Biology Reference
In-Depth Information
human genes transcribed from the same strand is provided by the prematurely
termed growth hormone gene-derived transcriptional activator (
GHDTA)
gene
and the growth hormone 1 (
GH1
; 17q22-q24) gene (Labarrière
et al
., 1995). The
GHDTA
gene is transcribed from position -197 in the
GH1
gene promoter and
contains an open reading frame that extends from the ATG at -151 to a Stop
codon in exon 2 of the
GH1
gene. Another kind of overlap is exemplified by the
transglutaminase 1 (
TGM1
; 14q11.2) gene some of whose
cis
-acting regulatory
sequences reside within the transcribed portion of the functionally unrelated Rab
geranylgeranyl transferase
subunit (
RABGGTA
; 14q11.2) gene located <2kb
upstream of the
TGM1
transcriptional initiation site (van Bokhoven
et al
., 1996).
Clearly, the existence of overlapping genes can hamper any attempt to demarcate
precisely and unambiguously where one gene ends and another begins.
Some genes such as the immunoglobulin and T-cell receptor genes (see
Chapter 4, section 4.2.4) differ in structure between different cell types. Which
is the gene; that which is present in the germline or that which is rearranged to
perform a specific function in the soma?
Should distant regulatory sequences (such as LCRs, see section 1.1.2,
Locus con-
trol regions
) and protein binding sites that maintain chromosomal conformation be
included within the boundaries of a gene? Indeed, if we are prepared to entertain
radical redefinition of what constitutes a gene, should all parts of a gene necessar-
ily be contiguous on the same DNA strand or even the same chromosome?
At the time of writing, the majority of human gene transcripts still remain to be
characterized. However, Adams
et al
. (1995) attempted to ascribe functions to
cDNAs by limited DNA sequence analysis and detection of homologies to known
proteins. These data are summarized in
Table 1.1.
Of the human cDNAs studied by
Adams
et al
. (1995), which probably represent no more than 10% of the total num-
ber, only eight of the corresponding genes were expressed in all 30 tissues exam-
ined. Some 227 genes were expressed in >20 tissues whilst some 4300 genes were
found to be expressed in only one tissue. Clearly such data are extremely useful for
any conceptual discussion of what we mean by tissue specificity of gene expression.
Although the primary control of gene expression is usually exerted at the level
of transcription, the regulation of gene expression may also occur at several other
different stages in the pathway including transcriptional activation, mRNA splic-
ing, stability, export, translation (synthesis of the protein product), post-transla-
tional processing, and export of the mature protein (reviewed by Atwater
et al
.,
Table 1.1.
Putative functions of a sample of human genes (after Adams
et al.,
1995)
Putative function
Proportion of transcripts (%)
Cell signalling
12
RNA synthesis/processing
6
Protein synthesis/processing
15
Metabolism
16
Cell division/DNA synthesis
4
Cell structure/mobility
8
Cell/organism defence/homeostasis
12
Unclassified
24
