Searching for signatures of cold adaptation in Neandertal and Denisovan genomes, hints from the brown adipose tissue genes

Western and eastern Eurasian populations of Neandertal and Denisovan sister clades of archaic hominins have basically experienced temperatures significantly lower than the present ones, also occupying geographical regions involved in the Pleni-Wurm for a time interval long enough to adapt to this cold environment. In fact, paleoanthropological evidences prove that Neandertal body proportions are in accordance with a minimization of the ratio between body surface area and volume in order to avoid heat loss, as regards both their voluminous thorax and their relatively short length of limbs that is found to be significantly lower even with respect to that of modern humans belonging to cold adapted populations. Moreover, Neandertal supposed massive muscular apparatus and hunter-gatherer subsistence strategies suggest that their life-style was similar to H. sapiens populations living in circumpolar regions, being mainly characterized by a diet rich in fat and proteins, thus able to satisfy a calorie needs ranging from 4,000 to 7,000 kcal/day. All these features, together with a high basal metabolic rate, may have favored the isolation from cold and the thermogenic functions in these archaic hominins. Furthermore, it can be hypothesized that the advent of new subsistence strategies and the increase of environmental temperature during recent human evolution may have been too fast for completely retuning the basic processes of thermogenesis and thermoregulation in our species, so that even slight differences in their regulation between H. sapiens and Neandertals/Denisovans could be the key between our way to store and spend energy and that of our ancestors. Thermogenesis and thermoregulation consist in complex functional patterns centered on the dissipation of heat in the mitochondria by uncoupling oxidation and ATP synthesis and are mainly provided by adipocytes belonging to the Brown Adipose Tissue (BAT), which contain a great amount of mitochondria and which differentiate from precursors of muscle cells. In this exploratory work, we investigated the genetic similarities/differences between 27 Neandertal, Denisovan and modern human genes involved in BAT metabolism, storage and neogenesis, or being found to be associated with fat accumulation and body mass index according to GWAS studies. Neandertal and Denisovan sequence data were thus retrieved from public databases, together with those from 1,122 modern humans belonging to 14 populations sequenced in the pilot phase of the “1000Genomes” project, and exploited to identify new Neandertal/Denisova-specific variants, as well as to explore whether the examined archaic samples exhibit genetic similarities, in the genomic regions under investigation, to individuals from modern human populations exposed to cold environments.