Microevolution of Human Toll-Like Receptors in Central Asia During Bronze and Iron Ages

Abstract

The Toll-like receptors (TLRs) are an integral component of human immune defense because they act as first-responders to infection. Previous research has documented the presence of archaically-introgressed sequences of DNA into the TLR10-6-1 cluster (Deschamps et al., 2016 & Dannemann et al., 2016). This genetic region has also been suggested to be a hotspot for selection in both contemporary and ancient Eurasian populations (Barreiro et al., 2009 & Mathieson et al., 2015). Furthermore, ancient trains of Salmonella, Tuberculosis, and Plague were present on the Eurasian landmass, all of which would incite response from the TLRs (Andrades Valtueña et al., 2022; Rasmussen et al., 2015; Key et al., 2020; Wu et al., 2020; Hajam et al., 2017; Caroff and Karibian et al., 2003; Strahl and Errington 2017; Mukherjee et al., 2014). Allen Ancient DNA Resource was used to access genotype data on five archaic TLR SNPs from 298 individuals who lived between 7922 and 1109 BP is used to examine their temporal and geographic distribution (Mallick and Reich, 2024 & Mallick et al., 2024). Here, hypotheses are tested to determine whether lifestyle, time period, a combination of the two, or geography predict the presence of archaic TLR SNPs. The aim of this study was also to assess whether that distribution reflects microevolutionary change in the direction of drift or selection. A peripheral aim of this study was to answer whether that distribution is a result of adaptation to pathogens. It is concluded that the temporal and geographic distribution of these SNPs is both stochastic and does not reflect a signal of selection nor are lifestyle, time-period, a combination of the two, or geography predict the presence of archaic TLR SNPs.