A Neanderthal Sodium Channel Increases Pain Sensitivity in Present-Day Humans.

The sodium channel Nav1.7 is crucial for impulse generation and conduction in peripheral pain pathways [1]. In Neanderthals, the Nav1.7 protein carried three amino acid substitutions (M932L, V991L, and D1908G) relative to modern humans. We expressed Nav1.7 proteins carrying all combinations of these substitutions and studied their electrophysiological effects. Whereas the single amino acid substitutions do not affect the function of the ion channel, the full Neanderthal variant carrying all three substitutions, as well as the combination of V991L with D1908G, shows reduced inactivation, suggesting that peripheral nerves were more sensitive to painful stimuli in Neanderthals than in modern humans. We show that, due to gene flow from Neanderthals, the three Neanderthal substitutions are found in ∼0.4% of present-day Britons, where they are associated with heightened pain sensitivity

The major genetic risk factor for severe COVID-19 is associated with protection against HIV

There are genetic risk factors that influence the outcome of COVID-19 [COVID-19 Host Genetics Initiative, Nature 600, 472–477 (2021)]. The major genetic risk factor for severe COIVD-19 resides on chromosome 3 and is inherited from Neandertals [H. Zeberg, S. Pääbo, Nature 587, 610–612 (2020)]. The risk-associated DNA segment modulates the expression of several chemokine receptors, among them CCR5, a coreceptor for HIV which is down-regulated in carriers of the COVID-19 risk haplotype. Here I show that carriers of the risk variant have an ∼27% lower risk of HIV infection

Tendencias actuales de la investigación genómica. Sus perspectivas en Nicaragua.

El contenido del artículo se enfoca en las tendencias y el impacto de las nuevas ciencias moleculares, cuyas revelaciones están transformando el mundo e incluso heredándonos una nueva cosmovisión. A continuación, se consideran las posibilidades de que un país pequeño como Nicaragua pueda contribuir en estas tendencias

An extended admixture pulse model reveals the limitations to human-Neandertal introgression dating

Neandertal DNA makes up 2–3% of the genomes of all non-African individuals. The patterns of Neandertal ancestry in modern humans have been used to estimate that this is the result of gene flow that occurred during the expansion of modern humans into Eurasia, but the precise dates of this event remain largely unknown. Here, we introduce an extended admixture pulse model that allows joint estimation of the timing and duration of gene flow. This model leads to simple expressions for both the admixture segment distribution and the decay curve of ancestry linkage disequilibrium, and we show that these two statistics are closely related. In simulations, we find that estimates of the mean time of admixture are largely robust to details in gene flow models, but that the duration of the gene flow can only be recovered if gene flow is very recent and the exact recombination map is known. These results imply that gene flow from Neandertals into modern humans could have happened over hundreds of generations. Ancient genomes from the time around the admixture event are thus likely required to resolve the question when, where, and for how long humans and Neandertals interacted

Ultrasonic vocalizations in mouse models for speech and socio-cognitive disorders: insights into the evolution of vocal communication

Comparative analyses used to reconstruct the evolution of traits associated with the human language faculty, including its socio-cognitive underpinnings, highlight the importance of evolutionary constraints limiting vocal learning in non-human primates. After a brief overview of this field of research and the neural basis of primate vocalizations, we review studies that have addressed the genetic basis of usage and structure of ultrasonic communication in mice, with a focus on the gene FOXP2 involved in specific language impairments and neuroligin genes (NL-3 and NL-4) involved in autism spectrum disorders. Knockout of FoxP2 leads to reduced vocal behavior and eventually premature death. Introducing the human variant of FoxP2 protein into mice, in contrast, results in shifts in frequency and modulation of pup ultrasonic vocalizations. Knockout of NL-3 and NL-4 in mice diminishes social behavior and vocalizations. Although such studies may provide insights into the molecular and neural basis of social and communicative behavior, the structure of mouse vocalizations is largely innate, limiting the suitability of the mouse model to study human speech, a learned mode of production. Although knockout or replacement of single genes has perceptible effects on behavior, these genes are part of larger networks whose functions remain poorly understood. In humans, for instance, deficiencies in NL-4 can lead to a broad spectrum of disorders, suggesting that further factors (experiential and/or genetic) contribute to the variation in clinical symptoms. The precise nature as well as the interaction of these factors is yet to be determined