If a gene is transcribed and translated, but there are some mutations at key residues of the protein to make the protein non-functional or very unstable (with very short half life), do we call these kind of gene pseudogene? If it is not, it will be less meaningful for me to classify them, because it is not under the same evolutional pressure as functional genes. If it is, computer algorithms may have difficulty to identify them.
This is a very interesting question. The definition of "gene" and "pseudogene" is extremely fuzzy. Currently, our pipeline will not call this a pseudogene because we primarily look for frame-shifts and nonsense mutations. We can identify processed pseudogenes which don't have frame-shifts or nonsense mutaions, specifically pseudogenes of multiexon genes that will appear as a single exon retrotransposed gene. We don't have a clear way of differentiating between a functional retrogene and pseudogene. We simply flag it is a processed pseudogene. If the gene of interest has many exons and this structure is retained in the non-functional entities, we will not call it a pseudogene unless we detect a frame-shift or a nonsense mutation. But we are constantly adding new features to our pipeline and will have a discussion with Prof. Gerstein and the rest of the team about this aspect.