Review
Inherited Color Defects
Comparison Between Humans and Snai<es
H. Bernard Bechtel, M.D.
Dermatologists are familiar with the biogenetics and
clinical appearance of inherited color defects in
humans and other warm-blooded animals, but most
have less knowledge of analogous color defects in
snakes and other cold-blooded animals. Due to funda-
mental differences in the skin, inherited color defects
in cold-blooded animals result in unforeseen color
combinations. While skin is a protective sheath in all,
cold-blooded animals do not have the glandular ap-
pendages associated with thermoregulation, and their
pigmentary system is more complex. The primary
function of human pigmentation is to protect the or-
ganism from harmful excessive solar radiation, though
there are individual color variations in humans not
dependent on solar exposure. Pigment in snake skin
surely also blocks excess radiation, but is additionally
the basis for color patterns. Functions of color patterns
include camouflage and protective coloration, mi-
micry, deliberate conspicuousness, warning to preda-
tors, and enhancement of vision.
Pigmentation
In humans, melanin is the pigment primarily responsi-
ble for individual differences in color, and melanocytes
are the sole pigment cell type. Melanin is synthesized
from the amino acid tyrosine, and cannot be elabo-
rated without the catalyst tyrosinase. Synthesis occurs
in specialized intracellular organelles designated me-
lanosomes. Melanized melanosomes are transferred
into the keratinocytes by dendrites and distributed
through the epidermis by the outward migration of the
keratinocytes. Human skin color is related to the num-
ber, quality, and distribution of melanosomes, and no
skin color attributable to melanin is visible until the
Presented in part at the V Intercontinental Congress of Dermatology,
Caracas, Venezuela, March 10, 1991.
From private practice, Valdosta, Georgia.
Address correspondence to; H. Bernard Bechtel, M.D., 2101 North
Patterson Street, Valdosta, GA 31602.
April 1991, Vol. 30, No. 4
melanin enters the keratinocytes. Melanin in dermal
melanocytes appears blue due to scattering of light in
the overlying tissue.
Black and brown melanins are called eumelanins.
Yellow and red pigments in mammals and birds are
called phaeomelanins. Both types are derived from ty-
rosine through interrelated metabolic pathways, and
either or both eumelanins and phaeomelanins may be
found in melanocytes. Since cystine is the key compo-
nent in phaeomelanogenesis, the availability of this
substrate may determine whether eumelanogenesis or
phaeomelanogenesis occurs.
Developmental aspects of cold-blooded vertebrate
pigment cells, designated chromatophores, have been
described in depth by Bagnara.' Neural crest propig-
ment cells are pluripotential and differentiate into
three fundamentally dififerent chromatophore types:
melanophores, xanthophores, and iridophores. The
chromatophore cell type may not be specifically deter-
mined until the propigment cells reach their final desti-
nation, where they difiPerentiate in accordance with a
pattern already specified in the integument.
Melanophores are subdivided into dermal and
epidermal melanophores, and synthesize black or
brown melanin through the same biochemical path-
ways as those in warm-blooded animals. Dermal me-
lanophores participate in creating color patterns, while
epidermal melanophores are similar to human mela-
nocytes in structure, function, and location in the epi-
dermis. Xanthophores are red or yellow chromato-
phores and use pteridines and/or carotenoids as pig-
ments. Pteridine pigments are synthesized within
intracellular organelles designated pterinosomes, while
carotenoids are of dietary origin and are found in vesi-
cles interspersed among the pterinosomes. Iridophores
contain crystalline deposits of purines and participate
in pigmentation through their physical properties. In-
cident light is reflected, diffracted, and scattered, inter-
acting with the other pigments.
Dermal chromatophores determine the color pat-
tern of snakes. Xanthophores and dermal melano-
244 International Journal of Dermatology • April 1991
phores occur in a dense layer in the upper dermis, their
distribution and arrangement, color, and quality of
color corresponding to the overlying color pattern. Im-
mediately beneath this layer is a parallel band of irido-
phores. The density of cells in this layer is variable and
related to the colors in the pattern. Individual snakes of
the same species vary in quantity, quality, and inten-
sity of colors, and there are also geographic differences,
possibly accounted for by interaction of additive al-
leles.
Albinism
Albinism is an inherited failure of melanocytes to pro-
duce normal amounts of melanin in eyes, skin, or
both, and occurs in warm- and cold-blooded animals.
Although individual occurrence of albinism is uncom-
mon, it has been recorded in nearly every animal of
which adequate numbers have been observed. The
most widely known form of albinism in humans is
oculocutaneous: absence of melanin in skin, hair, and
eyes. The skin of human oculocutaneous albinos is
pinkish white (Fig. 1), there is an excess of lanugo hair,
and the regular hair is fine, silky, and pale yellow. The
pupils are red and the irides pink or bluish. This type of
albinism is inherited as an autosomal recessive gene
mutation, occurs in all races, and albino skin is basi-
cally similar in all races.
Albino Snakes
Oculocutaneous albinism is well known in snakes.^
Additional inherited color defects occur in snakes,
based on the presence of multiple chromatophore
types.
The biogenetics of oculocutaneous albinism in
snakes are the same as in humans. Melanin is absent
from skin and eyes, and also the tongue, but albino
snakes are not white. Xanthophores and iridophores
are unaffected by the albino mutation, and they deter-
mine the color pattern in albino snakes. Many albino
snakes are brightly colored, often in unanticipated
ways, and not all hypomelanistic snakes are albinos.
The black ratsnake, a large, harmless snake occur-
ring in the eastern United States, is typically a plain,
shiny black snake.^ However, many xanthophores and
iridophores participate in the chromatophore mix of
this snake, though their presence is only hinted at by
the traces of white, yellow, orange, or red barely visible
in the skin between the scales of the normal snake. As a
result, most albino black ratsnakes are yellowish with
prominent pink blotches.
The eastern diamondback rattlesnake (Fig. 2A), a
large, venomous snake occurring in the southeastern
Vol. 30
coastal plain of the United States, has a predominance
of yellow xanthophores in the color mix, and the yel-
low diamond pattern is clearly evident even in an ocu-
locutaneous albino specimen (Fig. 2B).
Diminished melanosynthesis can result from de-
creased synthesis of tyrosinase, unavailable free tyro-
sine, or the presence of tyrosinase inhibitors. At pres-
ent, two forms of oculocutaneous albinism have been
identified in humans: tyrosinase-negative and tyrosi-
nase-positive, based on the capacity of melanocytes in
hair follicles to synthesize melanin when incubated in
tyrosine."* Both are inherited as simple recessive traits
and each is the result of the action of nonallelic auto-
somal genes. Both types of albinism also occur in
snakes, and have been demonstrated in two genera^''
with the dopa reaction. Epidermal melanophores of
albino snakes are visible in frozen sections as large,
clear cells in the basal layer. When the skin of a tyros-
inase-positive albino snake is incubated in dopa, the
epidermal melanophores, including their dendrites,
become densely packed with dark granular intracyto-
plasmic pigment, while the dermal melanophores de-
velop little or none.
Snakes periodically shed the skin in a single
sheath, including a clear, transparent eye cap. Fre-
quency is determined by specific differences and envi-
ronmental factors such as nutrition. This has been de-
scribed histologically.^'^ Following a shed, after a brief
resting period, a rapid proliferation of new basal cells
occurs. Shortly before the cast, the outer layer of the
now thicker epidermis keratinizes, and separates from
the remaining epidermis at the time of casting. The
exact nature of the cleavage is not understood. The
color pattern of any snake is most brilliant immedi-
ately following a shed, and becomes dull as the cycle
continues, probably because of continuous melano-
genesis by the epidermal melanophores. The pattern of
most snakes can be discerned by examination of the
cast skin against light, while the cast skin of albino
snakes contains no pigment and is clear and trans-
parent.
Snakes with partial albinism have been collected.
In the case of the black ratsnake, a multiple allele sys-
tem is known to occur at the locus for tyrosinase-posi-
tive albinism, involving recessive genes for oculocu-
taneous albinism and a partial albinism with pig-
mented eyes.*
Axanthic Snakes
Snake xanthophores and melanophores are under sep-
arate genetic control and are inherited independently.
A somatic recessive mutation resulting in axanthism
occurs. Melanophores and iridophores are unaffected
No. 4 Color Defects in Humans and Snakes • Bechtel 245

back rattlesnake, are bluish (Fig. 2C), and all retain

their pattern. Nonallelic forms of axanthism are
known for at least one species,' apparently analogous
to nonallelic forms of albinism, though the biochemis-
try of pterinosome synthesis is not as well known as
melanogenesis.
White tigers have some parallels to axanthic
snakes. Both are inherited as a recessive mutation and
both have similar color defects.

Leucistic (White) Snakes

Figure 1. Oculocutaneous albino child.
by the axanthic mutation, and they determine the
color pattern of axanthic snakes.
The harmless mud snake of the southeast is a large,
iridescent black snake with a red or pink underside.^
The underside of axanthic mutants is plain white.
Some axanthic mutants, such as the eastern diamond-
Leucistic mutants occur in reptiles and amphibians.
Leucistic snakes are white with dark eyes and have no
residual pattern (Fig. 2D). This color anomaly appears
to be even more uncommon in wild populations than
albinism or axanthism, but has been reported in sev-
eral snake species, neotenic Mexican axolotls (amphib-
ians), and the American alligator. The eastern dia-
mondback rattlesnake is the only snake with literature
reports of all three color anomalies.'" In one snake, the
Texas ratsnake, leucism has been demonstrated to be

Figure 2. Eastern diamondback rattlesnake. (A, top left) Normally pigmented. (B, top right) Ocu-
locutaneous albino. (C, bottom left) Axanthic. (D, bottom right) Leucistic.
246 International Journal of Dermatology • April 1991 Vol. 30

caused by a somatic recessive mutation." Microscopic
examination of frozen sections of biopsies from this
snake reveal diminished numbers of iridophores and
no visible melanophores or xanthophores. This agrees
with the findings reported for the white neotenic Mex-
ican axolotl.'^
Acknowledgments
Bill Love (Belle Glade, FL) provided the photograph of the leucistic
snake and Robert Simons (Gainesville, FL) provided the photograph
of the axanthic snake.
References
1. Bagnara J. Developmental aspects of vertebrate chromato-
phores. Am Zool. 1983;23;465-.478.
2. Hensley M. Albinism in North American Amphibians and Rep-
tiles. East Lansing, Ml; Museum of Michigan State University,
1959;133-I59.
3. Conant R. A Field Guide to Reptiles and Amphibians of the
United States and Canada. 2nd ed. Boston; Houghton Mifflin,
1975;176, 193.
4. Witkop CJ Jr, Nance WE, Rawls RF, et al. Autosomal recessive
oculocutaneous albinism in man; Evidence for genetic hetero-
genicity. Am J Hum Genet. 1970;22;55-74.
5. Bechtel HB, Nelson JW, Bechtel E. Histochemical demonstra-
tion of two types of albinism in San Diego gopher snakes {Pituo-
phis melanoteucus annectens) by use of dopa reaetion. Copeia.
1980;4;932-935.
6. Bechtel HB, Bechtel E. Albinism in the snake, Elaphe obsoleta. J
Herpetol. 1981;15;397-402.
7. Bechtel HB. Some microscopic aspects of ecdysis in snakes.
Herpetologica. 1957; 13; 177-181.
8. Maderson PFA. Histoiogical changes in the epidermis of snakes
during the sloughing cycle. J Zool Lond. I965;146:98-l 13.
9. Bechtel HB, Bechtel E. Color mutations in the corn snake
(Etaphe gutlala guttata): Review and additional breeding data. J
Hered. 1989;80;272-276.
10. Antonio FB, Barker JB. An inventory of phenotypic aberrancies
in the eastern diamondback rattlesnake (Crotalus adamanteus).
HerpRev. 1983; 14; 108-110.
11. Bechtel HB, Bechtel E. Genetics of color mutations in the snake,
Elaphe obsoteta. J Hered. 1985;76;7-11.
12. Frost SK, Brigg F, Malacinski M. A color atlas of pigment genes
in the Mexican axolotl (Ambystoma mexicanum). Differentia-
tion. 1984;26;182-188.

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