Identification and analysis of unitary pseudogenes: historic and contemporary gene losses in humans and other primates

We have developed a pipeline to detect human unitary pseudogenes through analyzing the global inventory of orthologs between the human genome and its mammalian relatives. We focus on gene losses along the human lineage after the divergence from rodents about 75 million years ago. In total, we identify 76 unitary pseudogenes, including previously annotated ones, and many novel ones. By comparing each of these to its functioning ortholog in other mammals, we can approximately date the creation of each unitary pseudogene (that is, the gene 'death date') and show that for our group of 76, the functional genes appear to be disabled at a fairly uniform rate throughout primate evolution - not all at once, correlated, for instance, with the 'Alu burst'. Furthermore, we identify 11 unitary pseudogenes that are polymorphic - that is, they have both nonfunctional and functional alleles currently segregating in the human population. Comparing them with their orthologs in other primates, we find that two of them are in fact pseudogenes in non-human primates, suggesting that they represent cases of a gene being resurrected in the human lineage.This analysis of unitary pseudogenes provides insights into the evolutionary constraints faced by different organisms and the timescales of functional gene loss in humans.Pseudogenes (ψ) are nongenic DNA segments that exhibit a high degree of sequence similarity to functional genes but contain disruptive defects. The initial pseudogenization of a functional gene is most likely a single mutagenic event that results in premature stop codons, abolished splice junctions, shifts to the coding frame, or impaired transcriptional regulatory sequences. Most pseudogenes are disabled copies of a functional 'parent' gene and can be classified as either processed or duplicated pseudogenes depending on whether they are generated by the retro-transposition of processed mRNA transcripts or the duplication of gene-containing DNA segments in the genome. Rece