Not all mutations are equal – this sentence sounds obvious, but biological reality offers surprisingly complex mechanisms behind it. Two independent groups have recently described one of those mechanisms: [1] and [2].

Mutations are commonly associated with diseases, but in the big picture of biology, they have a significant role, as they are driving force of the evolution. Roughly random modifications of DNA sequences create diversity between organisms and their populations. Because of that, evolution can’t get rid off mutations, even when they are deleterious. Instead, life invented many ways to mitigate the adverse consequences of mutations, which fall into the umbrella term: genetic robustness.

A specific mechanism, called genetic compensation response or protein feedback loop, can compensate mutations leading to total dysfunction of a protein molecule. The exact execution of pathways is reassigned to other, properly functioning genes.

According to this model, a mutation can lead to the increased expression of related genes that are themselves able to assume the function of the mutated gene.

“Genetic compensation triggered by mutant mRNA degradation” M. El-Borosy et al. 2019

A surprising consequence of the mechanism is a large difference between mutations leading to changes in proteins, and mutations changing gene activation. Silencing of a gene can be more severe than (seemingly damaging) direct mutation shortening a protein molecule – as a consequence of premature termination codon.