Description
Retrotransposition is a process involving the copying of DNA by a group of
enzymes that have the ability to reverse transcribe spliced mRNAs, resulting
in single-exon copies of genes and sometime chimeric genes. RetroGenes can be
either functional genes that have acquired a promoter from a neighboring gene,
non-functional pseudogenes, or transcribed pseudogenes.
Methods
All mRNAs of a species from GenBank were aligned to the genome using
lastz
(Miller lab, Pennsylvania State University). mRNAs that aligned twice in the genome
(once with introns and once without introns) were initially screened. Next, a series
of features were scored to determine candidates for retrotransposition events. These
features included position and length of the polyA tail, degree of synteny with human,
coverage of repetitive elements, number of exons that can still be aligned to the
retrogene and degree of divergence from the parent gene. Retrogenes were classified
using a threshold score function that is a linear combination of this set of features.
Retrogenes in the final set were selected using a score threshold based on a ROC plot
against the Vega annotated
pseudogenes.
Retrogene Statistics table:
- Expression of Retrogene: The following values are possible where
those that are not expressed are classed as pseudogene or
mrna:
- pseudogene indicates that the parent gene has been annotated
by one of NCBI's RefSeq, UCSC Genes or Mammalian Gene Collection (MGC).
- mrna indicates that the parent gene is a spliced mrna that
has no annotation in NCBI's RefSeq, UCSC Genes or Mammalian Gene Collection
(MGC). Therefore, the retrogene is a product of a potentially non-annotated
parent gene and is a putative pseudogene of that putative parent gene.
- expressed weak indicates that there is a mRNA overlapping
the retrogene, indicating possible transcription. noOrf indicates
that an ORF was not identified by BESTORF.
- expressed indicates that there is a medium level of mRNAs/ESTs
mapping to the retrogene locus, indicating possible transcription.
- expressed strong indicates that there is a mRNA overlapping
the retrogene, and at least five spliced ESTs indicating probable transcription.
noOrf indicates that an ORF was not identified by BESTORF.
- expressed shuffle indicates that the retrogene was inserted into
a pre-existing annotated gene.
- Score: Based on features of the potential retrogene.
- Percent Gene Alignment Coverage (Bases Matching Parent): Shows
the percentage of the parent gene aligning to this region.
- Intron Count: Number of introns is the number of gaps in
the alignment between the parent mRNA and the genome where gaps are >80 bp and
the ratio of the mRNA alignment gap to the genome alignment gap is less than
30% after removing repeats.
- Gap Count: Numer of gaps in the alignment of between the parent
mRNA and the genome after removing repeats. Gaps are not counted if the gap on
the mRNA side of the alignment is a similar size to the gap in the genome
alignment.
- BESTORF Score:
BESTORF (written by Victor Solovyev) predicts potential open reading
frames (ORFs) in mRNAs/ESTs with very high accuracy using a Markov chain model of coding
regions and a probabilistic model of translation start codon potential. The score
threshold for finding an ORF is 50 (Jim Kent, personal communication).
Break in Orthology table:
Retrogenes inserted into the genome since the mouse/human divergence show a break
in the human genome syntenic net alignments to the mouse genome. The percentage
break represents the portion of the genome that is missing in each species relative
to the reference genome (mouse mm10) at the retrogene locus as defined by syntenic
alignment nets. Breaks in orthology with human and dog tend to be due to genomic
insertions in the rodent lineage. Relative orthology of human/mouse and dog/mouse
nets are used to avoid false positives due to deletions in the human genome. Older
retrogenes will not show a break in orthology, so this feature is weighted lower than
other features when scoring putative retrogenes.
These features can be downloaded from the table retroMrnaInfo in many formats using
the Table Browser option from the Tools menu in the top blue navigation bar.
Credits
The RetroFinder program and browser track were developed by
Robert Baertsch at UCSC.
References
Baertsch R, Diekhans M, Kent WJ, Haussler D, Brosius J.
Retrocopy contributions to the evolution of the human genome.
BMC Genomics. 2008 Oct 8;9:466.
PMID: 18842134; PMC: PMC2584115
Kent WJ, Baertsch R, Hinrichs A, Miller W, Haussler D.
Evolution's cauldron: duplication, deletion, and rearrangement in the mouse and human genomes.
Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11484-9.
PMID: 14500911; PMC: PMC208784
Pei B, Sisu C, Frankish A, Howald C, Habegger L, Mu XJ, Harte R, Balasubramanian S, Tanzer A,
Diekhans M et al.
The GENCODE pseudogene resource.
Genome Biol. 2012 Sep 26;13(9):R51.
PMID: 22951037; PMC: PMC3491395
Schwartz S, Kent WJ, Smit A, Zhang Z, Baertsch R, Hardison RC, Haussler D, Miller W.
Human-mouse alignments with BLASTZ.
Genome Res. 2003 Jan;13(1):103-7.
PMID: 12529312; PMC: PMC430961
Zheng D, Frankish A, Baertsch R, Kapranov P, Reymond A, Choo SW, Lu Y, Denoeud F, Antonarakis SE,
Snyder M et al.
Pseudogenes in the ENCODE regions: consensus annotation, analysis of transcription, and
evolution.
Genome Res. 2007 Jun;17(6):839-51.
PMID: 17568002; PMC: PMC1891343
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