Biology Reference
In-Depth Information
markedly from both Ftna1 and Ftna2 genes. Jury et al . (1997) attempted to explain
the creation of a solitary nonfunctional human gene in terms of a recombination
event between the two ancestral primate Ftna genes.
6.2.8 T-Cell receptor
V10 variable region gene
The 'gene' encoding the V10 variable region of the T-cell receptor
( TCRG ; 7p15)
has a single base-pair substitution in a donor splice site which serves to inactivate
the gene in humans (Zhang et al ., 1996). The counterparts of this gene in chim-
panzee and gorilla contain functional splice sites and therefore this lesion must
have occurred in the human lineage. Restoration of the defective splice site by in
vitro mutagenesis has been shown to generate a correctly spliced product.
6.2.9 Cytidine monophospho- N -acetylneuraminic acid hydroxylase gene
Humans differ from the great apes in that they lack the enzyme CMP- N -acetyl-
neuraminic acid hydroxylase which, as the name suggests, hydroxylates N -acetyl-
neuraminic acid. This cell surface sialic acid molecule is thought to be involved
in cell-cell recognition and in cell-pathogen interactions. The loss of enzyme
activity in human is caused by a 92 bp deletion in the coding region of the CMP-
N -acetylneuraminic acid hydroxylase ( CMAH ; 6p22-p23) gene (Chou et al ., 1998;
Irie et al ., 1998). This deletion results in a frameshift leading to premature termi-
nation of translation. It is specific to the human lineage since it is not found in
any of the great apes (Chou et al ., 1998) but it is not of recent origin since it has
been found to be present in Caucasians, African Americans, Japanese, Kung bush-
men and Khwe pigmies (Chou et al ., 1998). Chou et al . (1998) speculated that the
loss of N -acetylneuraminic acid hydroxylation may have had implications for sus-
ceptibility to infectious disease since some pathogens utilize sialic acids as spe-
cific binding sites on mammalian cells.
6.2.10 Flavin-containing monooxygenase 2 gene
The flavin-containing monooxygenase 2 gene is one of five FMO genes found in
mammals which encode a series of NADPH-dependent flavoenzymes that are
capable of catalyzing the oxidation of numerous drugs and xenobiotics. FMO2 is
expressed predominantly in the lung where it constitutes the major form of FMO.
The human FMO2 gene ( FMO2 ; 1q) differs from those of other mammals in that
it possesses a CAG
TAG transition converting Gln472 to a stop codon (Dolphin
et al ., 1998). This lesion predicts a truncated polypeptide lacking 64 amino acids
from its C-terminus. The FMO2 mRNA transcript is both abundant and stable.
In vitro expression studies have demonstrated that the truncated protein product
is translated, correctly targeted to the endoplasmic reticulum but has lost its cat-
alytic activity. This mutation is not present in the Fmo2 genes of gorilla and chim-
panzee and must therefore have arisen in the human lineage in the last 5-7 Myrs.
Interestingly, about 4% of individuals in African populations possess a CAG (Gln)
triplet at codon 472. It is possible that this CAG allele represents a remnant of the
original gene sequence in which case the lesion may have occurred during early
 
 
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