Researchers find repeated genetic duplications and genetic diversification in protein kinase R in mouse-eared bats

PKR has been the target of strong diverse positive selection and original duplication in bats.(A) Sites under positive selection in mammalian protein kinase R (PKR). The graphic panels represent the posterior probabilities of positive selection [Bayes empirical Bayes (BEB)] (there axis) in the M2 model (ω > 1) for each codon (X axis). Red bars indicate sites with a BEB > 0.95. The numbers in parentheses represent the total number of species analyzed. Viral antagonists: herpes virus US11, influenza A virus (IAV) NS1A, poxvirus E3 and K3 (green striped boxes), hepatitis C virus (HCV) NS5A and human immunodeficiency virus Tat, which interact directly with the PKR. (B) Bat PKR maximum likelihood phylogeny indicating branches under positive selection (P < 0.05, in red). Parentheses, estimated values ​​of ω and proportion of sites under positive selection. Scale bar, number of substitutions per site. (VS) Maximum likelihood phylogeny Myotis PKR paralog transcripts, with Murine aura, E. brown, Boreal Lasiurusand Pipistrellus kuhlii as external groups (collapsed for viewing). PKR1L and PKR2L can be paralogs or splice variants of PKR1 and PKR2, respectively. Colors indicate isolated duplicate PKRs of an individual. Bootstrap values ​​≥0.7 are displayed. Scale bar, number of substitutions per site. (D) Canonical place of EIF2AK2/PKR in mammals. The EIF2AK2 genes (black and gray arrows), the EIF2AK2 pseudogene (striped arrow) and adjacent genes (white arrows) are shown. The genomic coordinates are indicated. (E) Expression pattern of PKR paralogs during basal and IFNα treatment of Mr. velifer fibroblasts. The boxplots represent the number of reads in the log_ten scale for each condition and copy of PKR (for exons found in both genes). Credit: Scientists progress (2022). DOI: 10.1126/sciadv.add7540

An international team of researchers has found evidence of repeated genomic duplications and genetic diversification of protein kinase R (PKR) in mouse-eared bats. In their article published in the journal Scientists progressthe group describes their genomic study of several species of mouse-eared bats and the sequencing of 15 of them.

Previous research has shown that bats can harbor many viral infections that do not harm them – this is one of the reasons they have been identified as vectors of viruses that spread to other animals and/or or humans. In this new effort, researchers sought to learn more about why bats can remain unharmed when infected with viruses that harm most other mammals.

The team’s work mainly focused on PKR, a protein encoded by the EIF2AK2 gene. Previous research has shown that it is an important part of immune responses to viruses in mammals. To learn more about how it works in bats compared to other mammals, the researchers looked at the genetic sequences of 33 species of mouse-eared bats.

They focused more specifically on differences in EIF2AK2, which drive differences in PKR, which in turn account for different virus-fighting abilities. The team also sequenced the genomes of 15 of the species to get a broader perspective on the role played by EIF2AK2 in the history of mouse-eared bats.

The researchers found evidence of what they describe as an arms race between EIF2AK2 and various viruses. And as part of this arms race, at some point, a duplication appeared. EIF2AK2 began to appear twice in the genome, resulting in two different types of PKR being made in each bat studied. And both versions didn’t just double down on virus removal; they were slightly different, allowing the bat that harbored them to fight off a virus in two ways. And that, the researchers say, is likely why bats are able to harbor viruses without getting sick.

The researchers also found some species that had more than two copies of EIF2AK2 and, in some cases, other genes very similar to EIF2AK2. Either way, this likely makes bats even more capable of fighting off viruses. They also noted that such duplications have so far only been found in bats.

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