Pseudogenes in the ENCODE regions: Consensus annotation, analysis of transcription, and evolution

Abstract

Arising from either retrotransposition or genomic duplication of functional genes, pseudogenes are "genomic fossils" valuable for exploring the dynamics and evolution of genes and genomes. Pseudogene identification is an important problem in computational genomics, and is also critical for obtaining an accurate picture of a genome's structure and function. However, no consensus computational scheme for defining and detecting pseudogenes has been developed thus far. As part of the ENCyclopedia Of DNA Elements (ENCODE) project, we have compared several distinct pseudogene annotation strategies and found that different approaches and parameters often resulted in rather distinct sets of pseudogenes. We subsequently developed a consensus approach for annotating pseudogenes (derived from protein coding genes) in the ENCODE regions, resulting in 201 pseudogenes, two-thirds of which originated from retrotransposition. A survey of orthologs for these pseudogenes in 28 vertebrate genomes showed that a significant fraction (∼80%) of the processed pseudogenes are primate-specific sequences, highlighting the increasing retrotransposition activity in primates. Analysis of sequence conservation and variation also demonstrated that most pseudogenes evolve neutrally, and processed pseudogenes appear to have lost their coding potential immediately or soon after their emergence. In order to explore the functional implication of pseudogene prevalence, we have extensively examined the transcriptional activity of the ENCODE pseudogenes. We performed systematic series of pseudogene-specific RACE analyses. These, together with complementary evidence derived from tiling microarrays and high throughput sequencing, demonstrated that at least a fifth of the 201 pseudogenes are transcribed in one or more cell lines or tissues.

The CD1/CD2 marker for specific detection of Colletotrichum lindemuthianum is an iron transporter pseudogene

“…Processed pseudogenes are retrotransposed into the genome via an RNA intermediate and therefore lack introns, may possess relics of a poly(A) tail and are often flanked by target-site duplications (Zheng et al, 2007). Nonprocessed pseudogenes, on the other hand, arise from non-homologous recombination events.…”

Detection of Imprinted Genes by Single-Cell Allele-Specific Gene Expression

“…However, we excluded multiple mapped reads and intronic SNVs that confound pseudogenes with their parental genes. 28 Variants falling inside repeated regions such as segmental duplications or repeats (according to RepeatMasker) were filtered out (Table S2). All experiments were performed using the manufacturer's recommended protocols without modifications.…”

Genome-Wide Analysis of the Arabidopsis Replication Timing Program

“…Pseudogenes are enriched in ML segments. This 286 may be due in part to the association of "processed pseudogenes," the products of 287 retrotransposition events (Zheng et al, 2007), with TE-rich pericentromeric regions that replicate 288 in ML (Fig. 4A).…”