Program > Browse abstracts by author > Maesen Sarah

Gene copy number variation (CNV) participates in shaping innate immunity. CNVs and subsequent gene divergence may be adaptive in host-pathogen evolution. In bats, duplication and positive selection of specific antiviral genes have contributed to bat-specific adaptation against viruses. Here, we studied the Protein Kinase R (PKR), a broad antiviral interferon-induced factor and global translation regulator, in Myotis bats to understand the dynamics of its duplication and consequences to innate immunity. 

We performed in-depth characterizations of Myotis PKR evolution at the genomic, genetic, and transcriptomic levels. We used newly-generated genomes of nine species and transcriptomics from primary fibroblasts of 15 individuals under immune stimulations. Through functional assays, we investigated paralog co-expression in antiviral restriction and translation shutdown.

We found significant variation within the PKR locus, with at least three genomic losses since the original PKR duplication. We also found enrichment of TEs in this locus and qualitative TE differences between paralogs, suggesting TEs may participate in its genomic plasticity.
Furthermore, at basal and upon stimulation by pathogen-associated molecules or interferon, transcriptomics revealed an apparent bias in endogenous gene expression between paralogs. We hypothesize that variability in expression could be attributed to distinct regulatory elements, potentially influenced by the different TE landscapes.
In exogenous assays, we further found intrinsic differences in paralog protein steady-state expression levels. Despite one copy being poorly expressed, our functional assays revealed its strong activity in shutting down protein translation and restricting viral infection. We are currently assessing whether the copies may regulate one another and perform additive functions.

The evolutionary dynamics of the Myotis PKR locus, with possible implications of TE contribution, may be the result of lineage-specific selective pressures, potentially driven by viral epidemics and costs of PKR duplication. Overall, our work may contribute to a better understanding of adaptive duplication dynamics in bat innate immunity.