The team also found that the Rps23r1 gene, whose human counterpart has not yet been identified, was created through a process called retroposition, in which a gene is duplicated through the reverse transcription (or reading) of mRNA and the duplicate is placed in a different location in the cell's DNA. Although most retroposition events result in non-functional duplicates (called pseudogenes) , in rare cases, retroposed genes, like Rps23r1, can become functional.

"From the point of view of treating Alzheimer's disease, if we can express the mouse gene in human brain cells, we may be able to control the buildup of amyloid beta and tau neurofibrillary tangles," said Dr. Xu. "From an evolutionary point of view, we have found an example of a retroposed gene that took on a completely new function."

Dr. Xu and colleagues used a technology called random homozygous gene perturbation to search for genes that regulate amyloid beta generation. This allowed the team to identify the Rps23r1 gene and found that the RPS23R1 protein it encodes can interact with a protein called adenylate cyclase that stimulates a second protein called protein kinase A, which inhibits GSK-3 activity. The effects of RPS23R1 on reducing amyloid beta levels and tau phosphorylation were corroborated in a transgenic Alzheimer's disease mouse model. The team subsequently determined that Rps23r1 is a reverse-transcribed version of the mouse ribosomal protein S23 (Rps23) gene, which is nearly identical to the human Rps23 gene.

Source: Burnham Institute