Biology Reference
In-Depth Information
A. L1
L1 elements are members of the long interspersed element. The L1 sequence
encodes a bicistronic polymerase II (Pol-II) transcript that produces two proteins
labeled ORF1 and ORF2, both of which are necessary for successful retrotranspo-
sition. ORF1's function is poorly understood, although it has a strong affinity for
the L1 RNA sequence and is reported to exhibit nucleic acid chaperone activity
(Martin and Bushman, 2001; Martin
, 2005). The larger ORF2 protein
encodes a protein harboring both endonuclease (EN) and reverse transcriptase
(RT) activities. The protein itself has multiple functions that are conferred by the
presence of several distinct domains; these include an N-terminal EN domain
(Feng
et al.
, 1991), and a C-terminal
cysteine-rich domain of unknown function (Fanning and Singer, 1987). L1 and
the nonautonomous retroelements (such as Alu and SVA, described below)
replicate via a process known as target-primed reverse transcription (TPRT;
Cost
et al.
, 1996), a central RT domain (Mathias
et al.
, 1993), wherein reverse transcription of the RNA
intermediate is primed by an exposed 3
0
hydroxyl. The 3
0
hydroxyl strand of the
host genome is exposed as the result endonucleatic cleavage by ORF2. Based on
protein sequence analysis, the L1 lineage descends from a group of non-LTR (long
terminal repeat) elements (elements lacking long terminal repeats) that have
existed, in some form or another, since early eukaryotic evolution (Xiong and
Eickbush, 1990). It remains a matter of debate whether L1 and similar elements
were the predecessors or ancestors of modern viruses (Xiong and Eickbush, 1988).
There are approximately 500,000 L1 copies in the human genome (haploid),
comprising roughly 17% of total genome content (Lander
et al.
, 2002; Luan
et al.
, 2001). Only a
fraction of these elements are intact, full-length elements that retain the ability to
retrotranspose. Most elements are either 5
0
truncated during the insertion process,
deactivated through postinsertional mutation events, or otherwise removed from
the host population due to genetic drift and/or natural selection. There is evidence
that the majority of retrotranspositional activity actually results from a relatively
small number of particularly active, “hot,” L1 elements (Beck
et al.
et al.
, 2010; Brouha
et al.
, 2006). As is the case with the Alu, SVA, and—to a lesser
extent—HERVelements described below, moderns humans are polymorphic with
regard to the insertion status of numerous L1 inserts, making L1 an integral
component of human genetic diversity (Beck
, 2003; Seleme
et al.
et al.
, 2010; Ewing and Kazazian,
2010; Huang
et al.
, 2010; Iskow
et al.
, 2010).
B. Alu
Alu are classified as Short INterspersed Elements (SINEs). These 300 bp Pol-III
transcribed sequences are comprised of two separate domains tethered by an
A-rich linker region. Originally derived from 7SLRNA, which is a member of
