The footprint of polygenic adaptation on stress-responsive cis-regulatory divergence in the Arabidopsis genus

Adaptation of a complex trait often requires the accumulation of many modifications to finely tune its underpinning molecular components to novel environmental requirements. The investigation of cis-acting regulatory modifications can be used to pinpoint molecular systems partaking in such complex adaptations. Here, we identify cis-acting modifications with the help of an interspecific crossing scheme designed to distinguish modifications derived in each of the two sister species, Arabidopsis halleri and A. lyrata Allele-specific expression levels were assessed in three environmental conditions chosen to reflect interspecific ecological differences: cold exposure, dehydration, and standard conditions. The functions described by Gene Ontology categories enriched in cis-acting mutations are markedly different in A. halleri and A. lyrata, suggesting that polygenic adaptation reshaped distinct polygenic molecular functions in the two species. In the A. halleri lineage, an excess of cis-acting changes affecting metal transport and homeostasis was observed, confirming that the well-known heavy metal tolerance of this species is the result of polygenic selection. In A. lyrata, we find a marked excess of cis-acting changes among genes showing a transcriptional response to cold stress in the outgroup species A. thaliana The adaptive relevance of these changes will have to be validated. We finally observed that polygenic molecular functions enriched in derived cis-acting changes are more constrained at the amino acid level. Using the distribution of cis-acting variation to tackle the polygenic basis of adaptation thus reveals the contribution of mutations of small effect to Darwinian adaptation.