Genes and gene families - Human Gene Evolution - page 151

Ancestral actin gene
[intron 1, 2, 4, 5, 6, 7, 8]

↔ Substitution

Deletion
Insertion

19 aa sites ↔

Muscle actin
prototype gene

intron 5, 6

aa (-1, 4)

intron 3

∆ intron 4
↔ aa (1,17) aa 89

↔ aa
(1, 2, 3, 10)

↔ aa
(3, 298, 357)

aa 4

aa 2

aa (4,5)

aa 359

ACTG1 ACTB ACTC ACTA1 ACTA2 ACTG2

Figure 4.4. Hypothetical phylogenetic tree for the human actin gene family (after Miwa et
al ., 1991). The vertical scale is non-linear and merely represents relative evolutionary time.

Albumin genes. The human albumin gene family comprises four genes, encoding
albumin ( ALB ), -albumin/afamin ( AFM ) and group-spe-

cific component/vitamin D-binding globulin ( GC ) that are closely linked on chro-
mosome 4q11-q13 (Nishio et al ., 1996). These genes are similar in terms of their
structure and encode homologous proteins (Nishio and Dugaiczyk, 1996). A pro-
posed phylogeny for this gene family is presented in Figure 4.5 . The GC gene
appears to be the oldest member of the family; it has lost two of its original 15
exons and with them four of the original 18 disulfide bridges characteristic of the
putative ancestral protein. The AFP and ALB genes have been evolving at a par-
ticularly rapid rate (Minghetti et al ., 1985). However, the ALB gene still displays a
high degree of evolutionary conservation in terms of its sequence which is perhaps
a little surprising on account of its apparent nonessential nature evidenced by the
absence of overt clinical signs in analbuminemic humans and rats (Ohno, 1981).
Albumin is synthesized in the adult liver whereas

-fetoprotein ( AFP ),

-fetoprotein, being the fetal
counterpart of albumin, is produced in the fetal liver and yolk sac. The mecha-
nism of the developmental switch bringing about AFP gene repression and ALB
gene activation is not yet understood (Nakata et al ., 1992).
The chromosomal region containing the albumin gene cluster has been involved
in a number of pericentric inversions during the evolution of higher primates. As a
result of one such inversion, the ALB and AFP genes were translocated to the short
arm of chimpanzee chromosome 3 (analogous to human chromosome 4) (Magenis et
al ., 1987). Similar inversions in the gorilla and orangutan however left the ALB and
AFP genes on the long arm of chromosome 3 in these species (Magenis et al ., 1989).

Apolipoprotein genes. The lipoproteins are the major carriers of cholesterol,
triglycerides and other lipids in human plasma (Breslow 1985). They are encoded by
a multigene family which is dispersed but not fully dispersed in the human genome:
APOC1 , APOC2 , APOC4 , APOE (19q13.2) APOC3 , APOA1 , APOA4 (11q23), and
APOA2 (1q21-q23). The genes evolved from a primordial APOC1 -like gene, which
is thought to have existed ~680 Myrs ago, via a series of internal and complete gene
duplications ( Figure 4.6 ; Luo et al ., 1986; Boguski et al ., 1986). Since both apoA1 and