The Nature of Transposons Chapter 11 pp 300-315

Outline Nature of Transposons Transposons Prokaryotic Eukaryotic: Dr. McClintock’s research Retrotransposons vs Retroviruses

Transposons Are mobile DNA sometimes referred to as “jumping genes”.

Why are transposons in our genome? Cellular function hypothesis Antibody diversity of VDJ Genetic variation hypothesis Self-DNA hypothesis

Common features associated with transposons 1. Direct repeats Common Features Are: 2. Terminal Inverted repeats

Mechanisms of Transposition Movement through DNA intermediates Movement through RNA intermediates

DNA Transposition Movement through DNA intermediates Replicative Cut and Paste Copy and Paste Movement through DNA intermediates Replicative Non-Replicative

Non-Replicative Movement by Transposition Requires transposase 1) Transposase cuts transposon out of donor DNA (blunt cut) 2) Transposase makes a staggered cut at the target sequence 3) Transposase ligates transposon into the target 4) Gaps are filled in with DNA pol I and ligase

Direct repeats are generated Staggered cut Direct repeats are generated

Direct repeats are generated Staggered cut Direct repeats are generated

Examples of: Transposable Elements in Bacteria

1. Simple Bacterial Transposon INSERTION SEQUENCE

2. COMPOSITE TRANSPOSON IS + any DNA segment

Physiology or Medicine Dr. Barbara McClintock 1902-1992 Nobel Prize, 1983 Physiology or Medicine

“I don’t understand a word that she said, but if she says it is so, it must be so!” Alfred Sturtevant

The Ds element often results in chromosomal breakage

Drosophilia melanogaster & DNA transposition “The P Element”

The P element Codes for both Transposase Repressor of transposition

Female P- and male P+ Female P+ and male P- Offspring sterile Offspring normal Non-hybrid dysgenesis Hybrid dysgenesis Why the difference?

Remember the P element Codes for A Transposase AND A Repressor of transposition

The P element took a ride on a Science. 1991 Sep 6;253(5024):1125-8 Possible horizontal transfer of Drosophila genes by the mite Proctolaelaps regalis. Houck MA, Clark JB, Peterson KR, Kidwell MG. D. willistoni The P element took a ride on a ~50 yrs ago That moved it onto Mite D. melanogaster

Retrotransposons mRNA DNA

Examples of retrotransposons elements Yeast Ty Copia Alu Drosophila Humans

Note: retrotransposons are not found in prokaryotes General Mechanism Of Retrotransposons Note: retrotransposons are not found in prokaryotes

Types of Retrotransposons Humans Alu Non-Viral Yeast Ty Copia Viral Drosophila

Non-viral Retrotransposons Humans Non-Viral LINES SINES Example: Line 1 and Line 2 Alu

ALU 300 bp Endonuclease cutting site: site5' AG/CT 3‘ Retrotransposon 1 million in genome Linked to variety of disorders

Alu has inserted in NF-1 gene Neurofibromatosis: autosomal dominant Growth of nodules mainly affecting nerves in the skin

Viral retrotransposons look a little like retroviruses—but are NOT the same !

Now we must compare a Viral RNA with a Viral Retrotransposon

VIRAL RNA

Now a viral retrotransposon

Compare to the retrovirus Here’s the Copia element of Drosophila Similar gag and pol sequences Compare to the retrovirus

Here’s the Ty element, again notice similarities to retroviruses Delta sequences function like LTR’s in viruses

Summary Table Viral and non-viral Ty and Copia viral retrotransposons Alu non viral retrotransposons

A topic of scientific discussion is what is a “prion”?

Blunt cut from donor

HUMAN IMMUNODEFICIENCY VIRUS Human Helper T Lymphocyte