Biology Reference
In-Depth Information
ing protein (
TBP
) genes are linked on chromosome 6q27 and their orthologues
are also syntenic in
Drosophila melanogaster
and
Caenorhabditis elegans
(Trachtulec,
1997). Similarly, conserved synteny is also apparent between the human genes
PIM1
,
RXRB
,
PBX2
,
NOTCH4
and
TNXA
at 6p21 and their orthologues in
D.
melanogaster
and
C. elegans
(Trachtulec, 1997). The evolutionary conservation of
close linkage over such long time periods is highly unusual and implies the exis-
tence of underlying functional reasons.
8.5.7 Functional redundancy and post-duplication diversification
Evolution is opportunistic and gene duplication provides the opportunity for
structural and functional diversification. This is well exemplified by the origin of
the
-Lactalbumin may be regarded as
essentially a mammalian 'invention'. It is a regulatory subunit of the enzyme lac-
tose synthetase. Phylogenetic analysis has indicated that
-lactalbumin gene (
LALBA
; 12q13).
-lactalbumin evolved
from lysozyme (
LY Z
; chromosome 12) (a bacteriolytic enzyme present in both
vertebrates and invertebrates) through a gene duplication event that occurred
before the divergence of mammals and birds, and prior to the evolution of the
mammary gland (Prager and Wilson 1988). The origin of the
LALBA
gene thus
appears to have long preceded the acquisition of its modern function. Its rapid
evolution in the mammalian lineage need not however have been solely due to its
acquisition of a new function. Once its lysozyme activity was lost, many of the
amino acids essential for the protein's original function were freed from selective
pressure, allowing rapid change, not all of it necessarily adaptive (Nitta and Sugai,
1989; see also discussion on function switching in Chapter 7, section 7.1.3).
The protein products of a gene duplication may sometimes be targeted to dif-
ferent cellular locations. The human mitochondrial HMG CoA synthase
(
HMGCS2
; 1p12-p13) gene encodes an enzyme which catalyses the first reaction
of ketogenesis whilst the cytoplasmic form of the enzyme, encoded by the
HMGCS1
gene (5p13), catalyses the second step in cholesterol biosynthesis from
acetyl CoA. The two genes are thought to have arisen from a gene duplication
~500 Myrs ago (Boukaftane
et al
., 1994). The emergence of the two enzymes as
distinct entities served to link the pathways of
-oxidation and leucine catabolism
and created the HMG CoA pathway of ketogenesis thereby providing a lipid-
derived energy source.
Gene duplication has also potentiated the emergence of
isozymes
, enzymes that
catalyze the same biochemical reaction but which may differ from each other in
terms of tissue specificity, developmental regulation or biochemical properties.
Thus, in vertebrates, the two subunits of lactate dehydrogenase are encoded by
two genes (
LDHA
; 11p14-p15 and
LDHB
; 12p12) and these subunits can be com-
bined in such a way as to form five tetrameric isozymes (A
4
, A
3
B, A
2
B
2
, AB
3
, and
B
4
) each with its own distinctive properties.
Iwabe
et al
. (1996) examined gene duplications during organismal evolution
and concluded that most gene duplications giving rise to entirely novel functions
predated the divergence of the vertebrate and arthropod lineages. Genes which
encode proteins that are localized to cell compartments (compartmentalized iso-
forms) emerged by duplications which predated the separation of animals and
fungi. By contrast, genes encoding products with virtually identical functions but
