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Background  Coevolution has been used to identify and predict interactions and functional relationships between proteins of many different organisms including humans. Current efforts in annotating the human genome increasingly show that non-coding DNA sequence has important functional and regulatory interactions. Furthermore, regulatory elements do not necessarily reside in close proximity of the coding region for their target genes.    Results  We characterize coevolution as it appears in locus-gene interactions in the human genome, focusing on expression Quantitative Trait - Locus (eQTL) interactions. Our results show that in these interactions the conservation status of the loci is predictive of the conservation status of their target genes. Furthermore, comparing the phylogenetic histories of intra-chromosomal pairs of loci and transcription start sites, we find that pairs that appear coevolved are enriched for cis-eQTL interactions. Exploring this property we found that coevolution might be useful in prioritizing association tests in cis-eQTL detection.    Conclusions  The relationship between the conservation status of pairs of loci and protein coding transcription start sites reveal correlations with regulatory interactions. Pairs that appear coevolved are enriched for intra-chromosomal regulatory interactions, thus our results suggest that measures of coevolution can be useful for prediction and detection of new interactions. Measures of coevolution are genome-wide and could potentially be used to prioritize the detection of distant or inter-chromosomal interactions such as trans-eQTL interactions in the human genome.    Electronic supplementary material  The online version of this article (10.1186/s13040-019-0195-y) contains supplementary material, which is available to authorized users.

Characterizing human genomic coevolution in locus-gene regulatory interactions