Biology Reference
In-Depth Information
(i)
Nondegenerate sites
(~65% of base positions in human codons): all possible
substitutions are nonsynonymous. The base substitution rate at these sites is
very low (
Figure 7.1
) on account of the strong selection pressure to avoid
amino acid exchanges.
(ii)
Two-fold degenerate sites
(~19% of base positions in human codons): base posi-
tions at which only one of the three possible substitutions is synonymous.
(iii)
Four-fold degenerate sites
(~16% of base positions in human codons): base posi-
tions in which all three possible substitutions are synonymous. The base sub-
stitution rate at these sites is higher than those noted for non-degenerate sites
and two-fold degenerate sites (
Figure 7.1
). The comparison of human and
rodent genes has allowed the rates of transitional and transversional silent
substitutions in four-fold degenerate sites to be estimated (1.71 × 10
-9
and
1.22 × 10
-9
per site per year, respectively) since the human-rodent divergence
(Collins and Jukes, 1994).
7.1.3 Positive and negative selection in protein evolution
It may be said that natural selection is daily and hourly scrutinizing, through-
out the world, the slightest variations; rejecting those that are bad, preserving
and adding up all that are good; silently and invisibly working, whenever and
wherever opportunity offers, at the improvement of each organic being in
relation to its organic and inorganic conditions of life.
Charles Darwin (1859)
The Origin of Species
Protein coding genes exhibit considerable variation in their rates of synonymous
(k
s
) and nonsynonymous (k
a
) substitutions (reviewed by Li, 1997). The k
s
/k
a
ratio
serves as a rough guide to the degree of evolutionary conservation and therefore
the functional constraints placed upon a protein by natural selection (Li
et al
.,
1985). Thus, some human gene sequences are very highly conserved (k
s
/k
a
ratio
high), for example ubiquitins (Vrana and Wheeler, 1996), histones H3 and H4
(Thatcher and Gorovsky, 1994), ribosomal proteins (De Falco
et al
., 1993),
H19
(Hurst and Smith, 1999), calmodulin (Thomas and Wilson, 1991), and the G pro-
tein
-subunits (Yokoyama and Starmer, 1992) indicating that these proteins have
evolved under negative or purifying selection. By contrast, other human/primate
genes have evolved very rapidly (k
s
/k
a
less than unity), for example the sex deter-
mining locus,
SRY
(Yp11.3; Whitfield
et al
., 1993), and those genes encoding
apolipoprotein C-I (
APOC1
; 19q13.2; Pastorcic
et al
., 1992), protamines P1 and
P2 (
PRM1
,
PRM2
; 16p13.3; Retief and Dixon 1993), myelin proteolipid protein
(
PLP
; Xq22; Kurihara
et al
., 1997), pregnancy-specific glycoprotein 1 and carci-
noembryonic antigen (
PSG1
,
CEA
; 19q13.2; Streydio
et al
., 1990; Teglund
et al
.,
1994), eosinophil cationic protein (
RNASE3
; 14q24-q31; Zhang
et al
., 1998), the
rhesus blood group genes (
RHD
, 1pp34-p36.2;
RHAG
, 6p11-p21.1; Kitano
et al
.,
1998) and
-microseminoprotein (
MSMB
, 10q11.2; Nolet
et al
., 1991). Such
examples of a significantly higher rate of nonsynonymous nucleotide substitution
than synonymous substitution provide strong evidence for the action of positive
selection.
Lysozyme, originally a bacteriolytic enzyme whose origin preceded the emer-
gence of the vertebrates, has been independently recruited as a digestive enzyme
