BackgroundNon-celiac wheat sensitivity is an emerging wheat-related syndrome showing peak prevalence in Western populations. Recent studies hypothesize that new gliadin alleles introduced in the human diet by replacement of ancient wheat with modern varieties can prompt immune responses mediated by the CXCR3-chemokine axis potentially underlying such pathogenic inflammation. This cultural shift may also explain disease epidemiology, having turned European-specific adaptive alleles previously targeted by natural selection into disadvantageous ones.MethodsTo explore this evolutionary scenario, we performed ultra-deep sequencing of genes pivotal in the CXCR3-inflammatory pathway on individuals diagnosed for non-celiac wheat sensitivity and we applied anthropological evolutionary genetics methods to sequence data from worldwide populations to investigate the genetic legacy of natural selection on these loci.ResultsOur results indicate that balancing selection has maintained two divergent CXCL10/CXCL11 haplotypes in Europeans, one responsible for boosting inflammatory reactions and another for encoding moderate chemokine expression.ConclusionsThis led to considerably higher occurrence of the former haplotype in Western people than in Africans and East Asians, suggesting that they might be more prone to side effects related to the consumption of modern wheat varieties. Accordingly, this study contributed to shed new light on some of the mechanisms potentially involved in the disease etiology and on the evolutionary bases of its present-day epidemiological patterns. Moreover, overrepresentation of disease homozygotes for the dis-adaptive haplotype plausibly accounts for their even more enhanced CXCR3-axis expression and for their further increase in disease risk, representing a promising finding to be validated by larger follow-up studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12263-016-0532-4) contains supplementary material, which is available to authorized users.

Investigation of human mitochondrial DNA variation patterns and phylogeny has been extensively used in Anthropological and Population Genetics studies and sequencing the whole mitochondrial genome is progressively becoming the gold standard. Among the currently available massive parallel sequencing technologies, Ion Torrent™ semiconductor sequencing represents a promising approach for such studies. Nevertheless, an experimental protocol conceived to enable the achievement of both as high as possible yield and of the most homogeneous sequence coverage through the whole mitochondrial genome is still not available. The present work was thus aimed at improving the overall performance of whole mitochondrial genomes Ion Torrent™ sequencing, with special focus on the capability to obtain robust coverage and highly reliable variants calling. For this purpose, a series of cost-effective modifications in standard laboratory workflows was fine-tuned to optimize them for medium- and large-scale population studies. A total of 54 human samples were thus subjected to sequencing of the whole mitochondrial genome with the Ion Personal Genome Machine™ System in four distinct experiments and using Ion 314 chips. Seven of the selected samples were also characterized by means of conventional Sanger sequencing for the sake of comparison. Obtained results demonstrated that the implemented optimizations had definitely improved sequencing outputs in terms of both variants calling efficiency and coverage uniformity, enabling to setup an effective and accurate protocol for whole mitochondrial genome sequencing and a considerable reduction in experimental time consumption and sequencing costs.