Biology subjects

Hatlen, A.

Publications and source records attributed to Hatlen, A..

3 recordsLinked to original sources

bioRxiv2019

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 compare it with predicted microRNA target sites to built 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 are available for downloading. We also describe a few illustrative examples.\n\nAvailability and implementationPoptargs is available at http://poptargs.essex.ac.uk\n\nContactamarco.bio@gmail.com

bioinformatics↗

bioRxiv2019

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 study variation at microRNA target sites in human populations and quantify 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, here we show that ignoring population diversity may leave out regulatory elements essential to understand disease and gene expression, particularly neglecting populations of African origin.

evolutionary biology↗

bioRxiv2018

Pervasive selection against microRNA target sites in human populations

MicroRNA target sites are often conserved during evolution and purifying selection to maintain such sites is expected. On the other hand, comparative analyses identified a paucity of microRNA target sites in co-expressed transcripts, and novel target sites can potentially be deleterious. We proposed that selection against novel target sites pervasive. The analysis of derived allele frequencies revealed that, when the derived allele is a target site, the proportion of non-target sites is higher than expected, particularly for highly expressed microRNAs. Thus, new alleles generating novel microRNA target sites can be deleterious and selected against. When we analysed ancestral target sites the derived (non-target) allele frequency does not show statistical support for microRNA target allele conservation. We investigated the joint effects of microRNA conservation and expression and found that selection against microRNA target sites depends mostly on the expression level of the microRNA. We identified microRNA target sites with relatively high levels of population differentiation. However, when we analyse separately target sites in which the target allele is ancestral to the population, the proportion of SNPs with high Fst significantly increases. These findings support population differentiation is more likely in target sites that are lost than in the gain of new target sites. Our results indicate that selection against novel microRNA target sites is prevalent and, although individual sites may have a weak selective pressure, the overall effect across untranslated regions is not negligible and should be accounted when studying the evolution of genomic sequences.

evolutionary biology↗