Nonsense-mediated mRNA decay is a eukaryotic pathway that degrades transcripts with premature termination codons (PTCs). In most eukaryotes, thousands of transcripts are degraded by NMD, including many important regulators of development and stress response pathways. Transcripts can be targeted to NMD by the presence of an upstream ORF or by introduction of a PTC through alternative splicing. Many factors involved in the recognition of PTCs and the destruction of NMD targets have been characterized. While some are highly conserved, others have been repeatedly lost in eukaryotic lineages. Here, I outline the factors involved in NMD, our current understanding of their interactions and how they have evolved. I outline a classification system to describe NMD pathways based on the presence/absence of key NMD factors. These types of NMD pathways exist in multiple different lineages, indicating the plasticity of the NMD pathway through recurrent losses of NMD factors during eukaryotic evolution. By classifying the NMD pathways in this way, gaps in our understanding are revealed, even within well studied organisms. Finally, I discuss the likely driving force behind the origins of the NMD pathway before the appearance of the last eukaryotic common ancestor: transposable element expansion and the consequential origin of introns.
Hairless mutation: a driving force of humanization from a human–ape common ancestor by enforcing upright walking while holding a baby with both hands
