Life Science Paradigm Challenge

Hundreds of our genes randomly switch off either the mother's or the father's copy, making every person a 'patchwork' of different genetic expressions.

April 1, 2026

Original Paper

Autosomal Allelic Inactivation: Variable Replication and Dosage Sensitivity

Heskett, M. B.; Vouzas, A.; Johnstone, B.; Freese, K. P.; Yates, P.; Copenhaver, P. F.; Spellman, P. T.; Gilbert, D. M.; Thayer, M. J.

bioRxiv · 2025.08.13.670061

The Takeaway

Biology textbooks usually teach that both copies of our non-sex genes are active at once. This discovery reveals a massive, hidden layer of 'cellular mosaicism' where individual cells stochastically decide which parent's DNA to use.

From the abstract

Autosomal monoallelic gene expression and asynchronous replication between alleles are established features of imprinted genes and genes regulated by allelic exclusion. Inactivation/Stability Centers (I/SCs) are recently described autosomal loci that exhibit epigenetic regulation of allelic expression and replication timing, with differences that can be comparable to those observed between the active and inactive X chromosomes 1. Here we characterize >100 autosomal loci with allele-specific epig