BACKROUND: Human sequence acceleration has been reported to have revamped the status of present-day humans over the course of evolution and has immensely contributed to their efficient adaptation to do highly complicated assessments. Human accelerated DNA fragments are those bits of the genome that have experienced frequent sequential changes after the human-chimp split despite being strongly conserved among mammals. Previous studies have indicated that many such accelerated genomic segments happen to harbor cis-regulatory elements, among which enhancers take up the most portion. Enhancers make up the distal category of cis-regulatory elements that could reside many kilobases away from their target genes and contribute in initiation of cell specific gene expression.Recent findings have also brought to our notice that coding region mutations shared with archaic humans were followed by substitutions in regulatory elements that were Homo sapien-unique and hence attributed to anatomically profound modern human traits. Following this deduction, we opted for brain that is the most profoundly adapted organ in the present-day human anatomy, characterizing them as the most cognitively advanced species. We focussed on acceleration of enhancers that express solely in the brain region. With respect to that, craniofacial development due to an increased brain size during the course of primate evolution has also garnered immense attention over the past many years. The relevance of this increase in brain size and its direct impact in formulating the facial mechanics of humans, both archaic and modern, has left many questions unanswered. Climate is one leading factor that imposed evolutionary constraints over the human facial dynamics. While observing such wide variety of facial forms in the present-day human population, it becomes evidently intriguing to probe into genetic factors that might have given in to the forces of natural selection. With the advent of genome wide association studies, we now have a decent collection of single nucleotide polymorphisms that are associated with various facial features. We took nasal morphology as our case study for being nature‟s profound conditioning system in the human body. By keeping out-of-Africa ancient migrations in mind, we observe a drastic climatic shift from an extremely hot-humid environment of Africa to relatively temperate regions of Asia and extremely cold Europe. Following the pattern of nasal variation on these lines, the aim of our study ensures a link between nasal adaptations to climatic change as wide-bulbous noses are significant features of hothumid climate and narrower-taller noses represent a much colder climate. RESULTS: This study relied on empirically confirmed brain exclusive enhancers to avoid any misjudgments about their regulatory status and categorized among them a subset of enhancers with an exceptionally accelerated rate of lineage specific divergence in humans. Among these accelerated enhancers, we found an assorted set of 13 distinct transcription factor binding sites were located that possessed unique existence in humans. 3/13 such sites belonging to transcription factors SOX2, RUNX1/3 and FOS/JUND possessed single nucleotide variants that made them unique to H. sapiensupon comparisons with Neanderthal and Denisovan orthologous sequences. These variants modifying the binding sites in modern human lineage were further substantiated as single nucleotide polymorphisms via exploiting 1000 Genomes Project Phase III data. Long range haplotype (LRH) based tests laid out evidence of positive selection to be governing in African population on two of the modern human motif modifying alleles with strongest results for SOX2 binding site. For nasal phenotype assessment on the basis of genetic variation, we gathered a set of SNPs from six GWAS studies till date, each associated with a particular nasal feature and applied tests so as to determine the pattern of contrasting selection over alleles in regions of climatic opposites. We incorporated 2504 individuals‟ data from 1000 Genomes Project Phase III. We observed 9 such SNPs that made strong cases of positive selection on either of their allelic variants (derived or ancestral). Among them, we also observed SNPs that conspicuously showed varying patterns of selection on either of the alleles in Africa (hot-humid climate) in comparison with four nonAfrican populations (temperate or colder climates), hence, highlighting a climatically driven, contrasting patterns of divergence of alleles that favored a particular nasal phenotype. CONCLUSION: Our study concludes that sequence divergence in the regulatory repertoire of modern humans underlie their vast phenotypic leverage over other species, brain being the crown of all such adaptations. We also concluded that Homo sapien-specific binding site variants in these enhancers are prone to accelerated divergence across the current-day human population and could be involving a functional advantage. We also gauged in this study that nasal type variation in different regions of the world are climatically driven. Our data also highlights the uniqueness of these substitutions, as majority of the human specific substitutions are not shared with Neanderthals and Denisovans. Also, the occurrence of these SNPs in non-coding part of the genome also points towards a new aspect in which cisregulatory evolution could be playing a significant role in devising the nasal morphological mechanics of the present-day human population.