Biology Reference
In-Depth Information
LINE elements are confined to the G/Q (Giemsa/Quinacrine) bands of the
euchromatin (Korenberg and Rykowski, 1988). G/Q bands are A+T rich, replicate
their DNA late during the DNA synthetic period, condense early during mitosis
and are relatively poor in expressed genes.
LINES probably represent processed pseudogene-like copies of reverse tran-
scripts which have been re-integrated into the genome (Hattori
et al
., 1986). A
full-length LINE element possesses two open-reading frames, ORF1 (1 kb) and
ORF2 (4 kb); the latter possesses reverse transcriptase activity (Mathias
et al
.,
1991) which may serve to mediate the retrotransposition not only of the LINE
elements themselves (Sassaman
et al
., 1997; DeBerardinis
et al
., 1998) but also of
other retroposons such as
Alu
sequences (Jurka 1997; Gilbert and Labuda, 1999).
LINE element transcripts have been found in undifferentiated teratocarcinoma
cells (Skowronski and Singer, 1985; Skowronski
et al
., 1988) suggesting that they
may be expressed early on in mammalian development. A promoter at the 5
end
appears to be responsible for the specific expression of LINE elements in terato-
carcinoma cells (Swergold, 1990). However, only a small subset of all LINE ele-
ments is capable of being transcribed.
Endogenous retroviral sequences and transposons.
Human transposable ele-
ments are essentially of two kinds, those that undergo transposition through a DNA
intermediate (
transposons
) and those that undergo transposition through an RNA
intermediate (
retroelements
). In excess of 10% of the human genome comprises inte-
grated copies of RNA molecules including retroviruses, retroviral-like DNAs, retro-
posons and retrotranscripts (reviewed by Cohen and Larsson, 1988; Amariglio and
Rechavi, 1993; McDonald, 1993; Leib-Mösch and Seifarth, 1996). This represents
more than 500,000 separate integration events. Nonviral retroposons include the
Alu
sequences and LINE elements discussed above. A number of endogenous retro-
viral or retroviral-like sequence families have been identified and characterized.
These include HERV-K (Ono
et al
., 1987; Goodchild
et al
., 1995; Mayer
et al
., 1997a;
1997b, 1999), RTVL-1 (Maeda and Kim, 1990), RTVL-H (Wilkinson
et al
., 1993;
Goodchild
et al
., 1993), MaLR (Smit, 1993), LTR13 (Liao
et al
., 1998), and the
immunoglobulin gene-related human transposon (THE1) (Deka
et al
., 1988; Fields
et al
., 1992; Hakim
et al
., 1994). The long terminal repeats of the HERV-K family are
capable of binding human host cell nuclear proteins (Akopov
et al
., 1998).
Retroviral sequences have sometimes become integrated into human genes (e.g.
the endogenous retrovirus HRES-1 lies within the coding sequence of the transal-
dolase gene (
TALDO
; 11p15; Banki
et al
., 1994; see Chapter 9, section 9.4) and
once transposed, they may even be recruited to play a role in the transcriptional
regulation of a gene [e.g. as postulated for the human salivary amylase (
AMY1C
)
gene (Ting
et al
., 1992); see Chapter 5, section 5.1.13].
1.1.5 Genes, mutations and disease
A central message of this volume is that the same mutational mechanisms that are
responsible for disrupting the structure and function of human genes causing
inherited disease are also responsible for having both created and fashioned these
same genes over millions of years of evolutionary time. Since Chapters 7-9 are
