102
FRED H. WILT
different from the adult, is now beyond dispute (McCutcheon, 1936;
Riggs, 1951-1952). Furthermore, the tadpole Hb is probably heterogeneous. Frieden (1961) examined tadpole Hb by paper electrophoresis
and found one band, which was distinctly different from the adult Hb.
Also, the sedimentation of tadpole Hb was usually at 4.35 S, rather
than the higher sedimentations observed for the adults (Trader et al.,
(1963). Baglioni and Sparks (1963) found three distinct Hb types in
tadpoles after application of starch-gel electrophoresis. The three fractions produced slightly different "fingerprints," and electrophoresis in
urea revealed two subunits for each type of Hb. A given Hb differed in
either subunit (but not both) from the other subunits of the two Hb
types. One of the tadpole Hb classes appeared to be quite similar to one
of the adult Hb types. Hamada et al. (1964) separated three Hb types
from tadpoles by chromatography on carboxymethyl cellulose and each
of the tadpole Hb's differed from their adult homologs. They also differentiated between tadpole and adult Hb by electrophoresis, UV absorption spectrum, sulfhydryl content, denaturation rate, and oxygen association equilibria. Finally, Moss and Ingram (1965) examined tadpole
Hb by polyacrylamide-gel electrophoresis. There was one major component and four minor components. Electrophoresis of reduced and
alkylated Hb at low pH in urea showed one major band and two minor
bands; these are presumably the subunit classes of tadpole Hb.
E. Shift from Embryonic to Adult Hemoglobin
It is obvious from the foregoing, that profound changes in the types
of Hb occur during development. The fundamental question in the context of this article is what are the kinds of control mechanisms which
result in cessation of embryonic Hb synthesis and initiation of adult
Hb synthesis. In the human, you will recall, the change from HbF to
HbA only involves cessation of γ-chain synthesis and initiation of
/?-chain synthesis. Hecht et al. (1966) have recently shown Hb Gower 1
and Hb Gower 2 are predominant in very young human embryos. This
suggests that the synthesis of an c-globin chain precedes synthesis of
ß- and γ-chains in the human embryo. The synthesis of ß- and γ-chains
actually occurs simultaneously, and only the proportions of the two
gradually shift. The description of this change and experiments on the
mechanisms involved have been recently summarized by Baglioni (1963).
Two sorts of mechanisms, not mutually exclusive, have been proposed.
First, it is possible that the well known changes in principal sites of
hematopoiesis could be responsible for the change from HbF to HbA;
but as Baglioni points out, the facts are not in accord with this hypothesis. A given erythrocyte may contain both HbA and HbF, and studies
on the synthesis of Hb by cells from different organs show both HbA
FRED H. WILT
different from the adult, is now beyond dispute (McCutcheon, 1936;
Riggs, 1951-1952). Furthermore, the tadpole Hb is probably heterogeneous. Frieden (1961) examined tadpole Hb by paper electrophoresis
and found one band, which was distinctly different from the adult Hb.
Also, the sedimentation of tadpole Hb was usually at 4.35 S, rather
than the higher sedimentations observed for the adults (Trader et al.,
(1963). Baglioni and Sparks (1963) found three distinct Hb types in
tadpoles after application of starch-gel electrophoresis. The three fractions produced slightly different "fingerprints," and electrophoresis in
urea revealed two subunits for each type of Hb. A given Hb differed in
either subunit (but not both) from the other subunits of the two Hb
types. One of the tadpole Hb classes appeared to be quite similar to one
of the adult Hb types. Hamada et al. (1964) separated three Hb types
from tadpoles by chromatography on carboxymethyl cellulose and each
of the tadpole Hb's differed from their adult homologs. They also differentiated between tadpole and adult Hb by electrophoresis, UV absorption spectrum, sulfhydryl content, denaturation rate, and oxygen association equilibria. Finally, Moss and Ingram (1965) examined tadpole
Hb by polyacrylamide-gel electrophoresis. There was one major component and four minor components. Electrophoresis of reduced and
alkylated Hb at low pH in urea showed one major band and two minor
bands; these are presumably the subunit classes of tadpole Hb.
E. Shift from Embryonic to Adult Hemoglobin
It is obvious from the foregoing, that profound changes in the types
of Hb occur during development. The fundamental question in the context of this article is what are the kinds of control mechanisms which
result in cessation of embryonic Hb synthesis and initiation of adult
Hb synthesis. In the human, you will recall, the change from HbF to
HbA only involves cessation of γ-chain synthesis and initiation of
/?-chain synthesis. Hecht et al. (1966) have recently shown Hb Gower 1
and Hb Gower 2 are predominant in very young human embryos. This
suggests that the synthesis of an c-globin chain precedes synthesis of
ß- and γ-chains in the human embryo. The synthesis of ß- and γ-chains
actually occurs simultaneously, and only the proportions of the two
gradually shift. The description of this change and experiments on the
mechanisms involved have been recently summarized by Baglioni (1963).
Two sorts of mechanisms, not mutually exclusive, have been proposed.
First, it is possible that the well known changes in principal sites of
hematopoiesis could be responsible for the change from HbF to HbA;
but as Baglioni points out, the facts are not in accord with this hypothesis. A given erythrocyte may contain both HbA and HbF, and studies
on the synthesis of Hb by cells from different organs show both HbA