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Evidence for the unique function of docosahexaenoic acid (DHA) during the evolution of the modern hominid brain



The African savanna ecosystem of the large mammals and primates was associated with a dramatic decline in relative brain capacity associated with little docosahexaenoic acid (DHA), which is required for brain structures and growth. The biochemistry implies that the expansion of the human brain required a plentiful source of preformed DHA. The richest source of DHA is the marine food chain, while the savanna environment offers very little of it. Consequently Homo sapiens could not have evolved on the savannas. Recent fossil evidence indicates that the lacustrine and marine food chain was being extensively exploited at the time cerebral expansion took place and suggests the alternative that the transition from the archaic to modern humans took place at the land/water interface. Contemporary data on tropical lakeshore dwellers reaffirm the above view with nutritional support for the vascular system, the development of which would have been a prerequisite for cerebral expansion. Both arachidonic acid and DHA would have been freely available from such habitats providing the double stimulus of preformed acyl components for the developing blood vessels and brain. The n-3 docosapentaenoic acid precursor (n-3 DPA) was the major n-3-metabolite in the savanna mammals. Despite this abundance, neither it nor the corresponding n-6 DPA was used for the photoreceptor nor the synapse. A substantial difference between DHA and other fatty acids is required to explain this high specificity. Studies on fluidity and other mechanical features of cell membranes did not reveal a difference of such magnitude between even alpha-linolenic acid and DHA sufficient to explain the exclusive use of DHA. We suggest that the evolution of the large human brain depended on a rich source of DHA from the land/water interface. We review a number of proposals for the possible influence of DHA on physical properties of the brain that are essential for its function.
Evidence for the Unique Function of Docosahexaenoic
Acid (DHA) During the Evolution of the Modern
Hominid Brain.
Crawford MA1, Bloom M2, Leigh Broadhurst C3, Schmidt WF3, Cunnane
SC4, Galli C5, Ghebremeskel K1, Linseisen F2., Lloyd-Smith J2 and
Parkington J6
Lipids 2000, 34: S39-S47
1. Institute of Brain Chemistry and Human Nutrition, University of North London,
London N7 8DB UK.
2. Dept of Physics, University of British Columbia, Vancouver V6T 1Z1. 3. USDA
3 United States Department of Agriculture, Environmental Chemistry
Laboratory, NMR Facility, Beltsville, MD 20705, USA.
4. Dept Nutritional Sciences, Faculty of Medicine, University of Toronto, Ontario M5S
3E2, Canada.
5. Institute of Pharmacological Sciences, Milan 20133, Italy.
6. Archaeology Department, University of Capetown, South Africa.
Crawford MA 1, Bloom M2, Broadhurst CL3, Schmidt WF3, Cunnane SC4, Galli C5
Gehbremeskel K1, Linseisen F2, Lloyd-Smith J2 and Parkington J6,
1. Institute of Brain Chemistry, London N7 8DB UK. 2. Dept of Physics, University of
British Columbia, Vancouver V6T 1Z1. 3. USDA Beltsville, Environmental Chemistry
Laboratory, MD 20705, USA. 4. Dept Nutritional Sciences, University of Toronto,
Ontario M5S 3E2, Canada. 5. Institute of Pharmacological Sciences, Milan 20133, Italy.
6. Archaeology Department, University of Capetown South Africa.
The African savanna ecosystem of the large mammals and primates was associated with a
dramatic decline in relative brain capacity. This reduction happened to be associated with a
decline in docosahexaenoic acid (DHA) from the food chain. DHA is required for brain
structures and growth. The biochemistry implies that the expansion of the human brain
required a plentiful source of preformed DHA. The richest source of DHA is the marine
food chain while the savannah environment offers very little of it. Consequently H.
sapiens could not have evolved on the savannahs. Recent fossil evidence indicates that the
lacustrine and marine food chain was being extensively exploited at the time cerebral
expansion took place and suggests the alternative that the transition from the archaic to
modern humans took place at the land/water interface.
Contemporary data on tropical lake shore dwellers reaffirms the above view.
Lacustrine habitats provide nutritional support for the vascular system, the development of
which would have been a prerequisite for cerebral expansion. Both arachidonic acid (AA)
and DHA would have been freely available from such habitats providing the double
stimulus of preformed acyl components for the developing blood vessels and brain.
The ω3 docosapentaenoic acid precursor (ω3DPA) was the major ω3 metabolite in
the savanna mammals. Despite this abundance, neither it or the corresponding ω6DPA
were used for the photoreceptor nor the synapse. A substantial difference between DHA
and other fatty acids is required to explain this high specificity. Studies on fluidity and
other mechanical features of cell membranes have not revealed a difference of such
magnitude between even α-linolenic acid (LNA) and DHA sufficient to explain the
exclusive use of DHA. We suggest that the evolution of the large human brain depended
on a rich source of DHA from the land/water interface. We review a number of proposals
for the possible influence of DHA on physical properties of the brain that are essential for
its function.
Key words: arachidonic, brain, blood vessels, docosahexaenoic, evolution, lacustrine,
marine foods, membranes, nutrition, Nyasa, Turkana, Australopithecus, H. erectus, H.
For the first 2.5 billion years of life on the planet, the blue-green algae dominated the proto
oceans. The photosynthesis of the algae produced complex molecules including proteins,
carbohydrates and lipids which were rich in ω3 fatty acids. Based on the explosion of the
phyla in the fossil record, oxidative metabolism became predominant about 600 million
years ago. Thus animals, visual, nervous systems and brains evolved in a DHA rich
environment (1). DHA is the most prominent essential fatty acid used for the structures
and functions of the photoreceptor and synaptic junction. So the question addressed in
this paper is why, and what are the evolutionary implications of the abundance of DHA in
the marine food chain compared the relatively paucity in land ecosystems.
The dominance of ω3 fatty acids in the early oceans was associated with fish and reptiles
requiring ω3 fatty acids for their reproduction. This dominance persisted until the end of
the Cretaceous period, 70 million years ago. In the wake of the extinction of the giant
reptiles, cycads, ferns and their allies, the flowering plants appear in the fossil record.
They stored lipids, for energy during germination, containing seed oils rich in
6 fatty
acids. Then, a new set of species, the mammals, evolved: it may not be a coincidence that
they required ω6 fatty acids for their reproduction.
Mammalian brain size is larger in relation to body size compared to the previous egg laying
amphibians, reptiles and fish. The difference could be explained by the evolution of the
placenta. The placenta enables nutrients and energy to be focused continuously on the
development of one or a small number of progeny throughout the critical time of brain
development. In the human, 70% of the calories transferred by the placenta to the fetus is
devoted to brain growth. The placenta is a rapidly growing vascular system with a high
requirement for ω6 fatty acids especially AA. In 42 species so far studied, AA and DHA
are major acyl constituents with the precursors being virtually absent. So the emergence of
the ω6 fatty acids may have added the missing biochemical link, liberating genetic
potentials for vascular development and hence the evolution of the placenta, mammary
gland and the larger brains of the mammals.
The difference between species is not the chemistry but the extent or size to which the brain
is developed (1). The manner of these differences is so large as to imply the availability of
AA and DHA were limiting factors in the evolution of the brain (1,2). Indeed, the need for
both ω6 and ω3 fatty acids for development and health of the vascular system and brain
has long been recognised (3.).
The accepted dogma regarding the evolution of Homo sapiens is that he was originally a
hunter and gatherer on the African savanna. A study of savanna and other African species
show that as they evolved larger and larger bodies, the relative size of the brain diminished
logarithmically with increase in body weight (1,4). A cebus monkey of 0.9 kg body
weight has 2.3% of its body weight as brain, a 60 kg chimpanzee 0.5%. The larger gorilla
at 110 kg has only 0.25% brain which is physically smaller than the chimpanzee’s brain.
At the extreme, the one ton rhinoceros has <0.1% with its brain weighing only 350g. It
reaches that massive one ton body weight at four years of age.
Why does size and velocity of growth matter? The reason is that the biosynthesis of AA
and DHA is relatively slow, and may not be able to keep pace with body growth in fast-
growing animals. Rats and mice desaturate and chain elongate the parent essential fatty
acids to produce larger amounts of AA and DHA than their precursors. Stepping up in
size from the guinea pig to the wild pig the impact of velocity of growth results in a
progressive decline in AA and DHA whilst the precursors linoleic and α-linolenic acids
become more dominant in liver lipids (1). Instead of DHA, the
3DPA is now the major
metabolite of
-linolenic acid (5).
So the faster an animal grows, the larger it becomes and the greater is the constraint of the
biosynthesis of AA and DHA. The large savanna, mammals of Africa all shared the same
fate namely, DHA and brain capacity declined as body size accelerated. The important
issue is that desaturation and elongation in these large mammals peters out at the ω3DPA
with relatively little DHA being synthesized. What little DHA is synthesized is used in the
brain and photoreceptor. The abundant ω3DPA is not found here. Brain size was
sacrificed not brain DHA (1, 6). This fact raises two issues:
The savanna food chain on which Homo sapiens is supposed to have evolved is fairly
devoid of DHA so how did Homo evolve a large brain?
Why was the more readily available ω3DPA not used for the brain instead of DHA?
M odern human intellect and brain-specific nutrition .
Australopithecus spp. are unremarkable in their apparent encephalization throughout their
evolutionary history as far as can be deduced from the fossil record . No australopithecine
has a cranial capacity much over 500 cm3 (7 ), despite the existence of the genus for over 3
Myr. Contrast this to genus Homo, whose cranial capacity doubled from H. erectus to H.
sapiens in a span of at most 1 Myr (Table 1). The Homo spp. fossil evidence and
encephalization quotient (EQ ) values do not support a slow, linear Darwinian progession
towards modern intelligence, but rather a sudden, exponential growth of relative brain size
in the last 200,000 years or so.
The earliest evidence for modern H. sapiens is found in Africa. Homo spp. in general are
associated with lake shore (lacustrine) environments in the East African Rift Valley, while
Australopithecines are associated more with forested areas (8,9). Thus far, evidence for
precocious cultural development of Homo sapiens is exclusively confined to lacustrine and
coastal marine environments. Lakeshore sites in the Rift Valley have yielded fairly
sophisticated stone tools as old as 260 kyr associated with H. sapiens remains. The
implications of this land/water habitat providing brain specific nutrients has largely been
Table 1. Mean brain volumes and encephalization quotients (EQ) for selected hominoid
species. EQ1 from the calculations of Martin (4); EQ2 from the calculations of Harvey
and Clutton-Brock (47).
Species Brainvolume (cm3) EQ1 EQ2
A. afarensis 384 1.23 1.45
A. africanus 420 1.31 1.62
A. boisei 488 1.37 1.72
A. robustus 502 1.49 1.92
H. habilis 579-597 1.74-1.79 2.10-2.29
H. rudolfensis 709 1.41 2.11
H. erectus 820-844 1.59-1.63 2.38-2.44
H. sapiens 1250 3.05 4.26
P. troglodytes 410 1.25 1.57
Fossils from coastal sites on the southern Cape of South Africa are widely regarded as the
earliest modern human fossils (10,11,12). At numerous sites along the Cape, hominid
occupation is evidenced dating from 120 to 60 kyrs before now. Modern human fossils
dating to about 100 kyr have been recovered at Klasies River Mouth and Border Cave are
found associated with incontrovertible evidence for the consumption of seafoods dating to
the time of rapid cerebral expansion (10,13,14,15).
Parkington (15) points out that in coastal hunter-gatherer cultures, women are responsible
for collecting shellfish. So stone age women could have easily provided themselves with a
plentiful source of brain-specific nutrition, even when strength/mobility are compromised
during pregnancy and lactation. Children would have naturally participated in exploitation
of, at that time, this extremely rich resource. Early consumption of shellfish is also present
in the archaeological record on the Mediterranean coast of Africa. It is likely to have
occurred elsewhere as well, however most possible coastal sites which could be
investigated have been obliterated by the higher sea levels of the current interglacial era.
Successful e arly Homo spp. were Tropical Coastal Migrants
Both H. erectus and H. sapiens sucessfully colonized areas outside of Africa. There is all
but unanimous agreement amongst paleoanthropologists that H. sapiens originated in
Africa and then spread throughout the world (16 ,17, 18,19). Recently, stone tools of 0.8-
0.9 Myr have been found on the island of Flores, one of the Wallacean islands lying
between Java and Timor in Indonesia (20). The antiquity of the specimens suggests they
were manufactured by H. erectus, not H. sapiens. Although Java and Bali were
periodically connected to the mainland during the Pleistocene glaciation, even at times of
lowest sea level, reaching Flores would have required a sea crossing of at least 19 km.
This implies that at least in Indonesia, H. erectus had already reached the cognitive
capability to build and use watercraft repeatedly.
Previous to Morwood et al.’s (20) recent discovery, the earliest evidence for the use of
watercraft dates from about only 40 kyr or slightly earlier with the migration of H. sapiens
from the Wallacean Islands to Australia. That initial colonization of Australia, Tasmania
and New Guinea was accomplished by modern H. sapiens. Similar to the movements of
H. erectus, these early migrants are considered to have followed a tropical coastal route.
Therefore, both the earliest occurrence of modern H. sapiens, the earliest use of watercraft
and successful colonization of Southeast Asia were intimately associated coastal migrations
and with the utilization of food resources from the marine food chain.
We consider this association not accidental nor coincidental, but a reflection of the dramatic
influence of brain specific nutrition on the evolutionary process. We do not accept the
postulate that H. sapiens a priori evolved a large, complex brain, then began to hunt in
order to maintain it--the brain must come first.
Our thesis is that there must have been enough long chain polyunsaturated fatty acids (LC-
PUFA) available in the diet to:
1. Provide many generations of hominids with fuel for fetal/infant development as well as
childhood and adult needs for the cardio-vascular system and the brain.
2. Allow for substantial amounts of 18 carbon polyunsaturated fatty acids (PUFA) which
would have been oxidised for energy requirements (21,22 ).
3. Explain and allow for our inefficient conversion of LA to AA and LNA to DHA (which
is illustrated by preferential incorporation of DHA in the infant brain (23) and
improved problem solving in infants fed DHA which persisted beyond the period of
supplementation (24)).
The evidence on the extensive coastal and lacustrine exploitation implies LC-PUFA were
consistently abundant in the food supply as we evolved. Homo did not however, go as far
as the obligate carnivores in which the desaturation process is barely detectable (25). If H.
sapiens had developed his intellect by evolving into a primate which can make heroically
efficient use of 16 and 18 carbon PUFA from vegetarian sources, we would see an
obvious signature in our current PUFA metabolism, since we are only a 300-100 kyr old
species. Instead we see the opposite. We might hypothesize that Australopithecus spp.
could not mount this heroic metabolic effort either which explains why their brain capacity
was constrained by their land based diet at 400 -500 cc for 3 Myr and explains why
exploitation of coastal foods fits with the rapid and recent cerebral expansion to 1.3 kg after
3 Myr of a static brain size (9,15).
The human brain requires a rapidly developing heart and vascular system to meet the
prodigious energy and nutrient demand during its development. The vascular system itself
has a high requirement for AA (26). Hence the principles of vascular development were
sine qua non vital for the final evolution of the large human brain.
If we now examine the contemporary evidence on cardiovascular disease we find that land
based animal fats have been causaly linked to heart disease as revealed by the Seven
Countries study of the 1950s and even earlier (27). Saturated fats and vascular
degeneration would be incompatible with CNS expansion. Also, there is increasing
evidence that cardio-vascular disease has its origin in poor fetal nutrition (28) consistent
with our hypothesis of long term, multi-generation effects operating on vascular and CNS
evolution. Those forces can act for expansion or degeneration.
Worldwide diets and cardiovascular risk factors show that marine fats, especially DHA, are
cardioprotective (29,30, 31). It is well known that people living on sea foods have low
cardiovascular risk factors. The diet of contemporary populations beside East African
lakes (Lake Nyasa and Lake Turkana) is still largely based on fish rich in ω3 and ω6 LC-
PUFA. From Table 2, calculated intakes of ω3 LC-PUFA are 1-4 g/d and AA 0.5-1.0
g/d, compared with ω3 LC-PUFA 0.2-0.3 g/d and AA 0.1-0.2 g/d for populations
consuming Western diets. Total dietary fat in the African populations is similar at 10-15%
of the dietary energy (32).
Table 2. The FA composition data of the fish from Lake Nyasa and Turkana (wt% of fatty
acids): Turkan
Perch Nyasa
Mfui Nyasa
Kambale Nyasa
Carp Nyasa
cat fish
Fat g% wet
weight 2.3 2.6 1.1 1.8 4.9 10.3
20:4ω6 8.4 7.7 8.0 5.8 5.8 4.3
20:5ω3 2.8 1.8 3.1 2.2 1.8 4.2
22:5ω3 3.2 3.8 3.7 5.2 5.0 1.8
22:6ω3 15.7 18.1 19.1 13.3 7.8 8.6
We have compared East African lake shore, mainly vegetarian and Europeans
cardiovascular risk factors (Table 3). Blood cholesterol, blood pressure, lipoproteins
(Lp(a)) are lower in the contemporary Africans living on lake shores of Turkana and Nyasa
compared to their vegetarian cousins and Europeans. Plasma AA, eicosapentaenoic acid
and DHA are highest in the fish eating, lake shore people and least in the vegetarian or
omnivorous inland cousins. Furthermore, comparison of children from the lake shore
versus European children living in East Africa showed that the two populations can be
separated on the basis of blood cholesterol at the age of 6 years! Whilst the European
children’s blood pressure and cholesterol continues to rise the Africans remain stable
illustrating the compatibility of the lacustrine diet with good cardiovascular performance
and the needs of fetal brain expansion. It is of interest that the Turkana have the highest
mitochondrial DNA diversity of any ethnic group. In fact 36 Turkana people have a higher
diversity than the world-wide population database. The simplest interpretation is that
humans date back to the East African Rift Valley (33).
Table3. Comparison of cardiovascular risk fatty factors, plasma and fish fatty acid
composition of lake shore, fish eating vegetarian and European, communities in the Rift
Valley and East Africa.
Populations Largely vegetarian Lake shore Significance of
Differences ___
Plasma lipids (mg/dL) p
Plasma T C 136. ± 39.8 n=686 122 ± 30.9 n=622 < 0.05
Plasma TG 105 ± 53.1 80.6 ± 40.7 <0.001
Lp(a) 32.3 ± 22.4 19.9 ± 17.7 <0.001
Blood pressure (mmHg)
Nyasa Systolic 135 ± 20.4 120 ± 15.1 <0.001
Diastolic 77.6 ± 10.6 70.5 ± 8.9 <0.001
Turkana Systolic European El Molo
Age yrs 0-3 82 ± 14 n=15 85 ± 9.7 n=6 ns
6-10 98 ± 22 n=16 87 ± 17 n=16 ns
16-20 90 ± 28 n=24 119 ± 28 n=14 <0.001
25-45 31± 34 n=265 105 ± 30 n=24 <0.001
Cholesterol 0-3 102 ± 24 n=15 97 ± 18 n=12 ns
mg/dl 6-8 167 ± 35 n=18 112 ± 32 n=16 <0.01
25+ 228 ± 44 n=145 147 ± 49 n=24 <0.001
Plasma FA (wt %)
Lake Nyasa
LA 14.8 ± 4.30 n=53 23.9 ± 4.37 n=53 <0.002
LNA 0.60 ± 0.20 0.31 ± 0.14 <0.001
AA 8.26 ± 1.94 9.85 ± 2.68 <0.005
EPA 0.72 ± 0.22 2.48 ± 1.35 <0.001
DHA 1.48 ± 1.04 5.93 ± 1.77 <0.001
Lake Turkana , El Molo* n=32 Bantu n=98 European n=124
LA 9.3 ± 3.0 22.8 ± 4.8 19 ± 4.9
DHLA 1.9 ± 0.7 3.5 ± 1.3 2.4 ± 1.1
AA 12.2 ± 3.8 5.1 ± 2.7 7.0 ± 2.4
EPA 4.7 ± 1.3 1.6 ± 0.8 0.5 ± 0.2
DPA 2.6 ± 0.9 3.2 ± 1.2 2.1 ± 0.9
DHA 9.3 ± 3.3 3.5 ± 1.3 5.6 ± 2.2
* p < 0.001 for LA, AA & DHA in El Molo cfd all others.
Legend to table 3
N, number of subjects; TC = Total Cholesterol; TG, Triglycerides. LA, Linoleic
Acid; LNA, alpha Linolenic Acid; AA, Arachidonic Acid; EPA, Eicosapentaenoic
acid; DHA, docosahexaenoic acid. Values are the average ± SD. Adapted from ref.
(32): El Molo live on a lava desert which runs down to the eastern shore of Lake
Turkana, N. Kenya (48), The Bantu were Baganda and Bunyoro people of central
Uganda, The Europeans were living in East Africa mainly, Kampala Uganda (data
from 49). The slow conversion of linoleic to AA and α-linolenic to DHA is illustrated
in the equilibrium of the higher linoleic acid content of the plasma lipids and the lower
AA and DHA in the vegetarian and European plasmas compared to the fish eating
people where preformed AA and DHA is consumed in the duiet and appears as higher
levels in the plasma. Such data reflects the rate limitations of the conversion process
especially -6 desaturase which is involved twice in the synthesis of DHA (50). The
higher circulating levels of AA and DHA would favour their incorporation into the
developing brain where their incorporation is an order of magnitude greater than their
synthesis from precursors (51).
These unique conditions of the Rift Valley lake shores replicate the contrast in the high
mortality from vascular disease and high prevalence of mental disease amongst US and
Europeans versus the low risk of Japanese, Greenland and Inuit Indians living on a rich
fish and sea food diet (34 ). Similarly, comparison of fish eating populations in the
Faroes compared to their genetically similar mainland Denmark contemporaries, shows that
the high intake of fish and seafoods results in higher birthweights and a lower proportion
of preterm deliveries (35). The advantage of longer gestations is the greater exposure of
the fetus and its developing vascular system and brain, to the placental biomagnification of
AA and DHA (36). The conclusion is that land based diets led increasingly in this century
to cardiovascular disease being no. 1 killer in Western consumers which would have made
cerebrovascular expansion in utero difficult, and been incompatible with expansion of the
hominid brain.
Experimental support for the above case came in an unexpected result from studies on
diabetes by our colleagues, Professor Lucilla Poston and others at St Thomas’s Hospital
Medical School. Pregnant rats were subjected to high saturated fat diets similar to those
consumed in Western countries and blood vessel function tested in mothers and newborn
offspring. The results from small vessel myography described arterial dysfunction
specifically associated with the high, fat Western type diet. Vascular function tests on the
15 day old pups from mothers on the high (30%) fat diet exhibited reduced vascular
endothelium dependent relaxation to acetylcholine (ACh) with evidence of constrictor
responses to noradrenaline and the thromboxane mimetic U46619. The vascular
dysfunction was still observable at 120 days of age despite rearing on a normal diet. Thus
the high fat diet fed to the mother changed the intrauterine milieu which caused persistent
vascular dysfunction in the newborn animals without any genetic predisposition. Diabetes
imposed on the high fat diet made vascular function worse. Biochemical analysis of the
tissues from the control low fat and high saturated fat animals revealed the high fat diet
selectively depressed liver DHA of the pups. Here is experimental evidence of the negative
influence of land based animal fats fed to the mother on the next generation, emphasising
the importance of long term nutritional forces (37).
The question which arises from this discussion is what is so special about DHA? Why has
DHA been chosen so overwhelmingly for photoreceptor and synaptic membranes, despite
the availability of similar molecules which would be less difficult to obtain, and are less
vulnerable to oxidative damage (38,39)? In particular, what advantage does it convey
relative to the very closely related ω3 and ω6 DPAs, each of which differs from DHA only
in the absence of one double bond (between carbons 4 -5, and 19-20, respectively)?
As described above, Nature’s preference for DHA in the brain is strikingly demonstrated in
large land mammals, in which DPA is the dominant ω3 metabolite yet neural membranes
still retain the DHA-rich composition observed in other species (possibly at the expense of
gross brain size, since DHA is in such limited supply). Significant quantities of the ω6
form of DPA are observed only in situations of artificial ω3 deficiency, yet even here brain
membranes are resistant to decreases in their DHA levels. Nature is thus highly sensitive
to the slight difference between DHA and DPA molecules; the presence of DHA’s full
complement of six double bonds is for some reason an important priority in neural
What is the cause of such specificity in membrane composition? It is understood that
biological membranes, while always having the form of a fluid lipid bilayer, have detailed
distributions of lipid and protein molecules that reflect the interactions between lipids and
integral membrane proteins (40). It seems that the one missing double bond in DPA
species renders them unsuitable for whatever lipid-protein interaction favours DHA’s
inclusion in membranes of the brain.
Tight regulation of membrane lipid composition extends to differentiation between
polyunsaturated species. We recently investigated the relationship between DHA and AA
levels in plasma of red cell membranes of maternal and fetal blood samples. While these
studies revealed only a modest correlation in levels of the two PUFA species in plasma
choline phosphoglycerides (r=0.62, p<0.001, n=74), a strong positive correlation was
revealed between DHA and AA in the maternal red cell membrane (r=0.85, p<0.0001,
n=74), and a still tighter relationship in the red cells of preterm infants (r=0.88,
p<0.00005, n=24) (41). Bearing in mind the very different dietary origins of these two
PUFAs, such significant correlations indicate that some powerful mechanism exists to
regulate their relative abundances in the membrane.
It is possible that specific esterification processes could explain the correlations. The
ethanolamine (PE) and serine phosphoglycerides (PS) have the highest content of DHA.
In the brain there is an active base-exchange reaction for serine and ethanolamine. Other
ω3 fatty acids do not esterify easily with PE and PS. So specificity of composition could
be brought about by DHA-PS or DHA-PE formation. None-the-less the double bonds in
positions 4-5 and 19-20 would still have to be relevant for the esterification to explain why
the ω6 and ω3 DPAs might not match these conditions.
Nuclear magnetic resonance (NMR) and fluorescence studies have attempted to
differentiate the membrane properties conferred by PUFAs. In another paper (42), we
discuss some of the constraints of such approaches and review the results obtained to date.
Holte et al., (43) have conducted a thorough NMR investigation of the effects of
polyunsaturation on lipid acyl chain orientational order, which revealed significant changes
as the number of double bonds increased from one to three, but little difference as further
double bonds were introduced. Ehringer et al. (44) directly compared the effects of 18:3
and 22:6 on membrane physical properties, and observed considerably higher permeability
and perhaps vesicle fusability in the samples containing DHA.
In summary, a number of studies have been conducted on the physical effects of
polyunsaturation on membranes, in which DHA has been compared to a range of other
unsaturated chains having from one to five double bonds. Thus far, however, all
differences that have been measured have been matters of degree, and none provide a
compelling explanation for the striking specificity with which DHA is selected for
membranes of the eye and brain. In addition, to our knowledge no study has compared
DHA to either species of DPA to search for whatever property it is that causes neural
membranes to discriminate so clearly between these seemingly similar molecules. The
minimized energy structures presented here (see below) represent a preliminary step in this
Where, then, can we hope to find an explanation of DHA’s preferred status in neural
membranes? An obvious starting point is in protein-lipid interactions: some way in which
DHA favourably affects any of the myriad integral membrane proteins which are so
important to neural membrane function. Such an effect could conceivably involve either a
specific, molecular interaction between lipid and protein, or some modulation of bulk
properties of the bilayer which alters protein function. We believe that specific binding
interactions between lipid and protein molecules in a biological membrane are unlikely,
since the membrane’s fluid state means that individual lipid molecules will be undergoing
rapid translational diffusion within the bilayer, and thus will never be in prolonged contact
with any one protein. Furthermore, Brown’s studies (45) on the rod photoreceptor outer
segment membrane revealed that specific chemical-type interactions could not be the cause
of DHA’s established role in supporting rhodopsin function. It was found that full
rhodopsin efficiency could be obtained by substituting other lipid mixtures designed to
mimic the bulk mechanical properties of the physiological, DHA-rich membrane. This
gave rise to a model in which DHA’s role was to promote mechanical conditions in the
membrane suitable to stabilize certain critical conformational changes undergone by
rhodopsin in the course of photoactivation. These models do not fully reconstitute the
structure of the photoreceptor cell and its synaptic function, the ten thousand fold adaptive
capability of which is still unexplained. However, should this model be valid to
conditions in vivo it could potentially be extended to other G-protein systems elsewhere in
the CNS.
Applying this reasoning to the problem of distinguishing DHA from DPA, we must find a
way in which the difference of one double bond might have a large enough impact on some
bulk membrane property. The simulated structures shown in the figures are encouraging in
this respect, as they show considerable differences between the minimized energy
conformations of di-DHA PE and di-DPA PE (perhaps the first results which show a
difference of sufficient magnitude to account for Nature’s longstanding, clear
discrimination between the two). It must be stated, though, that these simulations have
been carried out in vacuum and report only the lowest energy state; their applicability to
lipid molecules in a fluid bilayer at physiological temperatures is thus open to question.
A more speculative, possibility is that DHA in vivo plays a more direct role in
neuronal signalling, in which some special properties conferred on the membrane
by DHA chains exert an influence on membrane electrical phenomena. These might
include distinctive dielectric or polarizability properties arising from the unique
periodic and symmetric arrangement of double bonds in the DHA chain (which
would be disrupted in DPAs). It is conceivable that some polarization of π-electron
clouds might occur, and perhaps even be transmitted from one double bond to
another (either within a given chain, or between neighbouring chains in the
membrane). It must be emphasized that this model is strictly speculative, and there
is no evidence, experimental or theoretical, to support it. An experiment to measure
the dielectric response of lipid systems at a broad range of applied frequencies is
currently being developed. In a similar vein, Penrose (46) has postulated that some
brain functionality may arise due to quantum coherence in the microtubules of
neurones (46); it may be worthwhile to look for a similar phenomenon in
membranes containing DHA.
Legend to figures:
Global three dimensional energy minimized structures of DHA, n-3 DPA, n-6 DPA and
various phospholipids containing these LC-PUFA were constructed with MOPAC
software (Alchemy 2000 v. 2.0, Tripos Inc., St. Louis, MO). MOPAC (molecular orbital
pacakage) which calculates the steric energy and energy minimized configuration of a given
molecule by successive approximation, and is considered to be reasonably accurate as
compared to known structures. The free fatty acids (FFA) DHA, n-3 DPA, n-6 DPA are
shown in Figures 1 to 3, respectively. The sixth ethylenic bond in DHA changes the
character of the FFA, completing the methylene interupted sequence along the carbon
chain, and conferring a folded, slightly spiral nature to the molecule. In n-3 DPA, the side
of the chain closest to the terminal methyl is essentially ethylenic, while the other side is
essentially saturated. The opposite is seen in the n-6 DPA, where the side of the chain
closest to the methyl group is saturated, and the other side unsaturated. The DPAs lack the
full methylene interupted sequence of double bonds throughout the carbon chain, which
could be the basis of why they apparently do not have the functionality required by retinal
and brain tissue.
The energy minimized ethanolaminephosphoglyceride structures with DHA (Fig. 4)
and n-3 DPA (Fig. 5) dramatically illustrated the significance of the missing double bond in
DPA vs. DHA. The final (C19) double bond in DHA constrains the position of the
phosphoethanolamine head group, pulling it in and maintaining the spiral structure. This
reduces the molecular volume, and may facilitate communication between the head group
and the esterfied lipid chains. In contrast, the head group in n-3 DPA is far less
constrained, and in fact moves away from the lipid ester chains. This structure would be
more typical of phospholipids in general since most FA are less polyunsaturated than
DHA. The cell membrane is in constant fluid motion so these structures only represent the
preferred orientations of the molecules.x
Figure 1: 3D energy-minimized structure of docosahexaenoic acid (DHA). This and
following figures energy minimized and drawn with MOPAC as described in text.
Figure 2: N-3 docosapentaenoic acid (n-3 DPA).
Figure 3: N-6 docosapentaenoic acid (n-6 DPA).
a b
Figure 4: a: 3D energy-minimized structure of phospholipid with ethanolamine,
DHA, DHA. Side view. b: Ethanolamine, DHA, DHA. End view, note position of
phosphate group.
Figure 5a: a: 3D energy-minimized structure of phospholipid with ethanolamine, n-3
DPA, n-3 DPA. Side view. b: Ethanolamine, n-3 DPA, n-3 DPA. End view, note
position of phosphate group.
There is much still to be learned about the physical properties of membranes containing
DHA. The extremely high degree of specificity with which it is selected for membranes of
the brain (and has been, since very early evolutionary times) cannot be explained on the
basis of the conventional measurements that have been made thus far. DHA’s special role
may relate either to undefined interactions with integral membrane proteins or, more
speculatively, to some role in neuronal signalling arising from unusual electrical properties.
Nature’s sharp discrimination between DHA and the nearly identical DPA species may give
guidance to further inquiries into DHA’s putative role, by focusing attention on the
importance of the full complement of six periodic double bonds.
We are grateful for financial support from the Mother and Child Foundation and Martek
Biosciences especially for travel expenses for meetings to finalise this paper.
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... Indeed, it was reported that among different tissues, the teleost brain possesses the highest expression of fads2, and this enriched pattern of expression in marine fish brain serves to retain a local, functional Δ6 desaturase to ensure a sufficient supply of DHAs to neural tissues (Monroig et al. 2018). The enhanced biosynthesis of DHAs was particularly evident for the TeO region of the surface fish's brain, which may be related to the essential roles of DHAs in facilitating advanced functions of photoreceptors in the eye (Crawford et al. 1999). In addition to augmented local biosynthesis of DHAs, increased incorporation of DHAs into membrane phospholipids via remodeling processes were also evident in the brain. ...
... Similarly in human cohorts, increased maternal DHA intake from seafood consumption was positively associated with improvements in prosocial behavior and fine motor skills of their children (Hibbeln et al. 2007). The loss of DHA-enriched neural domains might also be partly explained by vision loss in cavefish driven by an environment of total darkness, since DHA represents the PUFA uniquely utilized by photoreceptors (Crawford et al. 1999). We then validated via qRT-PCR that the specific reductions in membrane DHAs in the brain of cavefish were attributed to reduction in DHA biosynthetic capacity via fads2 along the Δ4 desaturase pathway ( fig. ...
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The Sinocyclocheilus represents a rare, freshwater teleost genus endemic to China that comprises the river-dwelling surface fish and the cave-dwelling cavefish. Using a combinatorial approach of quantitative lipidomics and mass-spectrometry imaging (MSI), we demonstrated that neural compartmentalization of lipid distribution and lipid metabolism are associated with the evolution of troglomorphic traits in Sinocyclocheilus. Attenuated DHA biosynthesis via the Δ4 desaturase pathway led to reductions in docosahexaenoic acid (DHA)-phospholipids in cavefish cerebellum. Instead, cavefish accumulates arachidonic acid (ARA)-phospholipids that may disfavor retinotectal arbor growth. Importantly, MSI of sulfatides, coupled with immunostaining of myelin basic protein and transmission electron microscopy images of hindbrain axons revealed demyelination in cavefish raphe serotonergic neurons. Demyelination in cavefish parallels the loss of neuroplasticity governing social behavior such as aggressive dominance. Outside the brain, quantitative lipidomics and qRT-PCR revealed systemic reductions in membrane esterified DHAs in the liver, attributed to suppression of genes along the Sprecher pathway (elovl2, elovl5, acox1). Development of fatty livers was observed in cavefish, likely mediated by an impeded mobilization of storage lipids, as evident in the diminished expressions of pnpla2, lipea, lipeb, dagla and mgll; and suppressed β-oxidation of fatty acyls via both mitochondria and peroxisomes, reflected in the reduced expressions of cpt1ab, hadhaa, cpt2, decr1 and acox1. These neurological and systemic metabolic adaptations serve to reduce energy expenditure, forming the basis of recessive evolution that eliminates non-essential morphological and behavioral traits, giving cavefish a selective advantage to thrive in caves where proper resource allocation becomes a major determinant of survival.
... Une fois ingérés, les lipides sont hydrolysés en AG libres non estérifiés (Figure 21) (Bozek et al. 2015;Crawford et al. 1999). En effet, chez les primates, les niveaux de lipides cérébraux enrichis tendent à évoluer quatre fois plus vite que dans les autres tissus mais cela varie également selon la région cérébrale étudiée. ...
Les troubles du spectre autistique (TSA) sont des troubles neurodéveloppementaux, touchant 3,7 hommes pour 1 femme en France, qui se traduisent principalement par des déficits persistants dans les comportements sociaux ainsi que par des comportements, intérêts et activités restreints et répétés. L’exposition à des facteurs environnementaux, notamment durant la période périnatale, serait majoritairement impliquée dans l’étiologie des TSA. On retrouve parmi ces facteurs, des composés pharmacologiques comme l’acide valproïque (VPA) (Dépakine®), dont l’exposition in utero augmente la probabilité de développer des TSA. Le cervelet, par ses fonctions cognitives et motrices, représente l’une des structures les plus impliquées dans la physiopathologie des TSA par des modifications anatomiques, cellulaires et moléculaires chez des patients et modèles animaux de TSA. Une supplémentation en acides gras polyinsaturés à longue chaîne n-3 (AGPI-LC n-3) sur plusieurs mois permet de réduire les symptômes de TSA chez des enfants. L’objectif de cette thèse a donc été de déterminer si une alimentation supplémentée en AGPI-LC n-3 en période périnatale pouvait protéger des symptômes de TSA induits par une exposition in utero au VPA chez la souris. Nous avons réalisé une étude longitudinale portant sur l’évolution des symptômes sociaux et moteurs ainsi que sur les corrélats cellulaires et moléculaires cérébelleux chez des souris mâles et femelles. Ces travaux ont permis de mettre en évidence qu’une alimentation équilibrée en AGPI n-3 et n-6 permet de protéger contre l’apparition de symptômes comportementaux, la perte de neurones cérébelleux et la dysbiose du microbiote intestinal.
... That 'optimal' diet, as part of 'environment' (nurture), is the one that has driven our current physiology (nature) and is increasingly considered to be a diet that was available to us at the seashore. The still dominant but incorrect hypothesis, of our derivation from the savannah is unlikely for many reasons, e.g., because of the lack of local fossils, the daily needed large amounts of water and sodium to prevent dehydration in a hot climate, and the lack of advantage to hunt in an open plain with a relatively slow moving body in an upright position [161][162][163][164][165]. But also because of the scarcity of iodine, both the scarcity and abundance of selenium in many places on the land, and our poor ability to synthesize the fish oil fatty acids EPA and DHA from their precursor essential fatty acid alpha-linolenic acid that is abundantly present in terrestrial plants [164,[166][167][168]. ...
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Iodide is an antioxidant, oxidant and thyroid hormone constituent. Selenoproteins are needed for triiodothyronine synthesis, its deactivation and iodine release. They also protect thyroidal and extrathyroidal tissues from hydrogen peroxide used in the ‘peroxidase partner system’. This system produces thyroid hormone and reactive iodine in exocrine glands to kill microbes. Exocrine glands recycle iodine and with high urinary clearance require constant dietary supply, unlike the thyroid. Disbalanced iodine-selenium explains relations between thyroid autoimmune disease (TAD) and cancer of thyroid and exocrine organs, notably stomach, breast, and prostate. Seafood is iodine unconstrained, but selenium constrained. Terrestrial food contains little iodine while selenium ranges from highly deficient to highly toxic. Iodine vs. TAD is U-shaped, but only low selenium relates to TAD. Oxidative stress from low selenium, and infection from disbalanced iodine-selenium, may generate cancer of thyroid and exocrine glands. Traditional Japanese diet resembles our ancient seashore-based diet and relates to aforementioned diseases. Adequate iodine might be in the milligram range but is toxic at low selenium. Optimal selenoprotein-P at 105 µg selenium/day agrees with Japanese intakes. Selenium upper limit may remain at 300–400 µg/day. Seafood combines iodine, selenium and other critical nutrients. It brings us back to the seashore diet that made us what we currently still are.
... As stated above, it is now believed by some that the importance of marine resources for early modern humans reside at least on the fact there are crucial nutritional elements for human health, specifically for the development of the brain and the retinal organs. These elements are omega 3 and omega 6, long-chain polyunsaturated fatty acids, such as the Docosahexaenoic acid (DHA) and Arachidonic acid (AA) (Crawford et al., 1999;Parkington 2001;Broadhurst et al., 2002;Langdon 2006;Uauy and Dangour 2006;Carlson and Kingston 2007;Cunnane et al., 2007). These fatty acids, also invaluable during pregnancy and early childhood, are not produced in the human body (Broadhurst et al., 2002;Jensen 2006;Milligan and Bazinet 2008) but occur naturally in aquatic plants and animals, if not exclusively, at least frequently in higher concentrations than in terrestrial food elements. ...
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Coastal prehistoric hunter-gatherers in Atlantic Iberia were particularly important to understanding Paleolithic human innovation and resilience. This study will focus on Middle and Upper Paleolithic adaptations to the Iberian Atlantic border. Elements such as intensity and diversity of marine foods, site location, distance to shore, submerged platform, and bathymetry are discussed for the region between Gibraltar and the Gulf of Biscay.
This datasheet on Aquatic organisms as human food covers Identity, Description, Further Information.
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Docosahexaenoic acid-containing lysophosphatidylcholine (DHA-LysoPC) is presented as the main transporter of DHA from blood plasma to the brain. This is related to the major facilitator superfamily domain-containing protein 2A (Mfsd2a) symporter expression in the blood–brain barrier that recognizes the various lyso-phospholipids that have choline in their polar head. In order to stabilize the DHA moiety at the sn-2 position of LysoPC, the sn-1 position was esterified by the shortest acetyl chain, creating the structural phospholipid 1-acetyl,2-docosahexaenoyl-glycerophosphocholine (AceDoPC). This small structure modification allows the maintaining of the preferential brain uptake of DHA over non-esterified DHA. Additional properties were found for AceDoPC, such as antioxidant properties, especially due to the aspirin-like acetyl moiety, as well as the capacity to generate acetylcholine in response to the phospholipase D cleavage of the polar head. Esterification of DHA within DHA-LysoPC or AceDoPC could elicit more potent neuroprotective effects against neurological diseases.
Living in a Dangerous Climate provides a journey through human and Earth history, showing how a changing climate has affected human evolution and society. Is it possible for humanity to evolve quickly, or is slow, gradual, genetic evolution the only way we change? Why did all other Homo species go extinct while Homo sapiens became dominant? How did agriculture, domestication and the use of fossil fuels affect humanity's growing dominance? Do today's dominant societies – devoted as they are to Darwinism and 'survival of the fittest' – contribute to our current failure to meet the hazards of a dangerous climate? Unique and thought provoking, the book links scientific knowledge and perspectives of evolution, climate change and economics in a way that is accessible and exciting for the general reader. The book is also valuable for courses on climate change, human evolution and environmental science.
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A hypothesis as to the abiotic emergence in hydrothermal surface systems, of a zeolite supported reproducible proto-RNA, selecting for, and on desiccation condensing, the selected specific amino acids into replicable proteins, the zeolite tubules acting as exoskeletons for RNA stacks. Initial cells were likely protected from surface incident UVC by silicate 'shells' lined with lipid and or 'polysaccheride membranes, initially informal sheet-layers overlying stromatolite type structures, evolving into protective cell-shells. UVC protection, including by oxygenation of the atmosphere, allowed the lipid / polysaccheride membrane linings of UVC protective shells, to evolve to become stand alone membrane systems. These processes might be universal in the origin of life, and determined by the properties of the universe.
Over the years, the scientific community has sought improvements in the life quality of patients diagnosed with Alzheimer's disease (AD). Synaptic loss and neuronal death observed in the regions responsible for cognitive functions represent an irreversible progressive disease that is clinically characterized by impaired cognitive and functional abilities, along with behavioral symptoms. Currently, image and body fluid biomarkers can provide early dementia diagnostic, being it the best way to slow the disease's progression. The first signs of AD development are still complex, the existence of individual genetic and phenotypic characteristics about the disease makes it difficult to standardize studies on the subject. The answer seems to be related between Aβ and tau proteins. Aβ deposition in the medial parietal cortex appears to be the initial stage of AD, but it does not have a strong correlation with neurodegeneration. The strongest link between symptoms occurs with tau aggregation, which antecede Aβ deposits in the medial temporal lobe, however, the protein can be found in cognitively healthy older people. The answer to the question may lie in some catalytic effect between both proteins. Amid so many doubts, Aducanumab was approved, which raised controversies and results intense debate in the scientific field. Abnormal singling of some blood biomarkers produced by adipocytes under high lipogenesis, such as TNFα, leptin, and interleukin-6, demonstrate to be linked to neuroinflammation worsens, diabetes, and also severe cases of COVID-19, howsoever, under higher lipolysis, seem to have therapeutic anti-inflammatory effects in the brain, which has increasingly contributed to the understanding of AD. In addition, the relationship of severe clinical complications caused by Sars-CoV-2 viral infection and AD, go beyond the term “risk group” and may be related to the development of dementia long-term. Thus, this review summarized the current emerging pharmacotherapies, alternative treatments, and nanotechnology applied in clinical trials, discussing relevant points that may contribute to a more accurate look.
Extensive variation in life-history patterns is documented across primate species. Variables included are gestation length, neonatal weight, litter size, age at weaning, age at sexual maturity, age at first breeding, longevity, and length of the estrous cycle. Species within genera and genera within subfamilies tend to be very similar on most measures, and about 85% of the variation remains when the subfamily is used as the level for statistical analysis. Variation in most life-history measures is highly correlated with variation in body size, and differences in body size are associated with differences in behavior and ecology. Allometric relationships between life-history variables and adult body weight are described; subfamily deviations from best-fit lines do not reveal strong correlations with behavior or ecology. However, for their body size, some subfamilies show consistently fast development across life-history stages while others are characteristically slow. One exception to the tendency for relative values to be positively correlated is brain growth: those primates with relatively large brains at birth have relatively less postnatal brain growth. Humans are a notable exception, with large brains at birth and high postnatal brain growth.
Foreword Malcolm Longair; 1. Space-time and cosmology Roger Penrose; 2. The mysteries of quantum physics Roger Penrose; 3. Physics and the mind Roger Penrose; 4. On mentality, quantum mechanics and the actualization of potentialities Abner Shimony; 5. Why physics? Nancy Cartwright; 6. The objections of an unashamed reductionist Stephen Hawking; 7. Response Roger Penrose; Appendix I: Goodstein's theorm and mathematical thinking; Appendix II: Experiments to test gravitationally induced state reduction.
The Middle Stone Age (MSA) asociated hominids from Klasies River Mouth (KRM) have taken on a key role in debate about the origins of modern humans, with their craniofacial remains seen as either representing the earliest well-dated modern humans in southern Africa or orthognathic late archaic humans. Diagnostic postcranial remains from Klasies are few, but one specimen—a proximal right ulna from the lower SAS member—is useful for assessing the morphological affinities of these hominids. Canonical variates analysis using 14 proximal ulnar dimensions and comparative data from European, west Asian and African archaic humans, and Levantine Mousterian, European Upper Paleolithic, African Epipaleolithic and diverse recent modern human samples (many of recent African descent) were employed to assess the morphological affinities of this specimen. Results suggest an archaic total morphological pattern for the Klasies ulna. Analysis of diaphyseal cross-sectional geometry reveals an ulnar shaft with relatively thick cortical bone, but the specimen cannot be readily distinguished from Neandertals or early anatomically modern humans on the basis of shaft cross-sectional properties. If the isolated ulna from Klasies is indicative of the general postcranial morphology of these hominids, then the MSA-associated humans from KRM may not be as modern as has been claimed from the craniofacial material. It is possible also that the skeletal material from KRM reflects mosaic evolution—retention of archaic postcranial characteristics, perhaps indicating retention of archaic habitual behavior patterns, in hominids that were becoming craniofacially modern.
The fragmentary hominid humerus shaft discovered at Border Cave in 1987 can be studied from several perspectives. A small flake of cortical bone yields histological evidence for an age at death late in the fifth decade, plus relatively small osteons (total osteon area). Shaft dimensions, cross-sectional characteristics at midshaft and estimated length are compared with values from Late PleistoceneHomo sapiensand to humeri from the Later Stone Age in South Africa (C14 dated 2090–9750BP). The Border Cave humerus is platybrachic, has a %CA (cortical area/total area×100) of 82·7 at midshaft, and is estimated to have been about 330mm in length, or less. It is morphologically most similar to Neanderthal humeri, suggesting that it is “archaic”. Its robustness and its small osteons are consistent with Middle Stone Age antiquity. Some features suggest that it may represent a larger, more robust version of the Later Stone Age population. This in turn suggests possible continuity from archaic to modern infracranial anatomy in southern Africa.
The temporal association of hominid evolution with a period of global climatic instability and cooling is suggestive of a causal relationship. A number of authors have proposed a climatic forcing model for the timing and nature of evolutionary changes in human evolution during the Pliocene and Pleistocene (5-3 Mya), such as the appearance of new taxa, and by inference only a limited role for continuous evolutionary change in response to inter- and intra-specific competition at the local level. A major problem with such models is that both climatic change and hominid evolution are now recognised as complex with numerous events. By splitting climatic change as revealed in deep sea cores into a number of distinct attributes (temperature, stability and variability) and examining the relationship of each to the appearance, diversity and disappearance of hominid taxa it is possible to investigate more closely the effect of climatic change on hominid evolution. It is shown that the effect of climatic change can be observed in relation to extinction events, but that there is no significant relationship with the first appearance of hominid taxa. This implies that the mechanism by which climate influences evolution is primarily through extinction, and that further factors dependent upon local competitive conditions play a significant part in the appearance of new taxa.
Extensive variation in life-history patterns is documented across primate species. Variables included are gestation length, neonatal weight, litter size, age at weaning, age at sexual maturity, age at first breeding, longevity, and length of the estrous cycle. Species within genera and genera within subfamilies tend to be very similar on most measures, and about 85% of the variation remains when the subfamily is used as the level for statistical analysis. Variation in most life-history measures is highly correlated with variation in body size, and differences in body size are associated with differences in behavior and ecology. Allometric relationships between life-history variables and adult body weight are described; subfamily deviations from best-fit lines do not reveal strong correlations with behavior or ecology. However, for their body size, some subfamilies show consistently fast development across life-history stages while others are characteristically slow. One exception to the tendency for relative values to be positively correlated is brain growth: those primates with relatively large brains at birth have relatively less postnatal brain growth. Humans are a notable exception, with large brains at birth and high postnatal brain growth.