Below is an amino acid alignment of IRGM proteins from mouse and humans. IRG proteins are immunity related GTPases and play a role in defending against intracellular parasites. When you look at the two proteins, there doesn’t seem to be much that is remarkable. The human protein is smaller, lacking about 80 of the amino acids at the C-terminal end and about 20 amino acids from the N-terminal end. The two proteins show homology over a region of about 170 amino acids, where approximately 100 of them are identical (green) and another 40 or so are similar (blue).
However, here is one other difference. The human gene was brought back from the dead after being in the genomic grave for over 20 million years.
A recent paper entitled Death and Resurrection of the Human IRGM Gene outlines an elegant case of historical reconstruction, whereby the researchers determined that the IRGM gene was disrupted by an Alu repeat integration somewhere around 40 million years ago in the lineage that led to New World and Old World monkeys. In other words, it became a non-functional pseudogene.
Then, about 20 million years later, in the common ancestor of man and apes, an ERV9 retroviral element inserted near the 5’ end of the IRGM gene and brought it back on-line. The researchers mention that it is still possible that even though the gene is expressed, it may not have a function. But they cite several lines of circumstantial evidence that indicate it is functional. I would also add that the sequence alignments show the GTPase motifs are still intact.
If it is confirmed that human IRGM is indeed functional, then we have a gene that retained a core function/sequence after experiencing 20 million years of evolution as a pseudogene. Might this be a tip of the iceberg?