11 - Repeats

• non-repetitive: unique sequences, only one copy in haploid genome

• repetitive: more than one copy:

  • moderately repetitive (complex repeats):

    • short sequences

    • 10-1000 copies

    • short interspersed repeats

  • highly repetitive (simple repeats):

    • very short (<100bp)

    • many thousands of copies

    • long tandem repeats

• Interspersed (complex)

  • Retroelements:

    • LINEs (Long Interspersed Nuclear Elements)

    • SINEs (Short “ - “)

    • LTRs (Long-terminal repeat transposons)

  • DNA-Transposons

• Tandem (simple)

  • minisatellites

  • microsatellites

  • satellite & telomeric repeats

• Segmental duplications

• can cause incorrect overlaps of fragments

• can also cause incorrect overlaps of fragments

• Microsatellites:

  • 1-12 bp, e.g., (A)*n, (CA)*n, (CGG)*n

  • formed by: replication slippage

• Minisatellites:

  • 1-500 bp

Huntington’s

• limited to well-defined chromosomal regions

  • satellites -> centromeric

  • telomeric -> end of chromosome (telomer)

• can span millions of bps

• often species-specific

3%

perfect (or slightly imperfect) tandem repeats of k-mers

~45%

• type of interspersed (complex) repeats

• can exit and re-integrate itself in genome

  • “cut-and-paste”

  • take advantage of

• ~3% of genome

• conservative: T itself moves to new location

• replicative: copy of T moves to new location

• retrotransposition: RNA copy moves to new location -> reverse transcription -> integration

• Move by retrotransposition

• e.g.

  • LTRs

  • LINEs

  • SINEs

• are retrotransposons: transcribed to RNA -> back to DNA -> integrated

• hundreds to thousands of bps

• Long interspersed nuclear elements

• autonomous retrotransposons, because

• contain own retrotransposition machinery:

  • ORF1 -> chaperone for mRNA (helps folding)

  • ORF2 -> endonuclease -> reverse transcriptase

• Short interspersed nuclear elements

• evolved from RNA genes (e.g., tRNA)

• up to 1000 bps

• nonautonomous, because

• do not have retrotranscription machinery

• Alu repeats

• ~300 bps

• > 10% of genome

• found in:

  • introns

  • 3’ UTRs of genes

  • intergenic regions

• move by conservative “cut-and-paste” mechanism

• pseudogenes commonly arise from

  • retrotransposition

• large copies of DNA (1 - >200kb) in genome

• 99% identitfy

• is everywhere in eukaryotic genomes

• evolution

• disease

• mobile elements may be coding

• they complicate alignments

• find repeats

  • k-mer approach

  • sequence self-comparison

  • periodicity approach

• build consensus of each sequence family

• classify detected sequences

• look for overrepresented k-mer

• challenge:

  • defining k (length of repeat)

  • defining number of allowed mismatches

• Repeat finding -> REPuter (1999)

  • only exact matches

• Clustering -> RepeatFinder (2001)

  • merge and extend short exact matches

• Masking -> RepeatMasker (2002)

  • uses precompiled libraries