Current Areas of Research
Evolution of an optimal immune response
The vertebrate immune system combines a plethora of specific and unspecific mechanisms to defend the body against invading (and coevolving) pathogens. The more diverse the immune response, the broader the spectrum of recognized pathogens. However, a too diverse immune response may also increase the risk of self-reactivity, in humans known as autoimmune diseases. Hints for such a trade-off can be observed at multiple levels in the immune system, but is most apparent at the Major Histocompatibility Complex (MHC). The MHC encodes highly polymorphic molecules that each recognize specific pathogens, but every individual carries only a very limited number of these genes. We are interested in the processes and constraints that increase or limit and thus shape the individual genetic diversity at the MHC. A current focus is the link between MHC diversity and autoimmunity in human populations, but ultimately we are also interested in a broader perspective and are exploring in which ways diversity at the MHC interacts with other immune genes and the genetic background. For this work we are mostly relying on computational tools and approaches.
Lenz (2011) PNAS
Eizaguirre, Lenz, et al. (2012) Ecol Lett
Lenz, Deutsch, et al. (2015) Nat Genetics
McLaren et al. (2015) PNAS
Arora et al. (2019) PNAS
Evolutionary Genomics of the Major Histocompatibility Complex (MHC)
The MHC is characterized by exceptional genetic and genomic properties, including a vast number of protein-coding alleles, gene copy number variation, and both extensive linkage disequilibrium but also recombination hot spots. It is assumed that these properties are to a large extent the result of natural selection, but very little is known about the processes ultimately responsible for the observed patterns. We are exploring the structural organization and patterns of diversity in the MHC region within and between natural populations (mainly sticklebacks and humans), with the ultimate goal to identify genetic, genomic, and environmental factors that contribute to the genomic organisation of the MHC. This work includes computational approaches as well as genetic and genomic techniques, including next generation sequencing.
Lenz et al. (2009) BMC Evol Biol
Lenz (2011) Evolution
Lenz et al. (2013) Evolution
Chain et al. (2014) PLoS Genetics
Lenz et al. (2016) Mol Biol Evol
Human population genetics and genomics
Pathogen-mediated selection has repeatedly been suggested as one of the major drivers for human evolution, with immune genes frequently showing the strongest signatures of selection and dominating any outlier test for genetic divergence between populations. The increasing genomic resources from human populations and the availability of epidemiological data provides unparalleled opportunities to explore local immunogenetic adaptation in humans. However, contemporary data limits our ability to infer selection processes in the past. We are therefore also investigating immunogenetic evolution in historical populations, focusing on drastic epidemiological events in modern human history.
Savova et al. (2016) Nat Genetics
Calvignac-Spencer & Lenz (2017) BioEssays
Krause-Kyora et al. (2018) Nat Communications
Pierini & Lenz (2018) Mol Biol Evol