Biology Reference
In-Depth Information
witness at mutation the birth of a new gene or at least its activation. The num-
ber of active genes in the world has been increased by one.
T.H. Morgan (1926)
The Theory of the Gene
During the evolution of the mammalian genome, new genes have often emerged
by duplication and divergence (Chapter 4 and Section 9.5). Another, albeit less
common route has been via retrotransposition (Brosius, 1991; Nouvel, 1994). At
least five functional human genes have a structure consistent with their having
arisen by retrotransposition: the phosphoglycerate kinase 2 (
PGK2
; 19) gene
(Boer
et al
., 1987; McCarrey and Thomas, 1987; McCarrey, 1990), the pyruvate
dehydrogenase
2 (
PDHA2
; 4q22-q23) gene (Dahl
et al
., 1990), the cAMP-depen-
dent protein kinase C
subunit (
PRKACG
; 9q13) gene (Reinton
et al
., 1998), the
SR splicing factor SRp46 (
Srp46
; 11q22; Soret
et al
., 1998) gene and the Y-encoded
zinc finger protein (
ZFY
: Yp11.3) gene (Ashworth
et al
., 1990). All are character-
ized by a lack of introns and a chromosomal location different and distinct from
their presumed parent genes (
PGK1
, Xq13;
PDHA1
, Xp22.1-p22.2;
PRKACA
,
19p13.1;
ZFX
, Xp21.3-p22.2 respectively). In the case of the
PRKACG
gene,
there are also remnants of flanking direct repeats and a poly(A) tail providing fur-
ther evidence of the retrotranspositional origin of the gene (Reinton
et al
., 1998).
This type of sequence has sometimes been referred to as a 'functional retro-
pseudogene' but this is surely a misnomer. Functional it may be, but pseudogene
it is not, and so a better term would be 'retrotransposed gene'.
The retrotransposed
PGK2
gene originated prior to the divergence of eutherian
and metatherian mammals some 125 Myrs ago and has been characterized in
some detail (McCarrey, 1990). It is expressed only in spermatogenic cells whereas
its putative parent (
PGK1
) is ubiquitously expressed. Sequence comparison stud-
ies are consistent with the newly retrotransposed
PGK2
gene having possessed
regulatory sequences derived from the
PGK1
gene which facilitated the initial
expression of the intronless gene. Inclusion of promoter sequence could have
come about if the
PGK1
-derived
PGK2
mRNA intermediate had initiated aber-
rantly at an upstream start site as McCarrey (1990) suggested, or instead from an
alternative upstream promoter. This promoter sequence might then be envisaged
to have evolved cell type specificity, a process presumably involving loss of the
CpG island still apparent in the
PGK1
gene. Interestingly, the
PDHA2
and
PRKACG
genes are also expressed exclusively in the spermatogenic cells of the
testis. In the case of the X-linked
PGK1
and
PDHA1
genes, transposition to an
autosome might have been selectively advantageous in that it would have ensured
expression of these important enzyme encoding genes in Y-bearing as well as X-
bearing spermatozoa.
References
Agrawal A., Eastman Q.M., Schatz D.G.
(1998) Transposition mediated by RAG1 and RAG2 and its
implications for the evolution of the immune system.
Nature
394
: 744-751.
Amann J., Valentine M., Kidd V.J., Lahti J.M.
(1996) Localization of
Chl
1-related helicase genes to
human chromosome regions 12p11 and 12p13: similarity between parts of these genes and
conserved human telomeric-associated DNA.
Genomics
32
: 260-265.
