a unified classification system for eukaryotic transposable elements wicker et al sarah mangum

A unified classification system for eukaryotic transposable elements Wicker et al

Sarah Mangum

Class I mobilization (‘copy and paste’)

Pol III transcription

Reverse transcription and insertion

1. Usually a single or a few ‘master’ copy(ies)

2. Transcription to an RNA intermediate (copy)

3. Placed back into another location in the genome (paste)

Two Classes: Class I (Retrotransposons) and Class II (DNA Transposons)

DNA Transposons• Double strand break in donor DNA

• Helitrons and Mavericks undergo ‘copy and paste’ mobilization however have no RNA intermediate.

Class II mobilization (‘cut and paste’)

Transposon w/ ORF

Pol II transcription

Transposase

Translation

Donor

Target

Target Site Duplications (TSDs)

Upon insertion, small direct repeats are created flanking the element.

ClassificationClass -- divided by presence of RNA intermediateSubclass -- distinguish between ‘copy and paste’ and ‘cut and paste’ Order -- differences in insertion mechanisms and organizationSuperfamily -- differences in protein structure and non-coding domains

and TSDsFamily -- DNA sequence similaritySubfamily -- phylogenetic; autonomous and non-autonomous derivatives

Insertion -- individual copy after insertion event

*All classification names below order should be italicized.

Long Terminal Repeat (LTR) Retrotransposon

• High presence in plants

• LTRs flanking element = 300- 5kb; start with 5’-TG-3’ and end with 5’-CA-3’• Produce 4-6 bp TSD• Usually code for GAG and POL

• POL contains aspartic proteinase (AP), reverse transcriptase (RT), RNase H (RH), and DDE intergrase (INT)

• Gypsy and Copia differ in order of RT and INT

• Also within the LTR order are retroviruses and endogenous retroviruses (ERVs)

• Retroviruses may have evolved from LTRs or vice versa • Retroviruses contain an envelope protein (ENV) as well as other

additional proteins different from the LTR • ERVs are retroviruses whose domains were either inactivated or

deletion of domains necessary for extracellular mobility• ERVs also encode for capsid and matrix functions as well as ENV

Long Terminal Repeat (LTR) Retrotransposon

LTR transposition

Solo LTR – easy to lose internal region of LTR transposon during replication.

Class I (con’t)• DIRS-like element:

• Contain tyrosine recombinase instead of INT thus, no TSDs• Termini contain split direct repeats (SDR) or inverted repeats

• Penelope-like (PLE) element:• Detected in over 50 species but variable distribution among taxa• RT similar to telomerase• Some contain functional introns• LTR-like flanking sequences direct or inverse

Long Interspersed Elements (LINEs)• Can reach several kb in length • Autonomous• Encode RT and nuclease in pol• R2: nuclease = endonuclease in C-terminal of RT• L1, RTE, I, Jockey: nuclease = endonuclease in

N-terminal of RT• Usually forms TSD upon insertion• Weak RT falls off leaving many truncated LINEs• 3’ end contains either a poly(A) tail, tandem repeat

or A-rich region

Short Interspersed Elements (SINEs)• Non-autonomous• Use LINE machinery

• Some have obligatory partners, other are generalists

• Not autonomous derivative• Originate from accidental retrotransposition of polymerase III

transcripts (tRNA, 7SL RNA, and 5S RNA)• 5’: RNA Polymerase III transcription start site; often derived from tRNA• 3’: usually LINE derivative; can contain poly(T) tail, A or AT rich, or 3-5 bp

tandem repeat• 80 – 500 bp long TSD: 5-15 bp

Class II Elements

• Subclass I (cut and paste)• DNA Transposons

• Subclass II (copy and paste)• Helitrons • Mavericks

DNA Transposons (TIRs)• Distinguished by terminal inverted repeats (TIRs) and TSD size• Can increase numbers by transposing during chromosome replication• Use transposase for transposition• Tc1-Mariner: two TIRs and transposase ORF; usually TA TSD• hAT: TSDs of 8bp; TIRs of 5-27 bp; overall length of less than 4kb• Mutator: TIRs can reach several hundred bp; 9-11 bp TSDs• P element: 8 bp TSDs • piggyBac: 8 bp TSDs usually TTAA • PIF-Harbinger: TSD: TAA• CACTA: 3-bp TSDs

Helitron• Replication without double stranded (ds) cleavage• Replicate via rolling circle mechanism with no TSDs• Short hairpin structure defines the end 3’ end along

with TC or CTRR motifs • Encode tyrosine recombinase

Damon Lisch Nature Reviews Genetics 14, 49-61 (January 2013)

Mavericks• Also called Polinton• Replication without ds

cleavage• Large! • 10-20 kb • Long TIRs border• Encode DNA pol B and

INT • No RT

Kapitonov V V , and Jurka J PNAS 2006;103:4540-4545

Autonomous vs Non-Autonomous Classification

• Autonomous: encode all domains necessary for transposition

• Defective code is still classified autonomous

• Non-Autonomous: containing no or not all of the domains necessary for transposition

Non-AutonomousDerived from LTRs: • Large retrotransposon derivatives (LARDs)

• Large; greater than 4 kb; no coding region for transposition

• Terminal repeat retrotransposons in miniature (TRIMs)• Small; less than 4 kb; no coding region for transposition

Miniature inverted repeat transposable elements (MITEs):• Flanked by TIRs; often found close to genes

Naming system• A three-letter code:

• Letters denote class, order, and lastly superfamily

• Family name, separated by an underscore • Sequence ID of element location

RLC_Angela_AA123456-1R = RNA (Class I)L = LTRC = Copia

Families• Defined by:

• similarities in sequence in: • coding region (or internal domain)• Terminal repeats

• 80-80-80 rule:• 80% sequence similarity over 80% of the

sequence and over 80 base pairs long• Can apply to internal region or terminal

repeat region or both

Questions?

Emiliani G, Paffetti D, Giannini R. 2008. Identification and molecular characterization of LTR and LINE retrotransposable elements in Fagus sylvatica L.