Biology Reference
In-Depth Information
Gene
Expression
a
Ancestral
Pancreas
-Actin pseudogene insertion
a
AMY2B
Pancreas
Retrovirus insertion
NTE
a
ERVA1
AMY1A
AMY1B
AMY1C
8kb
Parotid gland
3' LTR
5' LTR
Retrovirus excision
a
AMY2A
Pancreas
5' / 3' LTR
Figure 5.8.
Evolution of the human amylase genes. The insertions of the γ -actin
pseudogene (solid bar) and the retrovirus (
ERVA1
) occurred around 40 Myrs ago. Exon
a
and the untranslated exon (NTE) are represented by open boxes. An arrow denotes the
transcriptional start site (redrawn from Meisler and Ting, 1993).
described as 'perpetually mobile footprints of ancient infections' (Sverdlov, 1998)
and this mobility has sometimes been put to constructive use by evolution. For
example, the hematopoietic cell-specific expression of the human zinc finger gene
ZNF80
(3q13.3) is driven by the LTR of ERV9, a member of a low copy number
family of endogenous retroviral elements (Di Cristofano
et al
., 1995a, 1995b).
Since the ERV9 insertion was not found in the African green monkey, rhesus
macaque or orangutan, the integration of this element must have occurred after
the divergence of the orangutan from the other great apes but before the diver-
gence of the gorilla.
The LTR of a HERV-H-related sequence within an intron of a human phos-
pholipase A2-like (
Pla2l
; 8q24) gene has been shown to be important for
Pla2l
gene expression (Feuchter-Murthy
et al
., 1993; Kowalski
et al
., 1996; 1997). Since
the retroviral LTR is also present in the orthologous genes of chimpanzee and
gorilla but not in orangutan and lower primates, we may infer that it was inte-
grated into the ancestral primate genome about 15-20 Myrs ago. Upon further
analysis, it has become clear that the teratocarcinoma cell-specific
Pla2l
transcript
is actually a fusion transcript between two once distinct genes, the HERV-4-
associating 1 (
HHLA1
; 8q24) gene and the otoconin 90 (
OC90
; 8q24) gene
(Kowalski
et al
., 1999). Presumably the LTR acts not only as a strong promoter
but also as an inducer of transcriptional fusion, at least in teratocarcinoma cells
where HERV-H LTRs are known to be active transcriptionally.
A 6.3 kb endogenous retroviral element of the HERV family has been inserted
into the human pleiotrophin (
PTN
; 7q33) gene between the exons specifying the
5
untranslated region and those encoding the protein product (Schulte and
