Immune system diversity and pathogen evolution
Background and past work
Immune system genes include the two most diverse gene families in the human genome: human leukocyte antigens (HLAs, also known as major histocompatibility complex genes MHCs) and Killer-cell Immunglobulin-like Receptors (KIRs). Immune system genes affect the types of immune response your body can make, and differences between people's immune system genes are the reason that organ transplantation requires careful matching between donor and recipient.
We have shown that pathogen selection can account for the genomic organisation of HLAs (Penman et al 2013Link opens in a new window), and that a combination of pathogen selection and reproductive selection could have shaped the population genetics of human KIRs (Penman et al 2016Link opens in a new window). As part of his PhD work, Connor White recently showed how the combined effects of HLA diversity and pathogen diversity may mean we miss important HLA effects in case control studies of HLAs and infection (White et al 2020Link opens in a new window).
Thanks to funding from an Academy of Medical Sciences Springboard award, we are (i) developing new models to understand how infectious diseases evolve when they spread within HLA-diverse populations, and (ii) analysing combined datasets of HLA diversity and pathogen diversity to look for evidence of HLA/pathogen co-evolution. We are first focusing on Plasmodium falciparum malaria, since it has a long history of causing immense mortality in human populations. Our previous results (Penman and Gupta 2018) indicate the patterns HLA/pathogen co-evolution is likely to create in population genetic datasets; identifying such signatures in malaria data will suggest new malaria vaccine targets. Alberto Torcello recently joined the group as a postdoc to pursue this project.
Group members Connor White and Arthur Margolis are both working on questions of immunogenetics and evolution - please check out their individual project pages to find out more.