are not detectable in the current human reference genome sequence. Some of these targets are conserved in primates and only lost in Out-of-Africa populations. Indeed, we identified experimentally validated microRNA/transcript interactions that are not detected in standard microRNA target prediction programs, yet they have segregating target alleles abundant in non-European populations. In conclusion, we show that ignoring population diversity may leave out regulatory elements essential to understand disease and gene expression, particularly neglecting populations of African origin.