oddgenes
A list of weird gene annotations or things that break bioinformatics assumptions
Gene structures
1bp length exon
Evidence given for a 1bp length exon in Arabadopsis and different splicing models are discussed
http://www.nature.com/articles/srep18087
Another 1bp exon is discussed here https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0177959
0bp length exon
The phenomenon of recursive splicing can remove sequences progressively inside an intron, so there can exist "0bp exons" that are just the splice-site sequences pasted together.
"To identify potential zero nucleotide exon-type ratchet points, we parsed the RNA-Seq alignments to identify novel splice junctions where the reads mapped to an annotated 5' splice site and an unannotated 3' splice site, and the genomic sequence at the 3' splice site junction was AG/GT"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529404/
Twintron
A twintron is essentially an intron-within-an-intron, which could be formed by a mobile element (TE) insertion. The original idea is that the internal intron has to be spliced first before the outer one is, but several classes have been discovered. See https://en.wikipedia.org/wiki/Twintron
Very large introns
Satellite DNA study uncovers megabase scale introns https://www.biorxiv.org/content/early/2018/12/11/493254
Example in human include Dystrophin spanning 2.3 million bp Example in paper kl-3 spans 4.3 million bp
Very large number of isoforms in Dscam
"Dscam has 24 exons; exon 4 has 12 variants, exon 6 has 48 variants, exon 9 has 33 variants, and exon 17 has two variants. The combination of exons 4, 6, and 9 leads to 19,008 possible isoforms with different extracellular domains (due to differences in Ig2, Ig3 and Ig4). With two different transmembrane domains from exon 17, the total possible protein products could reach 38,016 isoforms"
Ref https://en.wikipedia.org/wiki/DSCAM https://www.wikigenes.org/e/gene/e/35652.html
Translational frameshift
"The main distinction between frameshifts resulting from mutation and those resulting from ribosomal frameshifting is that the latter are controlled by various mechanisms found in codons...Certain codons take longer to translate, because there are not equal amounts of tRNA of that particular codon in the cytosol..." which leads to ribosomal slippage into an alternative reading frame
Ref https://en.wikipedia.org/wiki/Translational_frameshift
A Stop codon that is not a stop codon
In some cases a stop codon is not interpreted as such. When it is interpreted, it is sometimes called "Stop codon readthrough" and can encode for an amino acid. The amino acid Selenocysteine is coded for by a stop codon (https://en.wikipedia.org/wiki/Selenocysteine) and Pyrrolysine also is coded for by a stop codon (https://en.wikipedia.org/wiki/Pyrrolysine). Both of these lie outside the conventional 20 amino acid code
There are several other stop codon modifications described here http://www.nature.com/nrg/journal/v16/n9/box/nrg3963_BX2.html?foxtrotcallback=true
From a gene annotation perspective, there are also other nasty "stop codon readthrough" usages due to genome misassembly, but we will pretend all our genomes come from heaven in perfect xerox form.
Non-canonical splice sites
The standard splice site recognition sequence is an GU in RNA (or GT in DNA) on the 5' end and AG on the 3' (remember, goes 5' to 3'). This recognition motif accounts for the large majority of splicing. If a different sequence is used it is said that a different spliceosome complex is being used "minor spliceosome"
https://en.wikipedia.org/wiki/Minor_spliceosome
Cryptic splice sites
Some exons harbor internal splice sites (e.g. they get split) that might be unused or underused and are so called "cryptic splice sites"
Review article https://academic.oup.com/nar/article/39/14/5837/1382796
The snaptron project from Ben Langmead analyzed huge amounts of RNA-seq public data and found many types of these cryptic splicing http://snaptron.cs.jhu.edu/
Intron retention
Intron retention is a phenomenon where intron sequence is preserved in mature RNA
It can occur in both abnormal and normal biological conditions. Transcript with IR often undergo nonsense-mediated decay.
Introns in archaea
The only types of introns known conventionally in archaea are called "bulge-helix-bulge" but recently Group 1 introns have been discovered https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gky414/4999243
Self-splicing RNA
The Group 1 intron type mentioned above is a "self splicing" function of RNA not requiring external spliceosome https://en.wikipedia.org/wiki/Group_I_catalytic_intron
Group 2 and group 3 with similar but different mechanisms also exist
Codon tables
Many eukaryotes use the "standard genetic code" for changing codons to amino acids but frequent changes occur across the domains of life. The NCBI "genetic code" table lists several of these and contains recent additions for particular species
https://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi#SG31
One article explains how alternative genetic codes work https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207430/
Untranslated regions
The 5' and 3' UTR (un-translated region) is a part of the pre-mRNA at the start and end of the gene respectively that is spliced away in the mature RNA
This blog post by Ensembl shows how they annotate UTR and 19kb 3' UTR in Grin2b http://www.ensembl.info/2018/08/17/ensembl-insights-how-are-utrs-annotated/
They have many important functionality and are often targets of miRNA binding which leads to degradation.
Poly-A tails
A poly-A tail is added to the pre-mRNA on the 3' end of the transcript to protect it from degradation. The A signal is not part of the genome https://en.wikipedia.org/wiki/Polyadenylation
A survey of poly-A using Oxford Nanopore found some transcript isoforms with 450bp ENST00000581230, with intron retention being a possible correlate of having a longer poly-A tails https://www.biorxiv.org/content/early/2018/11/09/459529.article-info
Intronic polyadenylation can also occur https://www.nature.com/articles/s41467-018-04112-z it is revealed by 3'-seq
Circular chromosomes
Circularized chromosomes should be unsurprising to anyone working with plasmids but for gene annotation formats which use linear coordinates, representing anything wrapping around the origin is challenging
Many genomic viewers do not do this well. For GFF format this is done by making the end go past the end of the genome. Below, the genome is 6407 bp in length, but the CDS feature extends past this and sets Is_circular=true
##gff-version 3.2.1
# organism Enterobacteria phage f1
# Note Bacteriophage f1, complete genome.
J02448 GenBank region 1 6407 . + . ID=J02448;Name=J02448;Is_circular=true;
J02448 GenBank CDS 6006 7238 . + 0 ID=geneII;Name=II;Note=protein II;
Flybase
Chimeric genes
The gene Jingwei is a chimera of two genes, alcohol dehydrogenage and yellow emperor. Many chimeras are damaging but this has been selected for
http://www.pnas.org/content/101/46/16246
Wormbase
Adding leader sequence to mRNA
"About 70% of C. elegans mRNAs are trans-spliced to one of two 22 nucleotide spliced leaders. SL1 is used to trim off the 5' ends of pre-mRNAs and replace them with the SL1 sequence. This processing event is very closely related to cis-splicing, or intron removal."
The region that is spliced out is called an outron
http://www.wormbook.org/chapters/www_transsplicingoperons/transsplicingoperons.html
Polycistronic transcripts/operons
Although prevalent in bacteria, operons are not common in eukaryotes. However, they are common in C. elegans specifically. "A characteristic feature of the worm genome is the existence of genes organized into operons. These polycistronic gene clusters contain two or more closely spaced genes, which are oriented in a head to tail direction. They are transcribed as a single polycistronic mRNA and separated into individual mRNAs by the process of trans-splicing"
http://www.wormbook.org/chapters/www_overviewgenestructure.2/genestructure.html
Trans-splicing of exons on different strands
A pre-mRNA from both strands of DNA eri6 and eri7 are combined to create eri-6/7
Source http://forums.wormbase.org/index.php?topic=1225.0 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756026/
Exon shared across different genes
An example from drosophila, C. elegans, and rat shows a gene with a 5' exon being shared between two genes
Source http://forums.wormbase.org/index.php?topic=1225.0 https://www.fasebj.org/doi/full/10.1096/fj.00-0313rev
Evolution
Possible adaptive bacteria->eukaryote HGT
A possible horizontal gene transfer from bacteria to eukaryotes is found in an insect that feeds on coffee beans. Changes that the gene had to undergo are covered (added poly-A tail, shine-dalgarno sequence deleted)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306691/
Transgenerational epigenetic inheritence
This phenomena of epigenetic modifications being passed down across generations garners a lot of media attention and scientific attention. The idea of it being influenced by what "one does in life" such as experiencing famine is also very interesting.
https://en.wikipedia.org/wiki/Transgenerational_epigenetic_inheritance
There are skeptics also http://www.wiringthebrain.com/2018/07/calibrating-scientific-skepticism-wider.html but the science is hopefully what speaks for itself
Codon usage
Alternative start codons
"The most common start codons for known Escherichia coli genes are AUG (83% of genes), GUG (14%) and UUG (3%)"
"Here, we systematically quantified translation initiation of green fluorescent protein (GFP) from all 64 codons and nanoluciferase from 12 codons on plasmids designed to interrogate a range of translation initiation conditions."
https://www.sciencedaily.com/releases/2017/02/170221080506.htm
Molecular
Complex DNA structures
The standard DNA double stranded helix is called B-DNA (https://genome.cshlp.org/content/early/2018/11/06/gr.241257.118.abstract)
Other geometries are possible https://en.wikipedia.org/wiki/Nucleic_acid_double_helix#Helix_geometries
Complex structures such as four stranded quadruplex have been found that could have biological functions
See https://news.cnrs.fr/articles/unlocking-the-secrets-of-four-strand-dna
RNA world
RNA modifications
https://www.hindawi.com/journals/jna/2011/408053/tab1/
updated link on hindawi should point here http://mods.rna.albany.edu/mods/
RNA editing
RNA editing is a post-transcriptional modification to the mRNA to change the bases. A-to-I editing is a common one in mammals which would make the RNA appear to have a G where there is an A is in the genomic DNA.
Other editing occurs also https://en.wikipedia.org/wiki/RNA_editing
Maternal RNAs being passed down
Maternal RNAs being active against the zygote (e.g. https://en.wikipedia.org/wiki/Maternal_to_zygotic_transition) and lead to complex transgenerational effects
Lowly expressed RNA has large effects
A lncRNA VELUCT almost flies under the radar in a lung cancer screen due to being very lowly expressed such that it is "below the detection limit in total RNA from NCI-H460 cells by RT-qPCR as well as RNA-Seq", however this study confirms it as a factor in experiments
https://www.ncbi.nlm.nih.gov/pubmed/28160600?dopt=Abstract
X chromosome inactivation
X chromosome inactivation is produced by a non-coding transcript called Xist is transcribed on the X that is being inactivated and actually coats the X chromosome with itself. An anti-sense transcript called Tsix regulates Xist
https://en.wikipedia.org/wiki/XIST
Transposons
Cross-species BovB transposon transfers
Or "How a quarter of the cow genome came from snakes" http://phenomena.nationalgeographic.com/2013/01/01/how-a-quarter-of-the-cow-genome-came-from-snakes/
Source http://www.pnas.org/content/110/3/1012.full
LINE1 important for embryonic development
Transposon activity can mutate DNA as it will insert itself into the genome. The genome has functions for keeping transposons inactive. However, evidence shows that the LINE1 is important for embryonic development.
https://www.ucsf.edu/news/2018/06/410781/not-junk-jumping-gene-critical-early-embryo
Immunity
VDJ Recombination
VDJ recombination is a process of somatic recombination (using "recombination signal sequences") that is done in immune cells. Different gene segments of class "V", class "D", and class "J" exons (sometimes to exons are referred to as "genes" themselves) are somatically rearranged into coherent genes that are then transcribed and immune diversity.
https://en.wikipedia.org/wiki/V(D)J_recombination
Pseudogenes
A pseudogene that can protect against cancer in Elephants
The LIF gene has many copies in Elephant but many are non-functional. One copy can be "turned back on" and play a role in cancer protection. They call this a "zombie gene"
https://www.cell.com/cell-reports/fulltext/S2211-1247(18)31145-8
https://www.sciencealert.com/lif6-pseudogene-elephant-tumour-suppression-solution-petos-paradox
Regulation
Intron mediated enhancement (IME)
It has been shown that some intron sequences can enhance expression similar to how promoter sequences work https://en.wikipedia.org/wiki/Intron-mediated_enhancement
The first intron of the UBQ10 gene in Arabidopsis exhibits IME, and "the sequences responsible for increasing mRNA accumulation are redundant and dispersed throughout the UBQ10 intron" http://www.plantcell.org/content/early/2017/04/03/tpc.17.00020.full.pdf+html
Bidirectional promoters
Wikipedia https://en.wikipedia.org/wiki/Promoter_(genetics)#Bidirectional_(mammalian)
"Bidirectional promoters are a common feature of mammalian genomes. About 11% of human genes are bidirectionally paired."
"The two genes are often functionally related, and modification of their shared promoter region allows them to be co-regulated and thus co-expressed"
File formats
Non-ACGT letters in fasta files
The latest human genome, for example, downloaded from NCBI, contains a number of Non-ACGT letters in the form of IUPAC codes https://www.bioinformatics.org/sms/iupac.html These represent ambiguous bases.
Here is the incidence of non-ACGT IUPAC letters in the entire human genome GRCh38.p10 NC_000001-24
b: 2
k: 8
m: 8
r: 26
s: 5
w: 14
y: 35
Did you expect that in your bioinformatics software? Note that the mouse genome (GRCm38.p5) as far as I could tell does not contain any non-ACGT IUPAC letters
rs SNP identifiers occuring in multiple places
Due to how dbSNP is creating, an rs SNP ID can occur in multiple places on the genome https://www.biostars.org/p/2323/
Weird characters in FASTA sequence names
In response to hg38 including a colon in sequence names, which conflicts with commonly used representation of a range as chr1:1-100 for example, people analyzed meta-character frequencies in sequence names samtools/hts-specs#291
ENA
# 16927
* 1
, 231
- 122563947
. 521540419
/ 236951
\ 0
: 30181
; 72892
= 186611
@ 3713
| 949
Broad(?)
12 #
527 *
357 ,
1451132 -
1492749 .
86114 /
233731 :
2034 =
17 @
1735713 |
Reference sequences
# 203
% 203
* 525
+ 1
, 496
- 154226
. 1826561
: 1577
= 26
_ 4961932
| 1098333
Note that commas in FASTA names is being suggested as an illegal character because of the supplementary alignment tag in SAM/BAM using comma separated values
Interesting gene names
- Tinman - https://en.wikipedia.org/wiki/Tinman_gene
- Sonic hedgehog (SHH) - https://en.wikipedia.org/wiki/Sonic_hedgehog
- Heart of glass (heg) - https://www.ncbi.nlm.nih.gov/pubmed/14680629
- Dracula (drc) - https://www.ncbi.nlm.nih.gov/pubmed/10985389
- Sleeping Beauty transposon - https://en.wikipedia.org/wiki/Sleeping_Beauty_transposon_system
- Skywalker protein - http://www.ebi.ac.uk/pdbe/entry/search/index?pubmed_id:27669036
- Time for coffee - http://www.plantcell.org/content/15/11/2719.abstract
- Wtf4 - https://www.sciencedaily.com/releases/2017/06/170620093209.htm
- Mothers against decapentaplegic - https://en.wikipedia.org/wiki/Mothers_against_decapentaplegic
- Saxophone (sax) - http://www.sdbonline.org/sites/fly/gene/saxophon.htm
- Beethovan (btv) - http://www.uniprot.org/uniprot/Q0E8P6
- Superman+kryptonite - https://en.wikipedia.org/wiki/Superman_(gene)
- Supervillin (SVIL) - https://www.uniprot.org/uniprot/O95425
- Wishful thinking (wit) - https://www.wikigenes.org/e/gene/e/44096.html
- Doublesex (dsx) - https://en.wikipedia.org/wiki/Doublesex
- Fruitless (fru) - https://en.wikipedia.org/wiki/Fruitless_(gene)
- Transformer (tra) - https://en.wikipedia.org/wiki/Transformer_(gene)
- Gypsy+Flamenco - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1206375/
- Jockey - http://flybase.org/reports/FBgn0015952.html
- Tigger - https://www.omim.org/entry/612972
- Nanog - celtic legend https://www.sciencedaily.com/releases/2003/06/030602024530.htm (source https://twitter.com/EpgntxEinstein/status/1057359656220348417)
- Jerky (jrk) - https://www.genecards.org/cgi-bin/carddisp.pl?gene=JRK
- Hippo (Hpo) - https://www.wikigenes.org/e/gene/e/37247.html
Great illustrations of interesting biology, including information about gene names https://twitter.com/vividbiology
Many of the stories behind fly gene nomenclature is available at https://web.archive.org/web/20110716201703/http://www.flynome.com/cgi-bin/search?source=browse including the famous ForRentApartments dot com gene (just kidding but lol https://web.archive.org/web/20110716202150/http://www.flynome.com/cgi-bin/search?storyID=180)
Musing article: "What is in a (gene) name?" https://blogs.plos.org/toothandclaw/2012/06/17/whats-in-a-gene-name/
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