Patin Etienne, Quintana-Murci Lluis
Institut Pasteur, Université Paris Cité, CNRS UMR 2000, Human Evolutionary Genetics Unit, Paris, France; email:
Human Genomics and Evolution, Collège de France, Paris, France.
Annu Rev Immunol. 2025 Apr;43(1):57-82. doi: 10.1146/annurev-immunol-082323-024638. Epub 2024 Dec 20.
Infections have imposed strong selection pressures throughout human evolution, making the study of natural selection's effects on immunity genes highly complementary to disease-focused research. This review discusses how ancient DNA studies, which have revolutionized evolutionary genetics, increase our understanding of the evolution of human immunity. These studies have shown that interbreeding between modern humans and Neanderthals or Denisovans has influenced present-day immune responses, particularly to viruses. Additionally, ancient genomics enables the tracking of how human immunity has evolved across cultural transitions, highlighting strong selection since the Bronze Age in Europe (<4,500 years) and potential genetic adaptations to epidemics raging during the Middle Ages and the European colonization of the Americas. Furthermore, ancient genomic studies suggest that the genetic risk for noninfectious immune disorders has gradually increased over millennia because alleles associated with increased risk for autoimmunity and inflammation once conferred resistance to infections. The challenge now is to extend these findings to diverse, non-European populations and to provide a more global understanding of the evolution of human immunity.
在整个人类进化过程中，感染施加了强大的选择压力，这使得对自然选择对免疫基因影响的研究与以疾病为重点的研究高度互补。本综述讨论了彻底改变进化遗传学的古DNA研究如何增进我们对人类免疫进化的理解。这些研究表明，现代人类与尼安德特人或丹尼索瓦人的杂交影响了当今的免疫反应，尤其是对病毒的免疫反应。此外，古代基因组学能够追踪人类免疫在不同文化过渡时期的演变，突出了自欧洲青铜时代（<4500年前）以来的强烈选择以及对中世纪肆虐的流行病和欧洲对美洲殖民期间的潜在基因适应。此外，古代基因组研究表明，数千年来，非感染性免疫疾病的遗传风险逐渐增加，因为与自身免疫和炎症风险增加相关的等位基因曾经赋予对感染的抵抗力。现在的挑战是将这些发现扩展到不同的非欧洲人群，并更全面地了解人类免疫的进化。
