Biology Reference
In-Depth Information
family members in the human genome: the insulin (
INS
), insulin-like growth
factor 2 (
IGF2
) and Harvey RAS (
HRAS
) genes are located on chromosome 11p
whilst the insulin-like growth factor 1 (
IGF1
) and Kirsten RAS (
KRAS2
) genes
are located on chromosome 12 (Hoppener
et al
., 1985).
That the genome duplications occurred prior to the adaptive radiation of the
vertebrates is evidenced by the similar gene number exhibited by both fish and
mammals (Elgar
et al
., 1996), the survival of syntenic linkage groups over quite
long periods of evolutionary time (Lundin 1993; Trower
et al
., 1996) and the
tetralogy exhibited by many vertebrate loci. This tetralogy is evident from the
observation that the basic set of ~15 000 genes found in all primitive metazoans
varies only moderately from
Caenorhabditis elegans
(Ahringer, 1997) to
Drosophila
(Miklos and Rubin, 1996) to
Ciona intestinalis
, a tunicate (Simmen
et al
., 1998) but
this gene complement is approximately four-fold smaller than the total number of
genes in vertebrate genomes. At the level of the individual gene, there are numer-
ous instances where an invertebrate (
Drosophila
) gene has up to four related genes
(paralogues) in vertebrates, implying two rounds of genome duplication (Spring,
1997). These paralogues represent quadruplicated loci on different chromosomes
that are more similar to each other than they are to members of other tetralogous
groups. In humans, these so-called 'tetralogues' include the
HOX
genes (
HOXA
,
7p14-p15;
HOXB
, 17q21-q22;
HOXC
, 12q12-q13;
HOXD
, 2q31), the epidermal
growth factor receptor genes (
EGFR
, 7p12;
ERBB2
, 17q11.2-q12;
ERBB3
,
12q13;
ERBB4
, 2q34), the Jak family of tyrosine kinases (
JAK1
, 1p31.3-32.3;
JAK2
, 9p24;
JAK3
, 19p12-p13;
TYK2
, 19p13.2), the MADS box enhancing fac-
tors (
MEF2A
, 15q26;
MEF2B
, 19p12;
MEF2C
, 5q14;
MEF2D
, 1q12-q23), the Src
family of nonreceptor tyrosine kinases (
SRC
, 20q11.2;
YES1
, 18p11.22-p11.31;
FGR
, 1p36.1-p36.2;
FYN
, 6q21) and the syndecans (
SDC1
, 2p;
SDC2
, 8q22-q23;
SDC3
, 1p32;
SDC4
, 20q12-q13) (Spring 1997; Pebusque
et al
., 1998). Many fur-
ther examples of triplicated loci occur in the human genome (e.g. Katsanis
et al
.,
1996; Plummer and Meisler, 1999). In these cases, it may be that one paralogue
has been lost or alternatively, still remains to be characterized (Spring, 1997).
The results of studies of the genes encoding the homeobox proteins, insulin-
like growth factor genes and high mobility group proteins (Chan
et al
., 1990;
Garcia-Fernandez and Holland, 1994; Holland, 1991; Pendleton
et al
., 1993;
Sharman
et al
., 1996; see Chapter 4, sections 4.2.1,
Homeobox genes
and 4.2.3,
Insulin and insulin-like growth factor genes
) in the primitive chordates
Amphioxus
and
Ciona
, and a jawless vertebrate
Lampetra fluviatilis
(lamprey), are consistent
with the occurrence of one genome duplication in the common ancestor of all
jawed and jawless vertebrates after the lineage leading to
Amphioxus
had diverged,
and a second genome duplication occurring in the common ancestor of jawed ver-
tebrates after their divergence from the jawless vertebrates (Sidow, 1996). Studies
of
HOX
gene number suggest that the duplication events are likely to have
occurred before the radiation of the teleosts (Amores
et al
., 1998).
Gene number does not however automatically distinguish between tandem
duplications and polyploidization events. Postlethwait
et al
. (1998) mapped 144
zebrafish (
Danio rerio
) genes; comparison of the resulting map with their mam-
malian counterparts led to the identification of orthologous chromosome segments
for at least three chromosome paralogy groups in zebrafish and mammals. This
