Contractions and expansions in gene size and number - Human Gene Evolution - page 336

that undergo transposition through a DNA intermediate, and those that undergo
transposition through an RNA intermediate. Transposable elements with a DNA
intermediate are termed transposons and these are characterized by terminal
inverted repeats and duplication of the target site (visible as direct repeats flank-
ing the element). However, the great majority of transposable elements in the
human genome have undergone retrotransposition through an RNA intermedi-
ate. Such retroelements or retroposons may be of either viral or nonviral origin ( Table
8.1 ). Whilst endogenous retroviral sequences comprise some 0.1-0.6% of the
human genome (Leib-Mösch et al ., 1990), the nonviral Alu sequences and LINE
elements may together make up as much as 10% of the genome.
8.4.1 Endogenous retroviral sequences and transposable elements
Retroposons. A number of retroposon families have been characterized in pri-
mate genomes (Leib-Mösch and Seifarth, 1996; McDonald, 1993; Table 8.1 ).
Occasionally, these are human-specific (e.g. the HERV-K10-related SINE-R.C2;
Zhu et al. , 1992; 1994) but usually they are found distributed through the
genomes of other primate species (e.g. RTVL-H (Goodchild et al. , 1993), RTVL-I
(Maeda and Kim, 1990), HERV-K (Steinhuber et al. , 1995), and HERV-L
(Cordonnier et al. , 1995)). Type I and II HERV-H elements were amplified to
~1000 copies after the divergence of New World from Old World monkeys but
before the divergence of apes from Old World monkeys (Leib-Mösch and
Seifarth, 1996). By contrast, the family of type Ia HERV-H elements expanded to
~100 copies only after the divergence of apes from Old World monkeys. Analysis
of the copy number, distribution and sequence characteristics of such endogenous
elements promises to provide important clues as to the evolutionary history and
phylogeny of the various mammalian orders, suborders, and species, and even the
population genetics of human racial groups (Furano and Usdin, 1995).
Retroposons have sometimes become integrated into the vicinity of human
genes. Thus, two copies of an RTV L -I sequence are present in the human haptoglo-
bin ( HP ; 16q22.1) gene cluster whilst an additional copy has been inserted in the
same region in the orthologous chimpanzee gene (Maeda and Kim, 1990). Rather
more dramatically, the endogenous retrovirus, HRES-1 lies within the coding
sequence of the human transaldolase gene ( TALDO1 ; 11p15; Banki et al ., 1994).
One view of endogenous retroviral elements is that they inserted themselves
into the germline of our primate ancestors during the last 40 Myrs as a result of
infection with exogenous retroviruses, persisting thereafter as proviruses, albeit
rendered replication-defective by multiple mutational events (Shih et al ., 1991).
Another (not incompatible) view is that retroviruses themselves originally arose
from intracellular retroelements (the protovirus hypothesis), a view which is sup-
ported by the phylogenetic analysis of endogenous retroviral DNA sequences
( Figure 8.4 ). Regardless of whether or not the horizontal transmission of retrovi-
ral elements has taken place, copy number amplification has certainly occurred.
Retrotransposition often generates retroposon sequence variants owing to its
inherent imprecision: target site rearrangements combine with the infidelity of
both reverse transcriptases and RNA-dependent RNA polymerases to ensure that
the inserted sequences are highly variable thus providing new avenues for the
highly opportunistic evolutionary process (Preston, 1996).