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Polymorphism of the vitamin D binding protein (DBP) among primates An evolutionary analysis.

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AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 73:365-377 (1987)
Polymorphism of the Vitamin D Binding Protein (DBP) Among
Primates: An Evolutionary Analysis
J. CONSTANS, C. GOUAILLARD, C. BOUISSOU, AND J.M. DUGOUJON
Centre d’Hhtotypologie, CNRS, CHU Purpan, 31300 Toulouse, France
KEY WORDS
evolution
Vitamin D binding protein, Polymorphism, Primate
ABSTRACT
The distribution of the DBP (vitamin D binding protein) polymorphism is now well characterized among human populations but for primates only limited results are known. The aim of this paper is to describe the
electrophoretic polymorphism of this protein among various species. Using
three different electrophoretic methods, we are able to detect a n unknown
polymorphism and to classify the different alleles observed. These results may
be used to set a n international nomenclature for further comparisons. The
different electrophoretic mobilities between Old and New World Monkeys show
that: 1)the Cercopithecoidea are presenting the largest genetic heterogeneity;
2) the DBP among the Galago corresponds to the lowest isoelectric points
observed among Primates; 3) during the evolution from nonhuman Primates
to Man, the DBP is able to keep its affinity for vitamin D derivatives despite
the occurrence of significant molecular modifications; 4) among Anthropo’idea,
the electrophoretic patterns of DBP are very close to the human Gcl proteins.
These results show that evolution at the DBP level can be considered as a
continuous mechanism of structural modifications. A significant transition
occurs during the differentiation between Cercopithecoldea and Anthropoi’dea.
It is not too speculative to consider that some electrophoretic forms detected
among Gorilla, Pongo, or Pan may be identical to rare variants observed
among humans.
The human vitamin D binding protein
(DBP) is a n a2 globulin, also called groupspecific component (Gc) (Daiger et al., 1975).
It is the main carrier protein of the vitamin
D derivatives in the serum. The amino acid
seq-uence has now been fully determined by
different teams (Schoentgen et al., 1985;
Yang et al., 1985; Schoentgen et al., 1986).
The most original observation obtained is its
striking similarity with albumin and alpha
fetoprotein whose loci have been syntenic on
the same chromosome for over 400,000 years
(Constans, 1984). Biochemical investigations
on the DBP revealed that the protein evolved
after triplication of the ancestral gene (Cooke
and David, 1985), but very little is known
about the different steps of the DBP modifications in the course of evolution. For these
reasons, we undertook the determination of
the DBP polymorphism among most of the
primate species living today. The aim was to
0 1987 ALAN R. LISS, INC.
present a reliable pattern of the electrophoretic mobilities of the DBP in order to develop a nomenclature for further studies and
comparisons of results between the different
laboratories. Additionally, this study attempted to identify some characteristic traits
of the DBP structure during primate evolution using human DBP as a reference.
MATERIALS AND METHODS
Serums stored a t -20°C were analysed.
These samples were provided by several laboratories as well as directly from field capture of animals in Africa and Bolivia. The
detailed list of the species investigated, the
origin of the samples, and their numbers are
included in Table 1. More than 380 animals
were studied, these representing more than
Received July 30, 1986;revision accepted January 27,1987
366
J. CONSTANS ET AL.
TABLE 1. Sera examined in this study: Animal identifications and origins
Animals
Pan
P. paniscus
P. troglodytes
Gorilla
G.g. gorilla
Pongo
P.p. abelei
P.p. pygmaeus
Papio
P. ursinus
P. hamadryas
Theropithecus
T. gelada
Macaca
M.f. fuscata
M. tonkeana
M. sylvana
Cercocebus
C. albigena
C. torquatus
C. torq x C. alb
Cercopithecus
C. nictitans
C. ascanius
C. petaurista
C. cephus
C. erythrotis
C. pogonias
c. wolfi
C. l’h. l’hoesti
C. I’h. solatus
C. l’h. preussi
C. neglectus
C. hamlyni
C. aethiops
C. mona
C. pog. x C. asc.
C. pog. x C. mona
Allenopithecus
A. nigroviridis
Miopithecus
M. talapoin
Erythrocebus
E. patas
Cebus
C. apella
Saimiri
S. sciureus
Galago
G.c. crassicaudatus
G.c. argentatus
Lemur
L.f. albifrons
L.f. mavotensis
L. catti
Coming from
- N
23
5
Yerkes RLL
Yerkes RPC
14
Yerkes RPC (13)
Zoo, France (1)
23
4
Yerkes RPC
Yerkes RPC
3
14
South Africa
Montpellier (Clin Midy), France
39
Ethiopia
30
9
Japan
Univ. Louis Pasteur (Strasbourg),
France
Zoo, France
42
18
4
7
2
1
10
1
3
1
5
1
1
7
2
23
1
4
1
St. Biol. Paimpont + CIRMF, Gabon
Station Biologique Paimpont, France
CIRMF (Gabon)
+
Station Biol. Paimpont CIRMF
Station Biologique Paimpont
Station Biologique Paimpont
Station Biol. Paimpont + CIRMF
Station Biol. Paimpont CIRMF
Station Biol. Paimpont CIRMF
Station Biol. PaimDont + CIRMF
Zoo Mulhouse M. Hist. Nat. Paris
CIRMF, Gabon
Zoo Mulhouse, France
Station Biologique Paimpont
Zoo de Mulhouse
Delta RPC + Barbados Islands
Station Biologique Paimpont
Station Biologique Paimpont
Station Biologique Paimpont
+
+
+
+ Zoo Mulhouse
5
M. Hist. Nat. Paris
3
Station Biologique Paimpont
8
Delta RPC
10
Bolivia
31
Bolivia
12
2
Oregon RPC
Oregon RPC
6
3
6
Museum #Histoire Naturelle Paris
Malaeazv
MalagaG
DBP POLYMORPHISM AMONG PRIMATES
35 taxonomic groups, and for most of these
animals, pedigree information was provided
by their breeding centers or the zoo.
The electrophoretic procedures used in this
investigation are similar to those used for
human populations: isoelectric focusing (IEF)
in a pH range 4-6 and in the presence of 3M
urea as well as polyacrylamide gel electrophoresis (PAGE)(Constans et al., 1983).
The pattern obtained after PAGE was detected by staining with a Coomassie blue
solution. When standard IEF and IEF in 3M
urea were run, the DBP band was located by
print immunofixation in cellulose acetate
strips imbedded with a n IgG antihuman DBP
solution. Some PAGE patterns were also confirmed by the immunological procedure.
Additional identity of the primate protein
with DBP protein was obtained by following
the electrophoretic shift of the protein induced by addition of a saturating dose of 25
OHDs (ethanol solution) to the serum protein
(Constans et al., 1980).
Neuraminidase treatment
Sera showing two or more DBP bands were
incubated with neuraminidase (clostridium
perfringens) at 37°C after equilibration with
a n acetate buffer pH 5.5 according to the
standardized procedure (Cleve and Patutschnick, 197913). The object of neuraminidase
treatment was to ascertain whether the additional bands were due to the presence of
sialic acid.
Time sequences were used in order to determine the number of sialic acids released by
the enzyme, and, for some experiments, the
samples were incubated overnight. Treated
samples were examined on IEF gels.
Results
The use of three electrophoretic methods
resulted in a large number of bands with
different mobilities. When the bands were
classified and compared with a human Gc21F phenotype, several distinctive patterns of
bands were found and each was characteristic of a taxonomic group (Figs. 1,2).
The effect of neuraminidase treatment on
some samples is shown in two figures (Figs.
3, 4). The isoelectric point of each band was
determined. Results are reported in Table 2.
We verified that the various DBP phenotypes
may be controlled by the existence of autosoma1 and codominant alleles at a single locus.
Allele frequencies were calculated according
367
to the Hardy-Weinberg formula, and the results are shown in Tables 3 and 4. The nomenclature used is the same as that adopted
by previous workers (Cleve and Patutschnick, 197913; Constans et al., 1983; Dykes et
al., 1985).
A single-band pattern is called Gc2 while
the double-band pattern corresponds to Gcl
proteins. Only among Galago serum was a
three-band pattern observed. It was also
called Gc’.This denomination is further documented in the text.
We called Gc2 the most frequent single
band within a species, and the less frequent
additional bands were called GcZAif the electrophoretic mobility was more anodal than
the Gc2 protein and GcZc when the mobility
was cathodal. This nomenclature gives the
electrophoretic mobility of the protein and
indicates which allele is most frequent or
rare in one species. Any new protein detected
in the future can be compared with those
included in our figures and named according
to this nomenclature.
Discussion
The DBP typing among nonhuman Primates requires the use of at least the three
electrophoretic procedures if hidden differences in the protein are to be detected between animals belonging to the same or to
different species. For this reason, it is difficult to compare our electrophoretic patterns
with those already published for DBP
(Kitchin et al., 1965; Barnicot et al., 1971;
Barnicot et al., 1972; Kitchin et al., 1967). In
some studies DBP was also confused with
“post albumin” which include some other
proteins such as alphal-antitrypsin (Lucotte
et al., 1979). The most discriminating technique is the IEF procedure with or without
urea.
The significant result obtained in this study
is the observation of different electrophoretic
forms of the DBP between any species, which
prevents any phylogenic comparison based
on electrophoretic criteria only (Lucotte and
Ruffie, 1982a). Here IEF migrations are
based on the difference between apparent
isoelectric points (PI) of the proteins. The isoelectric point of a protein is considered as a
characteristic of the molecule. It represents
a balance between electric charges located at
the surface of the protein and charges due to
its amino acid composition. Somehow the
comparison of PI may be relevant for the
368
J. CONSTANS ET AL.
l?A.G.E.
0
-
-
?IF
W21*lIt2II
2
2 A 3 2 A 2 2nr
2
2 ( l 212
2*,
- -
I -
2
2
zrz
1
xi
2('3
2
2('l
2r2
2Cl ZC2
2
(('1
l('3
1.E.E 3M-UREA
0
1-
I
-----_
I40
5 50
a-
i
0
2A1 Zr\2 2 A I 2
HOMO
'
Pan
Macaca
Gorilla
2g 1 2( 2
ZA!
2
Theropirhecus
2
21, 2c2 z('3
Papio
2
2('1
zt2
2
2('(
Z('2
Cercocebus Eryrhrocebus
Ponao
HOMlNOlDEA
><
CERCOPITHECOIDEA
Fig. 1. DBP polymorphism among Primates. IEF, IEF 3M urea, and PAGE patterns obtained
with the samples belonging to Pan, Gorilla, Pongo, Macaca, Theropithecus, Papio, Cercocebus,
and Erythrocebus species.
DBP POLYMORPHISM AMONG PRIMATES
369
F?A.G.E.
2
ZCI
2A1 2 2CS 2C1 2 C l
2A2 2Cl
2C6 2C8
ZC3 2CZ
2CI
2
2UI
2
2
2
2
2
2
2
1P 1AI 1s lC1 lC3
ICZ
2
21'2
2.41 2C1 2
21 2
2l.I 2.41
1.E.E 3M-UREA
2
ZCI
2A2 2 2CZ 2n 2C3 ZCS 2C8 2C6
2C9 2A1
7x4
2C7
1 8 IF W3 1s K2 1Ci
ZCI
1.E.E
2
ZCI
Miopithecus
2 A 2 2 ~ 1 2 2cI 2C2 ZC3 2Ck 2CS ZC6 ZCl 2C9
2C8
Cercopithecus
2 2c1
1Al IF
IS Y'1 1C2 U S
2 I('(
Zf'Z
2 A1
Allenopilhecus
Cebus
Saimri
Galago
Lemui
CERCOPITHECOIDEA
Fig. 2. DBP polymorphism among Primates. IEF, IEF 3M urea, and PAGE patterns obtained
with the samples belonging to Miopithecus, Cercopithecus, Allenopithecus, Cebus, Saymiri,
Galago, and Lemur species.
'
370
J. CONSTANS ET AL.
1 2
3
4
5
6
7
8
Fig. 3. IEF pattern obtained after neuraminidase treatment of the Pongo GclC2 protein. References,
human samples: 1,5, human Gc2-IS; 2, human Gc2; 3, Pongo GclC2; 4, 3 + neuraminidase overnight; 6,
Pongo Gc2; 7,6 neuraminidase overnight; 8, human Gc IF-1s.
+
evolution of the protein structure. From these
data (Table 2), Primates may be distributed
into three groups.
The first group consists of Cebus, Galago,
and Lemur genera. These animals are characterized by the lowest PI which corresponds
to the most primitive form of the DBP.
The second group comprises the Cercopithecoydea only. In these animals, DBP is
already more basic than that found in the
first group. Higher isoelectric points are obtained and they appear to correlate with a n
increase in positive charges due to a n accumulation of basic or neutral amino acid
substitutions.
The third group is composed of the Hominoidea whose DBP has a large PI range (ApI
0.6), which is also observed with Cercopithecus. In these animals, the extent of genetic
variation for DBP is the highest obtained.
Among Pan, five protein forms are observed. Only one allele GclF is common to
both Pan paniscus and P troglodytes. In the
P troglodytes the DBP polymorphism is more
variable with the occurrence of 4 alleles. We
confirm that the anodal band of the two-band
pattern is affected by the neuraminidase
treatment (Cleve and Patutschnick, 1979b).
As is the case with human Gcl protein, one
sialic acid molecule is present on the anodal
band. The addition of the hydroxylated vitamin D derivative (25-OH-D3)to the DBP of
Pan induces a n anodal shift of the holoprotein form as observed in man (Hay and Watson, 1977).
Among Gorilla and Pongo sera, DBP shows
the same electrophoretic pattern as the one
discussed for Pan. Three alleles are present,
GclA2 allele being common and most frequent in both the Gorilla and Pongo. No genetic variation is detected among Gorilla
while both Pongo p. abelei and Pongo p. pygmaeus have GclM and Gclc2 alleles. Only a
single Gc2band pattern was observed among
Pp, pygmaeus (Fig. 1).
These differences are in agreement with
those obtained by Bruce and Ayala (1979) on
the mobility of adenosine desaminase (ADA),
by Lucotte and Smith (1982b) on post-albumin, by Dugoujon et al. (1981, 198413) on the
Gm phenotypes of immunoglobulins, and by
Seaunez et al. (1979) on chromosome analysis. These data clearly demonstrate genetic
differences between the two orang utan subspecies.
The anodal band of the two GclC2 isoproteins is only affected by the neuraminidase
degradation and shows a mobility similar to
DBP POLYMORPHISM AMONG PRIMATES
371
1 2 3 4 5 6 7 8 9 1 0 1 1
Fig. 4. IEF patterns obtained with Galago samples
with and without neuraminidase treatment. References,
human samples. A) 1, human Gc2-1F; 2, Galago GclF1C2; 3, Galago GclS-1Cl; 4, Galago GclF-1S 5, Galago
GclF; 6, Human GclF-1s. B) 1,3,11, human Gc2-1s 2,
Human Gc2; 4, Human GclF-1s; 5, Galago GclF; 6 ,
Galago GclA1; 7, 6 + neuraminidase during 4 h; 8, 5 +
neuraminidase during 4 h; 9, 6 + neuraminidase overnight; 10,5 + neuraminidase overnight.
372
J. CONSTANS ET AL.
TABLE 2. Isoelectric points of the differentforms of the
DBP obtained after IEF migration for all the species
included in this studv
PI Range variations
Human
Pan
Gorilla
Pongo
Papio
Theropithecus
Macaca
Cercopithecus
Cercocebus
Allenopithecus
Miopithecus
Erythrocebus
Cebus-Salmiri
Galago
Lemur
I
5.30
-
4.70
5.30
-
4.75 or 4.90
5.25
5.20
5.30
5.50
5.35
5.20
5.40
5.50
4.90
4.65
4.75
5.20
5.15
5.00
4.90
5.20
5.10
5.10
5.40
4.75
4.40
4.60
that of the second cathodal band. Only one
sialic acid is released by the anodal protein
during the treatment P i g . 3). A similar
structure is present among human Gcl proteins (Constans et al., 1985).
According to the IEF mobility, the GclA2
protein seems to be very close to the human
GclF protein. Additional similarity to the
human DBP polymorphism is the simultaneous presence of the two Gcl and Gc2 protein forms in Pongo. Orang utan could be
considered as the primate closest to man.
Brown et al. (1982) gives the same hypothesis
based on molecular phylogeny while Diamond (19841, using also mDNA data, suggests a different classification.
Considering the mobilities of human DBP
variants, it is possible to find some similarities with one of the proteins observed in Pan,
Pongo, or Gorilla but it would be hazardous
to go any further in the absence of sequence
data. From the DBP variation among Hominoidea, we can conclude that Pongo and Gorilla but not Pan may originate from a
common ancestor (King and Wilson, 1975;
Schwartz, 1984). The emergence of the human species is associated with the presence
of three different alleles, GcIF, Gc", and Gc2,
which are not detected in any sample belonging to the Primate group (Constans et al.,
1985).
Among Papio, Theropithecus, and Macaca,
the DBP polymorphism is significantly less
extensive than among Hominoidea (Scheffrahn and Ziggiotti, 1981). Similar results
were observed with the immunoglobulin
markers studied by Dugoujon (1985). A single-band pattern is the usual form of DBP in
these species (Moore and Lalley, 19841, but
between them no common form of DBP is
present. The absence of polymorphism in €?
hamadryas may be due to the social structure of their groups but also to the selection
of the animals in the breeding centers. Dykes
et al. (1985) previously noted the presence of
two alleles in the same species. The Gc2 protein thus described by Dykes et al. (1985) is
probably identical with Gc2C3 in our investigation.
The DBP polymorphism in €? ursinus is
represented by three alleles, despite the fact
that only three animals were examined. No
allele common to the two Papio genera was
found. Two alleles, Gc2*l and Gc2 are observed among Theropithecus gelada. The homologous proteins are different from the ones
present in Papio or Macaca species. In Macaca syluana, DBP shows no variation. Considerable polymorphism is observed in M.
fuscata with three alleles, and M. tonkeana
differs from M. fuscata by having GcZc2and
GcZA2alleles. The unexpected observation is
that the three Macaca species did not present
any common allele. The reason of these genetic differences are not clearly understood
but it can be speculated that these results
may reflect different ancestral origins for the
three species or a severe genetic drift among
isolate groups during speciation.
Two Cercocebus species and their hybrids
were examined, the DBP polymorphism corresponds to the presence of three alleles. Gc2
is common to C. albigena and C. torquatus
and to the hybrid C. torquatus x C. albigena.
Gc2C1 protein seems to be limited to C. albigena while Gc2C2 protein is found in C. torquatus and the hybrid. These data agree with
a common ancestor between C. torquatus and
C. albigena. These species show a molecular
phenotype similar to that of the Papioninae
confirming their evolutionary closeness (Dutrillaux et al., 1982). These results have already been observed by various studies of
immunoglobulin polymorphism (Dugoujon et
al., 1981)or cytogenetic analysis (Dutrillaux,
1979; De Grouchy et al., 1978).
As we have discussed previously, genetic
divergence may have occurred and may be
responsible for the differences observed
within the Cercocebus species. In species of
the African forest such as Allenopithecus,
Miopithecus, and Erythrocebus, the DBP
polymorphism is represented by a singleband pattern as we already described for Papio, Macaca, and Cercocebus. Each band has
DBP POLYMORPHISM AMONG PRIMATES
a distinctive electrophoretic mobility. Further the PI of DBP in Erythrocebus is very
high and approaches the values observed in
some Cercopithecus samples. The Gc2C1 of
Miopithecus talapoin is also a basic protein.
It is interesting to note that DBP is quite
polymorphic in these three genera with the
presence of two or three alleles. Ruvolo (1982)
described four alleles among Erythrocebus
patas, while only three were detected in this
series. The small difference reveals the difficulty in obtaining a precise information on
protein polymorphism in animal populations
because of the selection of the samples
(breeding centers, zoo, geographical area, and
social structure of the troops) and of the limited size of the samples available for such
investigations.
Cercopithecus is probably one of the most
important and most puzzling genera in the
Primates when their history is read through
the DBP. Three points are worth noting: 1)
the DBP variability in Cercopithecus is one
of the largest among Primates (Table 2); 2)
12 alleles are detected for a total of 14 species
or subspecies or about one specific allele per
subspecies (Fig. 2); and 3) the confirmation of
a common origin for all Cercopithecus animals and probably a genetic speciation which
appeared very early; the Gc2 protein can be
considered as the oldest form as it was present in all animals examined. Similar conclusions could be drawn using other genetic
systems such as the red blood cells enzymes
(Ruvolo, 1982; Dugoujon, 19851, or the karyotype, (Dutrillaux, 1979). These data confirm
the complex nature of the evolution and speciation of Cercopithecus.
The protein Gc2C7 is present in C. neglec
tus, C. I'h. l'hoesti, and C. cephus and its
presence may be explained by the occurrence
of interbreeding between these species after
the emergence of the Cercopithecus ancestor.
It also implies that the three species were
living in the same geographic zone a long
time ago.
On the contrary, all other species have
evolved in isolated situations with specific
speciation. C. aethiops sabens is a significant
example of the genetic differentiation (Barbados isolate) occurring within a species
(Dracopoli et al., 1983). C. nictitans, C. neglectus, and C. ascanius can also illustrate a
similar analysis.
Among Cercopithecus, the determination of
the DBP polymorphism is a useful tool together with other proteins for paternity test-
373
ing, identification of the subspecies, and
identification of the hybrids. However, the
situation is different with the genera Cebus
and Sairniri.
Despite the examination of 40 samples,
DBP is monomorphic. The electrophoretic
pattern is represented by a single protein
band associated with PI values lower than
the ones obtained for Cercopithecus, Miopithecus, Allenopithecus, and Cercocebus. The
changes in the structure of DBP among Cebus and Sairniri seem to correspond to a n
intermediate step between Anthropoidea and
Prosirni in the evolution of DBP.
In contrast, among Prosimians, Galago
presents a n original pattern of the DBP polymorphism. This protein has the lowest isoelectric point in Primates (Fig. 4A). The
reason for this appears to be a n accumulation of acid residues. This observation was
confirmed by determining the number of
sialic acids in each protein band (Fig. 4-B).
GclF and GclAl proteins were treated by
the neuraminidase solution from 5 min to 24
h in order to detect successive steps of desialylation and to obtain the final protein form.
From the beginning to the end, the PI of the
DBP increased from 4.4 to 4.80. The progressive removal of sialic acids shows that the
most cathodal of the three bands (original
form) bears at least three sialic acid residues.
Each additional band possesses probably one
more sialic acid radical, giving a total of five
for the most anodal protein (PI 4.40). Since
the removal of one sialic acid residue is followed by a 0.1 pH unit shift of the PI, the
total PI variation for the anodal band (PI0.5)
confirms the presence of five sialic acid residues on this protein.
The experiment also shows that the electrophoretic heterogeneity of the DBP among
Galago is only due to posttranscriptional addition of sialic acids because, in the end, a
single band is obtained.
The well-equilibrated pattern of the three
native proteins indicates that the glycan
chains are progressively saturated by sialic
acids during posttranscriptional steps and
that sialylation is equally affected by transferases for addition of three, four, and five
sialic acids. This analysis also reveals the
existence of a t least two kinds of glycan
chains on this DBP. All those posttranscriptional modifications show that the metabolism of the DBP and of the vitamin D
derivatives is also probably exceptional in
the Galago species.
374
J. CONSTANS ET AL.
TABLE 3. Allele distribution and frequencies observed in each species and subspecies
GclAl
GclA2
-
Pan
P. paniscus
P. troglodytes
0.013
Gorilla
C.g. gorilla
Pongo
P.p. abelei
P.p. pygmaeus
Papio
P. ursinus
P. hamadryas
Theropithecw
T. gelada
Macaca
M.f. fuscata
M. tonkeana
M. sylvana
Cercoceb us
C. albigena
C. torquatus
C . torq x C. alb
Cercopithecus
C. nictitans
C . ascanius
C. petaurista
C. cephus
C . ervthrotis
C. pogonias
c . wolfi
C . l’h. l’hoesti
C. l’h. solatus
C. l’h. preussi
C . neglectus
C. hamlyni
C. aethiops
C. mona
C. pog. x C. asc.
C. pog. x C. mona
A lenopithecus
A. nigroviridis
Miopithecus
M. talapoin
Erythrocebus
E. patas
Cebus
C . apella
Saimiri
S. sciurea
Galago
G.c. crassicaudatus
G.c. argentatus
Lemur
L.f. albifrons
L.f. mayotensis
L. catta
GclF
0.9
0.895
GclS
GclCl GclC2 GclC3 Gc2A1 Gc2A2 Gc2A3
0.10
0.019
0.072
1.00
0.260
0.250
0.740
0.500
0.397
0.125
0.889
1.00
0.065
0.130
1.00
0.084
0.375
0.50
0.50
0.208
0.042
0.167
0.125
1.00
375
DBP POLYMORPHISM AMONG PRIMATES
TABLE 3. Allele distribution and frequencies observed in each species and subspecies (continued)
Gc2
x2
Gc2C1 Gc2C2 Gc2C3 Gc2C4 Gc2C5 Gc2C6 Gc2C7 Gc2C8 Gc2C9
0
0.148
0
0.100
0
0.250
0.167
0.333
0.500
0
1.00
0.603
0.315
0.833 0.042
0.875 0.125
0.875
0.750
0.857 0.071
0.750
1.00
0.95
1.00
1.00
1.00
0.700
1.00
0.50
0.113
0
1.736
0.125
0.250
0.003
0
0
0.004
0.071
0.250
0.05
0.100
0.006
0.50
0.857
0.50
0.804
1.00
1.00
1.00
0.60
0
0.100
0.100
0
0.143
0.143
0.50
0.654
0.40
0.167 0.834
0.687 0.250
0.063
0
1.00
0
0.667
0.50
0.333
0.50
0
376
J. CONSTANS ET AL.
An additional and interesting observation
among Galago is the large polymorphism,
especially, the presence of 6 alleles in G.c.
crassicaudatus. The polymorphism is represented by 4 frequent alleles; in addition,
GclAl and GclF are both G.c. crassicaudatus and G.c. argentatus.
Lemurs show the presence of four alleles
responsible for the synthesis of proteins with
low PI. These values are in the range obtained for Galago but the main difference is
the occurrence of single-band pattern. The
DBP in L.f: albifi-ons and L.f mayotensis is
polymorphic, and of the two alleles present,
Gc2C2 is common to the two subspecies.
Among L. catta, DBP is not polymorphic in
our sample and the protein detected is not
present in the other Lemur subspecies
examined.
CONCLUSIONS
metabolism is probably a key to the understanding of the molecular mechanisms responsible for the differentiation of the species
during evolution (Fontaine, 1984).This study
shows that for some species, the DBP polymorphism is limited and small whereas
among Cercopithecus as well as in the great
apes this polymorphism is more extensive.
Keeping in mind some limitations which
we analysed in this paper, such as animal
sampling, size of the group, and data on the
population structures of wild animals, only
general hypotheses can be discussed: 1)It can
be considered that a limited polymorphism
may be associated with geographical isolation and a n important genetic drift (Jones,
1986). The influence of selective forces would
be important in such a situation. 2) On the
contrary, when the DBP distribution is more
polymorphic, it can be explained by a higher
mutation rate in the course of adaptative
process. Speciation of the involved animals
would probably be more recent. Founder effect due to male behaviors and to female
reproduction are also to be taken in account
when considering the DBP polymorphism
amont Primates.
These data suggest that evolution at the
DBP level during Primate differentiation is
very likely a directional process associated
with large discontinuities during speciation.
Different patterns of protein evolution are to
be expected according to the structure of the
molecule and to the biological activity of the
protein during the fetal period and the development of the organism. This study on the
DBP among Primates is only the first step in
the investigaton of larger samples for more
detailed information at the molecular level,
in order to test the reliability of the hypotheses developed in this analysis.
DBP is present in all primate species,
though the modifications of the protein sequence are probably limited. In other words,
from Prosimi to Human, the ancestral structure of the DBP is largely maintained because of small antigenic differences between
the various DBP forms present among Primates. Polyclonal IgG antibody produced
against human DBP is able to detect the
same protein among Primates as shown in
Figures 3 and 4. This was recently confirmed
by using monoclonal antibodies (Pierce et al.,
1985).
The binding site for the vitamin D derivatives is also preserved (Hay and Watson,
1977; Adams et al., 1985) throughout Primate evolution, despite differences in the
protein structures (PI and polymorphism
variations). If minute PI variations were
underlined in this paper (the largest range
variation is from 4.4 to 5.5 for the total samACKNOWLEDGMENTS
ple examined), this value is no more than
one pH unit. Some variations are accepted
We are grateful to Dr. L.C. Lay for his
by the protein as long as the PI remains interest in this work and for his fruitful parabout 5, which probably represents a signifi- ticipation in the preparation of the manucant PI for the biological activity of the pro- script.
tein. In addition Hay and Watson (1977)
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