Dealing with the adaptive immune system during de novo evolution of genes from intergenic sequences

Background: The adaptive immune system of vertebrates has an extraordinary potential to sense and neutralize foreign antigens entering the body. De novo evolution of genes implies that the genome itself expresses novel antigens from intergenic sequences which could cause a problem with this immune system. Peptides from these novel proteins could be presented by the MHC receptors to the cell surface and would be recognized as foreign. The respective cells would then be attacked and destroyed. Hence, de novo expressed peptides have to be introduced to the immune system as being self-peptides to avoid such autoimmune reactions. The regulation of the distinction between self and non-self occurs in the thymus and the spleen, which requires the expression of the genes in these tissues. Since the initial activation of a promotor for new intergenic transcription of a de novo gene could occur in any tissue, we should expect that the evolutionary establishment of a de novo gene in animals with an adaptive immune system should also involve expression in at least one of the tissues that confer self-recognition.