A priority of our lab is to design and validate novel approaches for the identification of molecular targets of natural selection. Much of our previous work has focused on large effect mutations or candidate genes (Kronholm et al. Mol Biol Evol 2012, Vetter et al. Mol Biol Evol 2012). Mutations of small effect, however, also play a role in adaptation, because they are numerous and many complex traits have a highly polygenic (sometimes called omnigenic) basis (reviewed in Falke et al. Cur Op Genet 2013). This requires approaching small effect mutations not as singular events but as a population distributed in groups of functionally connected genes. The prediction is that natural selection will enrich the molecular systems controlling adaptive phenotypes in independent mutations. In our lab, we take a special interest in cis-regulatory mutations, because i) they can be easily typed throughout the genome by measuring allele-specific expression levels in F1 hybrids and ii) we can identify the ones that are active in ecologically relevant conditions – e.g. after cold exposure, in the presence of drought stress etc… (He et al. Mol Biol Evol 2012). 

Cis-regulatory mutations form a large population of small effect mutations

We have used interspecific F1 hybrids to map cis-regulatory variants throughout the genome (He et al. Mol Biol Evol 2012, He et al. Mol Biol Evol 2016). This work demonstrated that cis-regulatory mutations form a large pool of mutations. Their distribution throughout the genome can be quantified and analyzed. We have also shown that gene expression in F1 interspecific hybrids is not massively disturbed, thus confirming that F1 hybrids form a useful tool to infer some of the genetic basis of variation in expression (Göbel et al. Gen Biol Evol 2018).

The distribution of cis-regulatory mutations can be used to highlight footprints of selection on molecular systems

Using diverse interspecific hybrids, we drew the genomic distribution of cis-regulatory differences accumulated since divergence of the two sister-species A. halleri and A. lyrata in response to drought and cold. Our results highlight the cellular systems important for lineage specific evolution of the response to these stresses, which differentiate the ecology of the two sister species (He, et al. 2016). We are currently collaborating with Prof. Andreas Weber (CEPLAS) and Prof. Andreas Beyer (CECAD) to dissect the polygenic basis of stress responses in the Arabidopsis genus.

Does local adaptation recruit similar or different molecular modifications in plants?

Arabidopsis thaliana and A. lyrata are two closely related plant species with populations found at different latitudes in Southern, Central and/or Northern Europe. Within each species, populations are genetically and phenotypically different, showing some degree of local adaptation. These populations have to adjust their development to the distinct climatic conditions they experience. What is the genetic basis of these changes? Which molecular systems did natural selection fine-tune to reach optimal fitness locally? Did adaptive processes recruit small effect mutations? Do they affect similar gene pathways in the two species?

Since September 2015, we have initiated a large project to explore intraspecific variation in cis-regulation (ERC Consolidator Grant Adaptoscope). The goal of the project is to determine the extent of parallel evolution in cis-regulation in the two close relatives A. lyrata and A. thaliana, during their range expansion to Northern latitudes.