You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.

Title: Selection on the regulation of sympathetic nervous activity in humans and chimpanzees}
Article:
Abstract:
Adrenergic α2C receptor( ADRA2C) is an inhibitory modulator of the sympathetic nervous system. Knockout mice for this gene show physiological and behavioural alterations that are associated with the fight-or-flight response. There is evidence of positive selection on the regulation of this gene during chicken domestication. Here, we find that the neuronal expression of ADRA2C is lower in human and chimpanzee than in other primates. On the basis of three-dimensional chromatin structure, we identified a cis-regulatory region whose DNA sequences have been significantly accelerated in human and chimpanzee. Active histone modification marks this region in rhesus macaque but not in human and chimpanzee; instead, repressive marks are enriched in various human brain samples. This region contains two neuron-restrictive silencer factor( NRSF) binding motifs, each of which harbours a polymorphism. Our genotyping and analysis of population genome data indicate that at both polymorphic sites, the derived allele has reached fixation in humans and chimpanzees but not in bonobos, whereas only the ancestral allele is present among macaques. Our CRISPR/Cas9 genome editing and reporter assays show that both derived nucleotides repress ADRA2C, most likely by increasing NRSF binding. In addition, we detected signatures of recent positive selection for lower neuronal ADRA2C expression in humans. Our findings indicate that there has been selective pressure for enhanced sympathetic nervous activity in the evolution of humans and chimpanzees.
Introduction:
The sympathetic nervous system stimulates the fight-or-flight response of innervated target tissues by localized release of catecholamine neurotransmitters from the nerve terminals and by circulation of catecholamines released from the adrenal gland through the bloodstream. The adrenergic receptors are a class of G protein-coupled receptors that bind catecholamines, especially noradrenaline and adrenaline. α receptors have the subtypes α1( Gq coupled receptor) and α2( Gi coupled receptor). β receptors have the subtypes β1, β2 and β3. α2-adrenergic receptors are expressed not only on target tissues such as smooth muscles but also at sympathetic nerve terminals, where they function as inhibitory presynaptic autoreceptors that modulate the release of neurotransmitters. In particular, the α2C subtype( ADRA2C) modulates neurotransmission at lower levels of nerve activity in brain cortex[1]. Knockout mice for ADRA2C show more than a two-fold increase in circulating catecholamines[2] and behavioural alterations such as enhanced startle response, shortened attack latency, and diminished acoustic prepulse inhibition[3]. Multiple genes involved in the fight-or-flight response were identified as targets of selection during dog domestication[4]. In particular, one of the strongest selection signatures identified in the context of chicken domestication is located near ADRA2C[5]. Because there are no other known genes in the identified region, ADRA2C stands out as the most likely candidate. A follow-up study suggests that the target of selection may be noncoding regulatory regions that are distant from the gene body[6]. Genetic modifications in noncoding regulatory regions can be critical to human evolution. In their seminal work almost 40 years ago, King and Wilson[7] proposed a key role for regulatory modifications of noncoding DNA in shaping the evolution of our species. Indeed, the human genome contains noncoding DNA segments that are conserved in other species but show human-specific acceleration[8–12]. These accelerated elements were disproportionately found near genes involved in neuronal cell adhesion, indicating that noncoding changes in human evolution are associated with brain development and function[8]. Our incomplete knowledge of noncoding regions limits the functional interpretation of underlying DNA variants. Epigenomic signatures can mark the location of functional elements and provide systematic information on the spatiotemporal specificity of their regulatory activities[13–16]. Thus, the wealth of cell-type-specific human epigenomes provided by international consortia enable a systematic investigation of the regulatory mechanisms by which genetic variants affect phenotypes. For example, a majority of disease variants are located in DNase hypersensitive sites( DHSs) for the relevant cell types[13]. In this work, we sought to test whether noncoding regulatory regions of ADRA2C were under selection in humans by leveraging population genetics data and various epigenome data in neural cells or tissues. Humans and chimpanzees are the only primates that are known to frequently engage in warfare. Coalitionary attacks by chimpanzees on members of other groups resemble lethal intergroup raiding in humans. A recent study proposed that conspecific killing by chimpanzees is the result of adaptive strategies[17]. If intergroup aggression has been an adaptive or pervasive behaviour during the evolution of humans and chimpanzees, then the fight-or-flight response must have played a critical role in increasing fitness with constant exposure to lethal conflicts. Our study on the evolution of ADRA2C regulatory regions in humans will shed light on this hypothesis.
Discussion:
We examined a variety of transcriptomic, epigenomic, and population genomic data to identify selected regulatory variants that are responsible for human- and chimpanzee-specific repression of an inhibitory modulator of sympathetic nervous activity. It is unclear when the two variants arose in the population and reached near-fixation. One of them( DHS2. v2) might have arisen more recently and reached near-fixation only in humans and chimpanzees. The other variant( DHS2. v1) appears to be older considering that the bonobo and gorilla reference genomes carry the derived allele( Fig 3A). The derived allele frequency in the population of bonobos and gorillas remains to be investigated. However, derived alleles do not necessarily lead to gene repression. Other genetic factors that act in cis or trans must also be accounted for. For example, the same sequences at the two variants in human and chimpanzee appear to entail different repression mechanisms( H3K27me3 versus DNA methylation). In humans, we also identified two segregating variants that appear to reflect positive selection for lower neuronal ADRA2C expression. Similar population genetic and functional analyses for chimpanzees may shed light on how a different repression mechanism( H3K27me3 compared to DNA methylation) has evolved in humans. Regardless of the underlying mechanism, our results suggest that there has been selective pressure for enhanced sympathetic nervous activity during the evolution of humans as well as chimpanzees. Humans and chimpanzees are the only primates that are known to engage in regular lethal aggression among neighbouring groups, in contrast to their closest relatives, bonobos. A recent study proposed that conspecific killing by chimpanzees is more the result of adaptive strategies than the response to human disturbances[17]. This proposal could explain the evolutionary roots of warfare, which may be a pervasive feature throughout human history[41]. A recent study has suggested that there is a phylogenetic component in conspecific violence of humans[42]. It remains to be investigated whether intergroup aggression was a major factor that exerted this selective pressure.
Adrenergic α2C receptor ( ADRA2C ) is a regulator of the fight-or-flight response . It has been shown in mice that repression of this gene can result in relevant physiological and behavioral alterations . A strong selection signature in the genomes of domesticated chickens has been reported for this gene , suggesting that less aggression toward humans has been positively selected during chicken domestication . In this work , we analyze the genomes , transcriptomes , and epigenomes of a large number of humans and chimpanzees along with those of other primates to propose that repression of this gene has been positively selected in the evolution of humans and chimpanzees .