Contractions and expansions in gene size and number - Human Gene Evolution - page 338

Since many transposable elements contain enhancer sequences, their trans-
position may have served to alter the pattern of host gene expression at or around
the integration site. Thus, once transposed, evolution may have recruited such
enhancers to play a role in the transcriptional regulation of a gene in the vicinity
of the integration site (see Chapter 5, section 5.1.12). One example of this is the
human salivary amylase ( AMY1C ; 1p21) gene where the HERV-E-derived
enhancer may be involved in tissue-specific expression (Ting et al ., 1992; Chapter
5, section 5.1.12, Endogenous retroviral elements ).
Evolution may also recruit transposable elements as a means to alter mRNA
processing. For example, a B2 (SINE) element has become inserted into the 3

untranslated region of the murine ( lifr ) gene encoding the soluble form of the
leukemia inhibitory factor receptor (LIFR; Michel et al ., 1997). Insertion of the
B2 element has, by potentiating alternative 3

mRNA processing and alternative
splicing, given rise to a truncated mRNA species (relative to the mRNA encoding
the membrane-anchored LIFR) which encodes soluble LIFR. In the rat, no such
retrotranspositional event has occurred and the soluble form of LIFR is not
found.
A very special case of the opportunistic recruitment of a transposable element
may have been that of the recombination-activating gene (RAG) transposase pos-
tulated to have been inserted into an ancestral immunoglobulin/T-cell receptor
gene soon after the divergence of jawed and jawless fishes (Chapter 9, section
9.4.2). The subsequent conversion of this transposon into a site-specific recombi-
nase may have been the critical event in allowing the vertebrates to generate the
genetic diversity so essential for the flexible adaptive response of their immune
systems.

8.4.2 LINE elements

LINE elements have assumed considerable importance in the context both of
gene pathology and gene evolution (Kazazian and Moran, 1998). They are present
in a wide range of mammals (Furano and Usdin, 1995) and are represented by
some 40 subfamilies (Smit et al ., 1995). They are nonrandomly distributed in the
human genome, inserting preferentially into chromosomal G bands (Wichman et
al ., 1992) and at the DNA level, into A-rich sequences (Vanin, 1984). The total
numbers of LINE elements in four of the great apes have been estimated by Hwu
et al . (1986): human, 107 000; chimpanzee, 51 000; gorilla, 64 000; and orangutan,
84 000. Since these figures differ markedly, it follows that numerous insertions
and deletions of these sequences must have occurred during the evolution of the
great apes.
In a pathological context, a number of examples of gene inactivation through
insertion of LINE elements into gene coding sequences are known (Miki et al .,
1992; Narita et al ., 1992; reviewed by Cooper and Krawczak, 1993) and in some
cases a preference for integration at AT-rich sequences is exhibited (Kariya et al .,
1987; Kazazian et al ., 1988). Further, the target sites of two LINE elements
inserted into the factor VIII ( F8C ; Xq28) gene causing hemophilia A (Kazazian et
al ., 1988) are 80% homologous to a 10 nucleotide motif (GAAGACATAC) present
in one of the highly favored retroviral insertion target sequences reported by Shih
et al . (1988).