🎙️ Episode Title: What Makes Us Human? Genetics from Neandertals to Now

🧬 In this episode of Base by Base, we travel back in time—over 600,000 years—to explore the genomic storylines of Neandertals, Denisovans, and modern humans. Published in Cell by Hugo Zeberg, Mattias Jakobsson, and Nobel Laureate Svante Pääbo, this comprehensive review deciphers the evolutionary divergences that defined—and continue to define—our species.

By comparing high-quality genomes from extinct and extant human lineages, the authors provide a sweeping analysis of the genetic variants that shaped brain function, metabolism, immunity, reproduction, and adaptation to diverse environments.

🔍 Key insights include:

• Archaic legacy: 2% of the genome in non-African individuals today comes from Neandertals; in Oceania, over 5% derives from Denisovans.

• Disease and adaptation: Some Neandertal variants increase risk for conditions like severe COVID-19 and autoimmune disease—yet others provide resistance to infections like Helicobacter pylori and HIV.

• Denisovan traces: Modern Tibetan populations inherited a Denisovan variant in EPAS1, aiding adaptation to high altitudes.

• Brain development: Modern human-specific changes in genes like TKTL1, KNL1, and KIF18A influence early neurogenesis and chromosomal segregation—potential contributors to our cognitive evolution.

• The combinatorial human: Rather than a single “modern” genetic signature, humans today carry a mosaic of derived and ancestral alleles—defining our species by combinations of variants, not absolutes.

• Experimental revival: Using CRISPR, organoids, and mouse models, researchers are now resurrecting archaic variants to study their effects in human cells and model organisms.

• Rewriting assumptions: Several variants thought to be exclusive to modern humans are found in ancestral form in present-day populations—especially in Africa and the Philippines.

This landmark review redefines human uniqueness through a genomic lens, not as a checklist of fixed traits, but as a dynamic ensemble of evolutionary possibilities. It’s a must-listen for anyone intrigued by how ancient DNA continues to shape our biology, health, and identity.

📖 Reference:
Zeberg, H., Jakobsson, M., & Pääbo, S. (2024). The genetic changes that shaped Neandertals, Denisovans, and modern humans. Cell, 187. https://doi.org/10.1016/j.cell.2023.12.029

📜 License:
This episode is based on an open access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/