Transcriptional adaptation influences buffering among essential paralog gene families
- 1Fred Hutchinson Cancer Center
Abstract
Buffering among paralogous genes is a well-described phenomenon in which genetic redundancy provides genetic robustness. Shared function among paralogs allows for a compensation effect when one or more paralog family genes are inactivated. Considering the role of transcriptional adaptation in influencing gene expression among highly homologous genes, we sought to identify whether transcriptional adaptation has a role in paralog buffering. We performed Perturb-seq of 110 paralog gene knockouts and assessed compensatory gene expression effects among paralogs as well as at the whole transcriptome level. This analysis identified six paralog pairs that undergo a transcriptional adaptation following CRISPR-mediated loss of one paralog in the pair. Further, we found that the upregulation of TIA1 following paralog TIAL1 loss requires nonsense-mediated decay, and active nuclear import via the importin IPO8. These data provide a comprehensive evaluation of transcriptional adaptation and show that transcriptional adaptation is recurrent but not pervasive among paralogous human genes.
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BibTeX
@misc{obrien2026transcriptional,
title = {{Transcriptional adaptation influences buffering among essential paralog gene families}},
author = {S. O'Brien and M. Fujimoto and A. R. Lowe and A. H. Berger},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.24.754217},
url = {https://www.biorxiv.org/content/10.64898/2026.09.24.754217v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Transcriptional adaptation influences buffering among essential paralog gene families
AU - S. O'Brien
AU - M. Fujimoto
AU - A. R. Lowe
AU - A. H. Berger
PY - 2026
DA - 2026/09/24
PB - bioRxiv
DO - 10.64898/2026.09.24.754217
UR - https://www.biorxiv.org/content/10.64898/2026.09.24.754217v1
AB - Buffering among paralogous genes is a well-described phenomenon in which genetic redundancy provides genetic robustness. Shared function among paralogs allows for a compensation effect when one or more paralog family genes are inactivated. Considering the role of transcriptional adaptation in influencing gene expression among highly homologous genes, we sought to identify whether transcriptional adaptation has a role in paralog buffering. We performed Perturb-seq of 110 paralog gene knockouts and assessed compensatory gene expression effects among paralogs as well as at the whole transcriptome level. This analysis identified six paralog pairs that undergo a transcriptional adaptation following CRISPR-mediated loss of one paralog in the pair. Further, we found that the upregulation of TIA1 following paralog TIAL1 loss requires nonsense-mediated decay, and active nuclear import via the importin IPO8. These data provide a comprehensive evaluation of transcriptional adaptation and show that transcriptional adaptation is recurrent but not pervasive among paralogous human genes.
ER -