Pseudogenes: Four Decades of Discovery

A pseudogene is defined as a genomic DNA sequence that looks like a mutated or truncated version of a known functional gene. Nearly four decades since their first discovery it has been estimated that between ~12,000 and ~20,000 pseudogenes exist in the human genome. Early efforts to characterize functions for pseudogenes were unsuccessful, thus they were considered functionless relics of evolutionary selection, junk DNA or genetic fossils. Remarkably, an increasing number of pseudogenes have been reported to be expressed as RNA transcripts above and beyond levels considered accidental or spurious transcription. There is emerging evidence that some expressed pseudogene transcripts have biological functions and should be defined as a subclass of functional long noncoding RNAs (lncRNA). In this introductory chapter, I briefly summarize the history and the current knowledge of pseudogenes, and highlight the emerging functions of some pseudogenes in human biology and disease. This second iteration of Pseudogenes in Methods in Molecular Biology highlights new methodological approaches to investigate this intriguing family of lncRNAs and the extent of their biological function.