RetrogeneDB–a database of plant and animal retrocopies

Abstract For a long time, retrocopies were considered ‘junk DNA’, but numerous studies have shown that retrocopies may gain functionality and become so-called retrogenes. Retrogenes may code fully functional proteins that coexist with parental gene products or may even replace them. Retrocopies may also function as regulatory RNAs and, for example, become a source of small interfering RNAs, act as trans natural antisense transcripts or as alternative targets for miRNAs. Numerous researchers have emphasized that retrogenes play a crucial role in various organisms’ developmental stages and diseases. Despite the ever-growing evidence of the importance of retrocopies, resources dedicated to retroposition are very limited. Here, we report an update of the RetrogeneDB, which, to the best of our knowledge, is the largest database dedicated to retrocopies. It provides annotations of 86 458 retrocopies in 62 animal and 37 plant species. The database contains information about the retrocopies’ localization, open reading frame conservation, expression, RNA Polymerase II activity and the alternative transcription start site studies. Orthologous relationships between retrogenes were also determined, which made retrocopy conservation studies much more valuable. Additionally, based on the RNA-Seq data from the Geuvadis project, the expression levels of retrocopies were estimated in a total of 50 individuals from 5 human populations. The information is now presented in a new, more user-friendly web interface, with easy access to the source data, which may be used for the downstream analysis. RetrogeneDB is freely available at http://yeti.amu.edu.pl/retrogenedb. Database URL: http://yeti.amu.edu.pl/retrogenedb Secondary database URL: http://rhesus.amu.edu.pl/retrogenedb

[1]  Terrence S. Furey,et al.  The UCSC Genome Browser Database: update 2006 , 2005, Nucleic Acids Res..

[2]  Data production leads,et al.  An integrated encyclopedia of DNA elements in the human genome , 2012 .

[3]  Gregory D. Schuler,et al.  Database resources of the National Center for Biotechnology Information: update , 2004, Nucleic acids research.

[4]  Adel Khelifi,et al.  HOPPSIGEN: a database of human and mouse processed pseudogenes , 2005, Nucleic Acids Res..

[5]  Mouchiroud Dominique,et al.  HOPPSIGEN: a database of human and mouse processed pseudogenes , 2004, Nucleic Acids Res..

[6]  David Haussler,et al.  The UCSC Genome Browser database: update 2010 , 2009, Nucleic Acids Res..

[7]  E. M. Muro,et al.  Pseudogenes as an alternative source of natural antisense transcripts , 2010, BMC Evolutionary Biology.

[8]  Aaron R. Quinlan,et al.  Bioinformatics Applications Note Genome Analysis Bedtools: a Flexible Suite of Utilities for Comparing Genomic Features , 2022 .

[9]  J. Brosius,et al.  Retroposons--seeds of evolution. , 1991, Science.

[10]  Oliver H. Tam,et al.  Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes , 2008, Nature.

[11]  K. Staras,et al.  Axonal trafficking of an antisense RNA transcribed from a pseudogene is regulated by classical conditioning , 2013, Scientific Reports.

[12]  Lukas Wagner,et al.  A Greedy Algorithm for Aligning DNA Sequences , 2000, J. Comput. Biol..

[13]  Dan M. Bolser,et al.  Ensembl Genomes 2016: more genomes, more complexity , 2015, Nucleic Acids Res..

[14]  Xuefei Shi,et al.  Pseudogene-expressed RNAs: a new frontier in cancers , 2016, Tumor Biology.

[15]  A. Reymond,et al.  Emergence of Young Human Genes after a Burst of Retroposition in Primates , 2005, PLoS biology.

[16]  David J. Arenillas,et al.  JASPAR 2016: a major expansion and update of the open-access database of transcription factor binding profiles , 2015, Nucleic Acids Res..

[17]  Derek W Wright,et al.  Gateways to the FANTOM5 promoter level mammalian expression atlas , 2015, Genome Biology.

[18]  W. J. Kent,et al.  BLAT--the BLAST-like alignment tool. , 2002, Genome research.

[19]  Evan Bolton,et al.  Database resources of the National Center for Biotechnology Information , 2017, Nucleic Acids Res..

[20]  Beth Israel,et al.  Decision letter: Replication Study: A coding-independent function of gene and pseudogene mRNAs regulates tumour biology , 2010 .

[21]  Peng Wang,et al.  miRSponge: a manually curated database for experimentally supported miRNA sponges and ceRNAs , 2015, Database J. Biol. Databases Curation.

[22]  Damian Szklarczyk,et al.  “Orphan” Retrogenes in the Human Genome , 2012, Molecular biology and evolution.

[23]  Pedro G. Ferreira,et al.  Transcriptome and genome sequencing uncovers functional variation in humans , 2013, Nature.

[24]  I. Rogozin,et al.  Primate and Rodent Specific Intron Gains and the Origin of Retrogenes with Splice Variants , 2010, Molecular biology and evolution.

[25]  Terrence S. Furey,et al.  The UCSC Table Browser data retrieval tool , 2004, Nucleic Acids Res..

[26]  Y. Sakaki,et al.  Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes , 2008, Nature.

[27]  Tim J. P. Hubbard,et al.  Dalliance: interactive genome viewing on the web , 2011, Bioinform..

[28]  Samuel A. Smits,et al.  jsPhyloSVG: A Javascript Library for Visualizing Interactive and Vector-Based Phylogenetic Trees on the Web , 2010, PloS one.

[29]  ENCODEConsortium,et al.  An Integrated Encyclopedia of DNA Elements in the Human Genome , 2012, Nature.

[30]  K. Morris,et al.  Not so pseudo anymore: pseudogenes as therapeutic targets. , 2013, Pharmacogenomics.

[31]  A. Polański,et al.  Inter-population Differences in Retrogene Loss and Expression in Humans , 2015, PLoS Genetics.

[32]  Pedro A. F. Galante,et al.  RCPedia: a database of retrocopied genes , 2013, Bioinform..

[33]  Michael O'Shea,et al.  Evolution of nitric oxide synthase regulatory genes by DNA inversion. , 2002, Molecular biology and evolution.

[34]  Yang An,et al.  Pseudogenes regulate parental gene expression via ceRNA network , 2016, Journal of cellular and molecular medicine.

[35]  M. O'Shea,et al.  Neuronal Expression of Neural Nitric Oxide Synthase (nNOS) Protein Is Suppressed by an Antisense RNA Transcribed from an NOS Pseudogene , 1999, The Journal of Neuroscience.

[36]  M. Frith,et al.  Adaptive seeds tame genomic sequence comparison. , 2011, Genome research.

[37]  Cecilia Saccone,et al.  Pseudogenes in metazoa: origin and features. , 2004, Briefings in functional genomics & proteomics.

[38]  Izabela Makałowska,et al.  RetrogeneDB—A Database of Animal Retrogenes , 2014, Molecular biology and evolution.