Unannotated splicing and translation of non-canonical open reading frames generate a diverse repertoire of cryptic proteins. Most are rapidly degraded, rendering them possible MHC-I substrates. Yet, a subpopulation can adopt stable structures and impart advantageous functions. This dichotomy both expands the antigen landscape and provides a framework for protein evolution.
ABSTRACT
The widespread translation of cryptic proteins derived from the non-coding genome expands the complexity of the human proteome. A vast majority of cryptic proteins are expressed at low levels, rapidly degraded and efficiently presented on class I major histocompatibility complexes (MHC-I). On the other hand, some cryptic proteins are stable and functional and may integrate into the proteome through ongoing selective pressures. Herein, we propose a model in which the translation of cryptic proteins increases the diversity of functional proteins on which evolution can act and, during this trial-and-error process, provides a valuable source of antigens for immunosurveillance.