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include the chicken ( Sherman et al. 1998 ) and the zebra fish ( Fadool et al. 1998 ).
It even transformed the flagellate protozoan Leishmania major , which indi-
cates that mariner has a general ability to “parasitize the eukaryotic genome”
( Gueiros-Filho and Beverley 1997 ), perhaps because host proteins are not
required for successful integration.
At least two different subfamilies of mariner were isolated from the human
genome, suggesting multiple horizontal transfers occurred, and Oosumi et al.
(1995) suggested that mariner could be used as a transformation vector for
humans. A mariner vector from fish was genetically engineered to make it more
active in humans; through genetic recombination and site-directed mutagenesis
of a mariner -like defective element, a new element called Sleeping Beauty was
constructed that had 25-fold higher levels of activity in human cells than the
“standard” mariner ( Plasterk et al. 1999 ). Sleeping Beauty is active in tissue-cul-
ture cells, as well as the germ line of the mouse and zebrafish ( Ivics et al. 2004 ).
So far, all mariner elements discovered in humans are “molecular fossils
derived from a mariner that was long ago active in the genome of a human
ancestor,” with each copy having multiple mutations ( Robertson and Martos
1997 ). Robertson and Zumpano (1997) found that mariner sequences are pres-
ent in all major primate lineages, and estimated that there are 200 copies
of one ( Hsmar1 ) in the human genome, as well as 2400 copies of a derived
80-bp inverted repeat structure and 46,000 copies of single inverted repeats,
suggesting that mariner had “a considerable mutagenic effect on past primate
genomes.” The human genome is estimated to have been invaded by at least 14
families of TEs and is estimated to have > 100,000 degenerate copies of TEs ( Smit
and Riggs 1996 ). These include elements called pogo (originally discovered in
Drosophila ) and Tigger , which are related to Tc1 and mariner ( Robertson 1996 ).
Despite the successes in transforming chickens, fish and other organisms, rates
of transformation of arthropods with mariner vectors have been low ( Lampe
et al. 2000 ). Coates et al. (1995) found mariner could excise in D. melanogas-
ter , D. mauritiana , Lucilia cuprina , and Bactrocera tryoni embryos. Wang et al.
(2000) showed that mariner could mediate excision and transposition in Bombyx
mori tissue-culture cells. Later, mariner was shown to transform Aedes aegypti
( Coates et al. 1998 ). Some mutants of the transposase gene from a mariner iso-
lated from Haematobia irritans were found to have 4- to 50-fold increases in
activity, indicating that mariner vectors could be developed that are more active
in arthropods ( Lampe et al. 1999 ). Because mariner can function in bacteria such
as Escherichia coli , it is possible to study basic biochemistry of these elements
and to improve them as genetic tools ( Lampe 2010 ).
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