Abstract
Evidence indicates that transposable elements (TEs) can contribute to the evolution of new traits, despite often being considered deleterious. In vertebrates, some KRAB-ZNF proteins repress TEs, offering genomic protection. Notably, KRAB-ZNF genes evolve rapidly and exhibit diverse expression patterns in primate brains, where TEs remain active. This prompts questions about their interactions in primate brains and potential roles in human brain evolution and disease. For a systematic comparative analysis of TE interactions with other genes, we developed the tool TEKRABber, and focused on strong and experimentally validated cases. Our bipartite network analysis revealed significantly more interactions between KRAB-ZNF genes and TEs in humans than in other primates, especially with recently evolved, i.e. Simiiformes specific, TEs. Notably, ZNF528, under positive selection in humans, shows numerous human-specific TE interactions. Most negative interactions in our network, indicative of repression by KRAB-ZNF proteins, entail Alu TEs, while links to other TEs are generally positive. In Alzheimer’s patients, a subnetwork involving 21 interactions with an Alu module appears diminished or lost. Our findings suggest that KRAB-ZNF and TE interactions vary across TE families, have increased throughout human evolution, and may influence susceptibility to Alzheimer’s disease.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
1. Provide additional visualization for one-to-one correlations results. 2. Add additional analysis to demonstrate the differences before and after scaling the data. 3. Add more evidence on the reason using a binary evolutionary age classification.
https://www.bioconductor.org/packages/release/bioc/html/TEKRABber.html
