University of Vermont

cems
College of
Engineering and Mathematical Sciences

Co-Evolution of immune genes and global diversity

Release Date: 08-31-2007

Author: Dawn Marie Densmore
Email: Dawn.Densmore@uvm.edu
Phone: Array Fax: 802-656-8802

Dr. Richard
M. Single

Dr. Richard M. Single

An article by Richard M. Single, assistant professor at the University of Vermont's College of Engineering and Mathematical Sciences (CEMS), and seven other researchers entitled "Global diversity and evidence for co-evolution of KIR and HLA" recently appeared in Nature Genetics.

Two sets of immune-related genes influence resistance to infections, complications in pregnancy, outcomes after stem cell transplantation, and susceptibility and progression for hundreds of diseases such as type 1 diabetes, multiple sclerosis, rheumatoid arthritis, Hodgkin disease, tuberculosis, malaria, and AIDS. These genetic systems — the human leukocyte antigen (HLA) genes and the killer cell immunoglobulin-like receptor (KIR) genes, which reside on different chromosomes — interact to help coordinate our immune responses.

Increasing our knowledge of population-level variation in the HLA and KIR region is critical to the study of evolutionary patterns, identification of selection events, evaluation of associations with disease, research on vaccine design (e.g., HIV), and understanding the mechanisms by which disease-predisposing genes can become relatively common in a population. Knowledge of HLA and KIR variation in different ethnic groups is also vitally important in hematopoietic stem cell transplantation (e.g., for treatment of leukemia).

Given their functional relationship in the immune response, it's hypothesized that KIR and HLA may be co-evolving in humans and indeed, the population-level evidence that is described for this epistatic interaction is compelling. This paper describes the first population-based evolutionary genetic comparison of variation at these two complex genetic systems.