An evolutionary medicine perspective on Neandertal extinction.

Area of Science:

• Paleogenomics
• Human Evolution
• Immunology

Background:

• The extinction of Neandertals is debated, with the "differential pathogen resistance" model suggesting novel diseases transmitted by modern humans played a role.
• Genetic admixture confirms Neandertals and modern humans coexisted and interacted, potentially exposing Neandertals to new pathogens.
• Neandertal nuclear genomes show lower genetic diversity than modern humans, possibly impacting their immune system's ability to combat new diseases.

Purpose of the Study:

• To compare genetic diversity in immune system genes between Neandertals and modern human populations (African, European, Asian).
• To investigate if lower Neandertal genetic diversity in pathogen defense genes supports the differential pathogen resistance extinction model.

Main Methods:

• Analysis of exome sequencing data from three individuals (six chromosomes) per population.
• Comparison of genetic diversity (nonsynonymous polymorphisms) in 73 innate immune system genes.
• Assessment of genetic diversity in balancing selection candidate genes and 12 Major Histocompatibility Complex (MHC) genes.

Main Results:

• Neandertals exhibited 31-39% lower genetic diversity in innate immune genes compared to modern humans.
• Neandertal genetic diversity was also low in primate balancing selection candidate genes.
• Conversely, Neandertals displayed similar or higher genetic diversity in 12 Major Histocompatibility Complex (MHC) genes.

Conclusions:

• Neandertals may have been more susceptible to certain novel pathogens due to reduced genetic diversity in some immune genes.
• Differential pathogen resistance is a plausible contributing factor to Neandertal extinction, but the findings are not universally consistent with this model.
• The complex genetic diversity patterns in Neandertal immune genes highlight the multifaceted nature of their extinction.