Biology Reference
In-Depth Information
4.1.7 Human genes whose origin preceded the divergence of animals
and fungi
We must acknowledge that man with all his noble qualities still bears in his
bodily frame the indelible stamp of his lowly origin.
C. Darwin
The Descent of Man
(1871)
The 12 068 kb sequence of the 16 chromosomes of the yeast
Saccharomyces cere-
visiae
genome has now been established (Goffeau
et al
., 1996). A considerable pro-
portion of the organism's 5885 genes are significantly related to sequences in the
human genome. Tugendreich
et al
. (1994) used the BLASTX P program to mea-
sure the extent of this homology: 29% of human cDNAs found in GenBank
matched a yeast protein with a P value of less than 10
-5
. More specifically, these
authors showed that some important human disease genes manifest considerable
sequence similarity to a yeast counterpart e.g. adrenoleukodystrophy (
ALD
,
Xq28) with a yeast 70 kD peroxisomal membrane protein, the myotonic dystro-
phy protein (
DMPK
, 19q13) with a yeast cAMP-dependent protein kinase, the
Wilms' tumor protein (
WT1
, 11p13) with a yeast zinc finger protein and the Ret
(
RET
, 10q11.2) protein underlying multiple endocrine neoplasia type 2A with a
yeast cell division control protein (Tugendreich
et al
., 1994). Similarly, human
genes
QM
(Xq28) encoding a c-
jun
-associated transcription factor (Farmer
et al
.,
1994),
SEC13L1
(3p24-25) encoding a protein putatively involved in vesicle
biosynthesis from the endoplasmic reticulum during protein transport (Swaroop
et al
., 1994),
DNECL
(14q32) encoding cytoplasmic dynein (Gibbons, 1995), the
MCM family (
MCM2
, 3q21;
MCM3
, 6p12;
MCM4
, 8q12-q13;
MCM5
, 22q13;
MCM6
, 2q21;
MCM7
, 7q21-q22) of DNA replication proteins (Kearsey and
Labib, 1998), the
PTEN
(10q23.3) tumor suppressor gene (Li
et al
., 1997) and the
G protein
-subunit gene family (Wilkie
et al
., 1992; see Section 4.2.1), have yeast
homologues.
Since
S. cerevisiae
diverged from higher eukaryotes some 1000 Myrs ago
(Doolittle
et al
., 1996), homologies between human and yeast genes are clearly
very ancient. Such conservation at the amino acid level is likely to reflect the
conservation of fairly basic biological functions. Thus, it comes as no surprise to
find that the yeast genes encoding cytochrome
c
(Wu
et al
., 1986), histone
deacetylase (Leipe and Landsman, 1997), the origin recognition complex (Gavin
et al
., 1995), the recombination protein
Rad51
(Brendel
et al
., 1997; Shinohara
et
al
., 1993) and the nucleotide excision repair gene
Rad23
(Masutani
et al
., 1994)
have highly homologous human counterparts viz.
CYC1
(8q24.3),
HDAC1
(1p34),
ORC1L
(1p32),
RECA
(15q15.1) and
RAD23A
and
RAD23B
(19p13 and
3p25, respectively).
Sometimes the homology is regionally localized, for example the GTPase-activat-
ing protein-related domain of neurofibromin (encoded by the
NF1
gene on human
chromosome 17q11.2) exhibits extensive homology to the
S. cerevisiae
proteins IRA1
and IRA2 (Xu
et al
., 1990). Such
ancient conserved regions
(ACRs) represent regions of
the greatest structural or functional importance. Eukaryotic-specific ACRs are also
evident in various other proteins with homologues in both human and yeast, for
example hexokinases,
-transducins, protein kinase catalytic domains and the Src
homology domain (Green
et al
., 1993).
