@article{TEXTUAL,
      recid = {5912},
      author = {Findley, Anthony S. and Zhang, Xinjun and Boye, Carly and  Lin, Yen Lung and Kalita, Cynthia A. and Barreiro, Luis and  Lohmueller, Kirk E. and Pique-Regi, Roger and Luca,  Francesca},
      title = {A signature of Neanderthal introgression on molecular  mechanisms of environmental responses},
      journal = {PLOS Genetics},
      address = {2021-09-27},
      number = {TEXTUAL},
      abstract = {<p>Ancient human migrations led to the settlement of  population groups in varied environmental contexts  worldwide. The extent to which adaptation to local  environments has shaped human genetic diversity is a  longstanding question in human evolution. Recent studies  have suggested that introgression of archaic alleles in the  genome of modern humans may have contributed to adaptation  to environmental pressures such as pathogen exposure.  Functional genomic studies have demonstrated that variation  in gene expression across individuals and in response to  environmental perturbations is a main mechanism underlying  complex trait variation. We considered gene expression  response to in vitro treatments as a molecular phenotype to  identify genes and regulatory variants that may have played  an important role in adaptations to local environments. We  investigated if Neanderthal introgression in the human  genome may contribute to the transcriptional response to  environmental perturbations. To this end we used eQTLs for  genes differentially expressed in a panel of 52 cellular  environments, resulting from 5 cell types and 26  treatments, including hormones, vitamins, drugs, and  environmental contaminants. We found that SNPs with  introgressed Neanderthal alleles (N-SNPs) disrupt binding  of transcription factors important for environmental  responses, including ionizing radiation and hypoxia, and  for glucose metabolism. We identified an enrichment for  N-SNPs among eQTLs for genes differentially expressed in  response to 8 treatments, including glucocorticoids,  caffeine, and vitamin D. Using Massively Parallel Reporter  Assays (MPRA) data, we validated the regulatory function of  21 introgressed Neanderthal variants in the human genome,  corresponding to 8 eQTLs regulating 15 genes that respond  to environmental perturbations. These findings expand the  set of environments where archaic introgression may have  contributed to adaptations to local environments in modern  humans and provide experimental validation for the  regulatory function of introgressed variants.</p>},
      url = {http://knowledge.uchicago.edu/record/5912},
}