Publications in Current Biology

Neanderthals had a robust build and distinctive skeletal features. The hypothalamic-pituitary-somatotropic (HPS) axis, with growth hormone (GH) as a central signaling molecule, plays a crucial role in regulating skeletal development. To explore whether Neanderthal-specific genetic variations in the HPS axis contributed to their physical robustness, we examined genes encoding the relevant receptors and hormones. We find that the Neanderthal growth hormone receptor (GHR) carried two amino acid changes and one deletion. When the Neanderthal GHR is expressed in a GH-dependent cell line, the cells proliferate faster than cells expressing the modern human GHR when stimulated by pituitary GH but not by placental GH. We also show that some present-day humans have inherited the gene encoding the Neanderthal GHR. These individuals tend to have more muscle mass and exhibit some craniofacial traits reminiscent of Neanderthals. Thus, aspects of Neanderthal anatomy live on in people today.

Habitat transitions are central to microbial ecology and evolution and have been extensively studied across vastly different environments, such as between saline and non-saline environments. However, microbial habitat transitions along other large-scale environmental gradients remain poorly studied. This is particularly true for transitions involving the cryosphere, despite building evidence suggesting the Cryogenian as important for evolutionary radiation. Here, we investigated ecosystem transitions and the related genomic adaptations of the cosmopolitan cryospheric Polaromonas bacterium. We constructed a pangenome from 282 high-quality genomes, sourced from glaciers, glacier-fed streams (GFSs), lakes, wetlands, groundwater, rivers, and soils. Phylogenetic reconciliation suggested that the ancestral Polaromonas genome radiated from glacier ecosystems into various downstream environments through multiple independent transitions. These transitions were likely marked by extensive horizontal gene transfer and gene loss, with mobile genetic elements such as plasmids and prophages playing key roles in genomic diversification. Predicted ancestral genomes encoded versatile metabolic and stress-response capacities, which support adaptation to fluctuating and extreme conditions in the various cryospheric habitats. Compared to the ancestral Polaromonas genome, distinct genomic signatures were associated with specific habitats: GFS lineages possess expanded stress-tolerance repertoires, glacier lineages gained chemolithotrophic and anaerobic pathways, lake and wetland genomes acquired phototrophic functions, and soil lineages expanded substrate transport and stress tolerance. Together, our findings highlight the role of genomic plasticity in the ecological success of Polaromonas and also underscore the cryosphere as a potential evolutionary cradle from which lineages dispersed and adapted to downstream aquatic and terrestrial environments.

Neural tube closure is a critical morphogenetic process in vertebrate development, and failure to close cranial regions such as the hindbrain neuropore (HNP) leads to severe congenital malformations. While mechanical forces such as actomyosin purse-string contraction and directional cell crawling have been implicated in driving HNP closure, how these forces organize local cell shape and motion to produce large-scale tissue remodeling remains poorly understood. Using live and fixed imaging of mouse embryos combined with cell-based biophysical modeling, we show that these force-generating mechanisms are insufficient to explain the reproducible patterns of cell elongation and nematic alignment observed at the HNP border. Instead, we show that local anisotropic stress and cytoskeletal organization are required to generate these patterns and promote midline cell motion. Our model captures key features of cell shape dynamics and emergent nematic order, which we confirm experimentally, including the alignment of actin fibers with cell shape and enhanced midline cell speed. Comparative analysis with chick embryos, which lack supracellular purse strings, supports a conserved link between tension generation and cellular patterning. These findings establish a physical framework connecting force generation, cell shape anisotropy, and tissue morphodynamics during epithelial gap closure.

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.

One of the features that distinguishes modern humans from our extinct relatives and ancestors is a globular shape of the braincase [1–4]. As the endocranium closely mirrors the outer shape of the brain, these differences might reflect altered neural architecture [4, 5]. However, in the absence of fossil brain tissue, the underlying neuroanatomical changes as well as their genetic bases remain elusive. To better understand the biological foundations of modern human endocranial shape, we turn to our closest extinct relatives: the Neandertals. Interbreeding between modern humans and Neandertals has resulted in introgressed fragments of Neandertal DNA in the genomes of present-day non-Africans [6, 7]. Based on shape analyses of fossil skull endocasts, we derive a measure of endocranial globularity from structural MRI scans of thousands of modern humans and study the effects of introgressed fragments of Neandertal DNA on this phenotype. We find that Neandertal alleles on chromosomes 1 and 18 are associated with reduced endocranial globularity. These alleles influence expression of two nearby genes, UBR4 and PHLPP1, which are involved in neurogenesis and myelination, respectively. Our findings show how integration of fossil skull data with archaic genomics and neuroimaging can suggest developmental mechanisms that may contribute to the unique modern human endocranial shape.