Exploring the contribution of social inequality to the evolution of the Mycobacterium tuberculosis complex across five millennia

Tuberculosis (TB) is globally the top cause of death by an infectious agent but disproportionately affects those in poor countries without access to adequate nutrition. TB is today an infection of inequality; was it always, and how has this shaped its evolutionary trajectory from environmental microbe to obligate pathogen? This fellowship combines ancient DNA and paleopathology to uncover the extinct genomic architecture of the wider Mycobacterium tuberculosis complex (MTBC) to address a fundamental question in evolutionary medicine and biology: how do obligate pathogens evolve in response to human behaviour? This project focuses on recovering ancient MTBC genomes and skeletal evidence for malnutrition in Britain across five millennia. By integrating both datasets, my proposal will examine the evolution of the MTBC over two scales: (1) broad diachronic trends in MTBC adaptation, lineage spread, and replacement and (2) a local biology perspective on resource inequity and TB burden within past communities. This unparalleled time series approach will determine if gene loss (i.e. adaptation) occurred linearly through time or rapidly during periods when people were most susceptible to infections. The recovery of contemporaneous MTBC genomes from single sites will reveal trends in virulence, transmissibility, and the role of spillovers during MTBC evolution.