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Letter

Millions of Years of Evolution Preserved: A Comprehensive Catalog of the Processed Pseudogenes in the Human Genome

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8114, USA

Processed pseudogenes were created by reverse-transcription of mRNAs; they provide snapshots of ancient genes existing millions of years ago in the genome. To find them in the present-day human, we developed a pipeline using features such as intron-absence, frame-disruption, polyadenylation, and truncation. This has enabled us to identify in recent genome drafts 8000 processed pseudogenes (distributed from http://pseudogene.org). Overall, processed pseudogenes are very similar to their closest corresponding human gene, being 94% complete in coding regions, with sequence similarity of 75% for amino acids and 86% for nucleotides. Their chromosomal distribution appears random and dispersed, with the numbers on chromosomes proportional to length, suggesting sustained "bombardment" over evolution. However, it does vary with GC-content: Processed pseudogenes occur mostly in intermediate GC-content regions. This is similar to Alus but contrasts with functional genes and L1-repeats. Pseudogenes, moreover, have age profiles similar to Alus. The number of pseudogenes associated with a given gene follows a power-law relationship, with a few genes giving rise to many pseudogenes and most giving rise to few. The prevalence of processed pseudogenes agrees well with germ-line gene expression. Highly expressed ribosomal proteins account for 20% of the total. Other notables include cyclophilin-A, keratin, GAPDH, and cytochrome c.

¹ Corresponding author.
E-MAIL Mark.Gerstein{at}yale.edu; FAX (360) 838-7861.

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