НAR: история, функции, роль в эволюции и патогенезе заболеваний человека

It is assumed that changes in gene regulation mechanisms play a major role in human evolution rather than proteincoding sequence changes. Recent studies have identified human accelerated regions (HARs) - a special class of genomic elements. These non-coding DNA regions are highly conserved in mammals but show an increased number of substitutions in the human lineage. Since their discovery, the actual role of HARs in human evolution has remained obscure as they are almost exclusively represented by unannotated non-coding sequences. HARs are enriched in transcription factor binding motifs and active histone modifications. Recent studies used functional genomics, computational approaches, and genetic analysis to show that many HARs are involved in the developmental genes regulation and the evolution of the human brain. There is also a body of evidence linking polymorphisms in HARs with various neuropathologies such as autism spectrum disorders, schizophrenia, and Huntington's disease. Functional assays such as high-throughput reporter analysis and CRIS PR-based screenings significantly increased the number of human-specific regulatory elements characterized. Further exploration of HARs and other evolutionarily dynamic regions in the genome may elucidate some of the complex evolutionary changes that underlie the unique cytoarchitecture and cognitive abilities of the human brain. In this review, we consider different approaches used to identify HARs, their role in gene regulation, their contribution to the evolution of the human brain, and highlight some of the pathological effects of mutations in HARs.