Invited Review

J Nutrigenet Nutrigenomics 2009;2:91–102 Published online: July 10, 2009

DOI: 10.1159/000228251

Nutrigenetics in the Light of Human

Evolution1
Fabio Verginelli a Federica Aru a Pasquale Battista b Renato Mariani-Costantini a
Departments of a Oncology and Neuroscience, Section of Molecular Pathology, and b Human Movement Sciences,
G. d’Annunzio University, and Center of Excellence on Aging (Ce.S.I.), G. d’Annunzio University Foundation,
Chieti, Italy

Key Words lection of genetic variants that allowed better utilization of

Culture ⴢ Diet ⴢ Disease ⴢ Encephalization ⴢ Genetics ⴢ new foods, different in relation to geography and culture.
Human evolution ⴢ Metabolism Today population growth, globalization and economic pres-
sure powerfully affect diets worldwide. We must take into
account our evolutionary past to meet the present nutrition-
Abstract al challenges. Copyright © 2009 S. Karger AG, Basel
Bio-cultural adaptations to new foods played a key role in
human evolution. The fossil record and sequence differenc-
es between human and chimpanzee genes point to a major
dietary shift at the stem of human evolution. The earliest Diet and Human Evolution
representatives of the human lineage diverged from the an-
cestors of chimpanzees because of their better adaptation To quote the title of a commentary by Theodosius Dob-
to hard and abrasive foods. Bipedalism and modifications of zhansky: ‘Nothing in biology makes sense except in the
the hand, which allowed tool manufacture and use, impact- light of evolution’ [1, 2]. Evolutionary success depends on
ed on dietary flexibility, facilitating access to foods of animal the ability to adapt to environmental change. As explained
origin. This promoted major anatomic, physiologic and met- by Darwin in On the Origin of Species (1859): ‘It is not the
abolic adaptations. Encephalization, which requires high- strongest of the species that survive, nor the most intelli-
quality diet, characterizes the evolutionary sequence that, gent, but the one most responsive to change’ [3, 4]. Food
through the Homo ergaster/erectus stages, led to our species, is crucial to survival. Thus the ability to meet nutritional
Homo sapiens, which originated in Africa about 200,000 requirements by adapting to new foods plays a crucial role
years ago. At the end of the Ice Age, climatic changes and in the origin and evolution of species. Darwin’s ‘finches’
human impact determined a major food crisis, which trig- (Geospizinae) on the Galapagos islands provide a classic
gered the agricultural revolution. This affected nutrition and model for this concept, as the diversification between re-
health, with rapid evolutionary adaptations through the se- lated species of these passerine birds is readily evident

Presented at the Second Congress of the International Society of

Nutrigenetics/Nutrigenomics (ISNN), October 6–8, 2008, Geneva,
1 Dedicated to the bicentennial of Charles Robert Darwin. Switzerland.
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© 2009 S. Karger AG, Basel Renato Mariani-Costantini

1661–6499/09/0022–0091$26.00/0 Unit of Molecular Pathology and Genomics, Center of Excellence on Aging (Ce.S.I.)
Fax +41 61 306 12 34 ‘G. d’Annunzio’ University Foundation, Via Colle dell’Ara
E-Mail [email protected] Accessible online at: IT–66013 Chieti (Italy)
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www.karger.com www.karger.com/jnn Tel. +39 0871 541 496, Fax +39 0871 541 495, E-Mail [email protected]
 thropological data indicate that between 5 and 10 mil-
lion years ago (mya), the lineage of our extinct bipedal
ancestors diverged from the most closely related ape lin-
eage, that led to the two extant chimpanzees, Pan troglo-
dytes, the common chimpanzee, and Pan paniscus, the
‘bonobo’ [9]. This critical split of the common hominoid
root followed climatic and geological events that, in east
Africa, led to an expansion of dryer, sparsely wooded sa-
vannahs at the expense of primary rainforest [10]. This
must have resulted in increased availability of potential
new foods that had previously been scarcely exploited,
such as hard seeds, insects and abrasive roots and grass-
es, with comparatively reduced availability of fruits and
soft leaves. The hominoid species ancestral to both hu-
mans and chimpanzees, which occupied these progres-
Fig. 1. Darwin’s ‘finches’ (also known as the Galápagos Finches or sively fragmented forest environments and was most
Geospizinae), a classic example of diversification by natural selec- probably partially adapted to terrestrial life, must have
tion, from the original illustration published in the 1859 and sub- been subjected to a strong selective pressure for new nu-
sequent editions of On the Origin of Species [3]. These Passerine tritional adaptations. In fact, the earliest known fossils
birds include a number of related species, mostly classified with-
ascribed to close relatives or direct ancestors of humans,
in the genus Geospiza, which are connected to American tanagers
in the family Emberizidae rather than to the European finches. broadly dated between 7 and 3 mya, had chimpanzee-
(1) Geospiza magnirostris. (2) Geospiza fortis. (3) Geospiza par- sized brains and may have been still imperfectly bipedal,
vula. (4) Certhidea olivacea. G. magnirostris and G. fortis have but already displayed notable and typical morphological
broad, deep beaks useful for crushing seeds; G. parvula has a and structural changes in the dentition (decreased size
small symmetrical beak, suitable to more generalist ground feed-
of canines, large molars and, particularly, increased
ing, while C. olivacea, the ‘warbler’ finch, has an elongated beak
useful for capturing insects. In September 1839, when HMS Bea- thickness and different microstructure of enamel) [11,
gle reached the Galápagos islands, these and other ‘finches’ struck 12]. These dental changes allowed a functional shift from
Darwin’s mind, later highlighting the concept that exploitation of ape-like slicing and cutting, suited to relatively soft but
different food resources leads to evolutionary divergence. It has tough foods and dependent on shearing crests forming
been recently shown that beak diversification in Geospiza and
on molars at wear-exposed enamel-dentine junctions, to
other bird species is determined by heterochronic and heterotop-
ic gene regulation during craniofacial development. human puncture-crushing and grinding, better adapted
to process hard, brittle foods and affording better protec-
tion, and thus prolonged tooth life, in the presence of an
abrasive diet. This provided a critical selective advantage
from beak morphologies, which manifest different nutri- since, under natural conditions, the health and lifespan
tional adaptations (fig. 1) [3]. Today we know that in bird of mammals is primarily dependent on the status of the
species, beak diversification is determined by the heter- dentition, which must allow adequate food processing
ochronic and heterotopic expression of genes differential- and protection from infection [13]. Genome-wide pro-
ly modulated during craniofacial morphogenesis, partic- tein sequence evolution data support the view that di-
ularly BMP4 (implicated in the well-known signaling etary shifts played a major role in the divergence between
pathway of bone morphogenetic proteins) and calmodu- the ancestors of humans and chimpanzees. In fact, based
lin (a mediator of calcium signaling) [5–7]. Notably, a re- on the comparison of 7,645 human-chimp-mouse gene
cent study conducted on a population of common Medi- trios, the most significant functional gene categories
terranean lizards (Podarcis sicula), which had been exper- showing positive selection include those involved in
imentally introduced into a novel insular environment, amino acid metabolism, in addition to those implicated
demonstrated that exploitation of a different dietary re- in skeletal regulation, olfaction and sound perception
source may trigger surprisingly rapid large-scale evolu- [14]. Furthermore, the promoter sequences and the ami-
tionary divergence in morphology and physiology [8]. no acid sequences of diet-related genes carry more dif-
The fossil record points to a major dietary shift at or ferences between humans and chimpanzees than do ran-
near the stem of human evolution. Genetic and paleoan- dom genes [15].
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 a b c

Fig. 2. Lower Paleolithic flake tool from the Saharan desert, rep- breaks with sharp edges. a Dorsal (upper) face of the flake.
resentative of stone industries associated with Homo erectus. This b Sharp edges suitable for cutting and slicing meat and skin.
flake was struck with a stone hammer from a nucleus of chert, c Ventral (or underside) face, with the characteristic percussion
which like other cryptocrystalline stones used by our ancestors, bulb starting from the striking platform.

Biocultural Factors and Dietary Adaptations in ticularly defleshed marrowbones and heads containing
Earliest Human Ancestors brains, abandoned by carnivores, as well as placentas,
which are shed in numbers during delivery seasons, must
In the human lineage, technology was soon to become have been readily available on the ancient African savan-
a major motor for new nutritional adaptations. Several nahs densely populated by large herding ungulates [21].
species of extant Old and New World primates may use The bipedal gait also freed hands and arms from their
stone anvils and hammers to process hard foods, such as function in locomotion, allowing their full use to hold
nuts, but in general the upper limbs of non-human pri- excess food, which could then be carried away in quan-
mates are anatomically unsuited to manufacture and use tity to safe hiding places (fig. 3). This must have signifi-
tools with sufficient precision [16]. Instead, in the early cantly improved the scavenging strategies of our early an-
representatives of our lineage, the extensive anatomical cestors, since carrion in open savannahs rapidly attracts
remodeling of the hand made possible by the progressive dangerous competitors and thus cannot be consumed on
acquisition of bipedalism, perfected the acquisition of the site [22].
two fundamental human handgrips – the ‘power’ and Abundant archaeological evidence supports the view
‘precision’ grips – which serve for finely controlled crush- that the use of stone tools allowed dietary flexibility and
ing, for the related ability to manufacture sharply-edged a more systematic reliance on animal foods in the spe-
stone tools (fig. 2), and for the use of such tools in cutting cific lineage of early bipedal apes that gave rise to the ge-
and slicing [17]. These critical abilities decisively facili- nus Homo [23]. The first evidence of stone tools use for
tated access to foods of animal origin, in the absence of bone defleshing and crushing, from a site in Gona in the
the specific dental adaptations usually associated with Afar region of Ethiopia, is dated at 2.6 mya [24]. The in-
mammalian carnivorism [18–20]. Animal carcasses, par- creased dietary quality due to tool use may have deter-
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 Color version available online
a b

Fig. 3. Several extant chimpanzee populations live in environ- area, the ability to walk upright, using both arms and hands, in
ments that may approach that of the ancient common ancestor of addition to the mouth, to carry away potential food items for lat-
humans and chimpanzees. a A band of common chimpanzees er consumption under cover, provides a distinct advantage. The
(Pan troglodytes) feeding at the edge of a forested area in Uganda. young male (b), a member of the band in a, exemplifies this type
When food is abundant and not specifically concentrated, the of behavior, which must have been useful to our earliest ancestors
feeding behavior is relaxed and animals use only the 4-legged gait. in competing with other scavengers for placentas or partial ani-
However, when a cache of food is concentrated in a limited open mal carcasses. Images: R. Mariani-Costantini (2005).

mined rapid large-scale evolutionary divergences in mor- dated between 1.8 and 1.0 mya, are found in a broad
phology, physiology, social behavior and ecology. In par- southern Eurasian belt comprising sites as distant as
ticular, it resulted in larger body size, and may have Dmanisi in Georgia, Sangiran in Java and Atapuerca in
promoted the acquisition of a set of diet-related anatom- Spain [29, 30].
ic, physiologic and metabolic characteristics which dis- Significantly, the spread of H. ergaster/erectus coincid-
tinguish humans from the extant great apes. These in- ed with the extinction of the robust Australopithecines,
clude encephalization, decrease in gastrointestinal tract African bipedal apes representing a side-branch of the
length, better adaptations to diets high in fat and choles- human lineage that did not develop stone tool technology
terol and related changes in gut microbiota [25–27]. and that may have subsisted mainly on vegetable savan-
nah foods (fig. 4) [9, 12].
Archaeological evidence at most H. erectus sites, both
Meat, Stones, Fire and the Spread of the Homo in Africa and in Eurasia, strongly suggests that this hom-
ergaster/erectus Lineage inin species was capable of hunting large mammals or, at
least, successfully competing with large carnivores for
Progressive incorporation of more meat into the diet the appropriation of carrion [30]. The consistent evidence
of our early ancestors depended on progress in active of cannibalism associated with the Eurasian forms de-
hunting in addition to scavenging, in both cases made rived from H. erectus along the extinct antecessor/heidel-
possible by improvements in tool technology and social bergensis/neanderthalesis lineage and also, later, along
organization (fig. 4). Ecologically, carnivores, particular- our own lineage, H. sapiens, suggests that dependence on
ly those of large size which are more mobile and can adapt meat was driven by ecological necessity [31–37].
to different temperatures, tend to have a wide geographic As stated above, human evolution provides a fascinat-
dispersal, as meat can be naturally found in a large vari- ingly complex model for the study of the evolutionary
ety of climates and habitats [28]. Thus, increased car- relevance of biocultural interactions. Control of fire was
nivorism may lie at the basis of the first wave of the early a cultural adaptation that impacted on dietary quality,
human ‘out of Africa’ migration, which appears to have and hence on biology [38]. Data from extant apes suggest
coincided with the emergence of the large-sized Homo an innate preference for cooked food in hominoids [39].
ergaster/erectus lineage in east Africa around 1.9 mya, The earliest evidence of fire use, probably due to H. ergas-
and soon after in Eurasia. The first non-African fossils, ter/erectus, comes from archaeological sites in eastern
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 H. neanderthalensis H. sapiens
(1,400 cc) (1,350 cc)
0 H. ergaster/erectus
(900 cc)

1 A. aethiopicus A. robustus
(410 cc) (530 cc)

H. habilis
A. boisei (600 cc)
(510 cc) H. antecessor/heidelbergensis
2 (1,000 cc)
A. africanus
(415 cc)

3 A. afarensis
(385 cc)
MYA

A. anamensis
4
A. ramidus

O. tugenensis

6 S. tchadensis
(350 cc)

Fig. 4. Evolutionary timetable of fossil hominins and brain sizes. pedal ape species dated between 3 and 1 mya, such as Australo-
The first fossil species, Sahelanthropus tchadensis, represented by pithecus robustus, Australopithecus boisei and Australopithecus
a unique well-preserved skull dated to about 7 mya, was probably aethiopicus, did not develop particularly large brains. These ex-
very close to the common ancestor of humans and chimpanzees, tinct close relatives of humans did not develop a distinct stone tool
had a cranial capacity of about 350 cm3 (that of chimpanzees), but technology and appear to have relied on a diet of grubs and plants.
dental features supporting its relation with the human lineage. Returning to the human lineage, about 2 mya, with the emergence
Orrorin tugenensis, Ardipithecus ramidus and Australopithecus of Homo ergaster/erectus, probably from Homo habilis or related
anamensis, dated between about 6.5 and 4 mya, had dental adap- forms, there is a rapid increase in absolute and relative brain size,
tations typical of the human lineage and postcranial anatomy in- associated with strong evidence of tool manufacture and use. H.
dicating imperfect bipedalism. Brain size was most probably in ergaster/erectus butchered, and probably hunted, large animals.
the chimpanzee range, although informative fossils are lacking. Reliance on meat increased environmental adaptability, allowing
In Australopithecus afarensis, a later bipedal ape dated at about 3 spread to Eurasia, where local evolution took place along the an-
mya, and represented by the famous partial skeleton known as tecessor/heidelbergensis/neanderthalensis lineage. These ancient
‘Lucy’, we have evidence of a cranial capacity still nearing that of Eurasian hominids, which appear to have been later entirely re-
chimpanzees. With Australopithecus africanus, and particularly placed by Homo sapiens, certainly relied on meat and more or less
with Homo habilis, there is a definite increase in brain size. The consistently used fire. H. sapiens, our species, emerged about
available documentation suggests that these species tended to 200,000 years ago from an advanced African H. ergaster/erectus
consume animal foods, possibly by scavenging, although tool use population. The brain of H. sapiens, although on average smaller
is not clearly documented. Notably, the robust australopithecines, than that of Neanderthals, shows major structural differences,
representing a side branch of the human tree which includes bi- particularly expansion of the frontoparietal regions.
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and southern Africa, such as Lake Baringo, Koobi Fora males, and in children. Adaptations in body composition
and Olorgesailie (Kenya) and Swartkrans (South Africa), that distinguish humans from other primates were most
dated between 1.5 and 1.4 mya [40]. At these early times likely required to meet the metabolic needs of brain ex-
fire use was most likely occasional, depending on fire col- pansion. This is consistent with the fact that humans have
lected from natural sources, and may have not signifi- the highest body fat level at birth among mammalian
cantly impacted on food processing. However, exploita- species [50]. In fact, due to the anatomical constrains of
tion of fire for cooking was to become quite systematic the bipedal female pelvis, human newborns have a rela-
later in human evolution. Cooking gelatinizes animal tively small and immature brain, which rapidly develops
connective tissues, allowing easier chewing and diges- postnatally, with major energetic demands [51]. Fat is less
tion, facilitates the digestion of complex carbohydrates in metabolically expensive than muscle, produces agents
vegetables and permits the consumption of plant foods that regulate physiological processes directly related to
inedible or toxic when raw [38, 41]. Thus fire taming, carbohydrate and fat metabolism and provides a supply
which like tool use is a cultural trait, contributed to di- of stored energy usable in response to food deprivation
etary flexibility and quality, and through this, to biologi- [52, 53]. Thus the expansion of the cerebral hemispheres
cal evolution. may have promoted increased body fatness and reduced
muscle mass in the human lineage compared to other pri-
mates.
Metabolic and Dietary Constraints on Brain Size

The striking absolute and relative increase in brain Origin and Spread of H. sapiens, the Perfected
size along the evolutionary sequence that, through the H. Hunter-Gatherer
ergaster/erectus stage, led to our species, H. sapiens, oc-
curred through genetic processes that largely remain to The analysis of mtDNA and Y chromosome variation
be clarified. Primary microcephaly, a rare genetic disor- of modern human populations, supplemented by data on
der due to deficient neurogenesis in which the brain is other nuclear DNA variation and by phylogenetic studies
severely reduced in size but architecturally normal, may of human-specific pathogens, supports the view that our
provide clues to such processes [42]. Evolutionary studies own species, H. sapiens, originated quite suddenly in Af-
of two of the known primary microcephaly-causing rica less than 200,000 years ago (200 kya), from an ad-
genes, microcephalin (MCPH1) and abnormal spindle- vanced ergaster/erectus population [54–57]. This is in
like microcephaly associated (ASPM), which encode pro- good agreement with the fossil evidence [58, 59]. In fact,
teins that influence neurogenic mitosis, reveal clear evi- the earliest isotopically well dated fossils attributed to our
dence for positive selection in the human lineage [43– species, from the Kibish Formation of the Omo River and
46]. from Herto, Middle Awash, both in southern Ethiopia,
Nonetheless, a diet including energy-dense foods that have suggested estimated ages of 200–190 kya and 160–
provided the full complement of nutrients must have 154 kya respectively. These are quite consistent with the
been a prerequisite for the selection of the genetic varia- timeframe independently inferred from the above-men-
tion that allowed encephalization (fig. 4) [47]. The brain tioned genetic studies. H. sapiens spread from Africa to
has much greater energy demands per unit weight than southern Eurasia by approximately 100 kya, and by about
muscle and, unlike muscle, its metabolism cannot be 50–30 kya appears to have replaced, apparently with no
down-regulated to conserve energy [48]. The brain ac- interbreeding, all the continental Eurasian human vari-
counts for about 20–25% of the resting metabolic rate in ants that had evolved from the earlier dispersal of H. erec-
adult humans, compared to about 8–10% in other extant tus, such as the well-known Neanderthals in Europe.
primates and 3–5% in most non-primate mammals. However, the spread of H. sapiens was not limited to Eur-
These figures are much higher in newborns, where over asia, as its mobility and technology very soon allowed
80% of the basal metabolic rate may be due to the brain colonization of Australia, and, later, near the end of the
alone, and in children, where, at about 5 years of age, the last glaciation, of the Americas [60]. Nonetheless, because
brain may account for over 40% of the resting energy de- of our relatively recent origin, the genetic legacy of our
mand [49]. Thus, the striking expansion of the cerebral species is African, and the highest diversity of the human
hemispheres in the Homo lineage necessitated a higher genome is still to be found in Africa, where variation ac-
quality diet, particularly in pregnant or breast-feeding fe- cumulated and was selected over a much longer period of
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time [57]. This is certainly relevant to the genetic varia-
tion that affects nutrition and metabolism, which under-
lines the need to include African populations in studies
of nutrigenomics and nutrigenetics [61].
The advantage that permitted the rapid spread of H.
sapiens, to the detriment of other human forms, appears
to lie in the ability to develop better technology, symbol-
ic conceptualization and more complex social structures,
which must have allowed more efficient hunting and bet-
ter adaptation to environmental, seasonal and geograph-
ic variables [60]. The ability to exploit the large mamma-
lian faunas of the Ice Ages is widely documented at
several archaeological sites, most strikingly in the Fran-
co-Cantabric region of Europe, where symbolic Ice Age
art (fig. 5) developed to its highest level [62].
The optimal foraging theory states that energy from Fig. 5. A dramatic hunting scene painted by a Magdalenian artist
foods should be superior to the energy expended in food about 17,000 years ago. It is located at the bottom of the shaft in
procurement. The food choices of the ancient H. sapiens the heart of the cave sanctuary of Lascaux – the ‘Sistine Chapel’
hunter-gatherers living in cold northern climates during of prehistory – in the Périgord region of France. It shows a wound-
the last glaciation must have been prioritized relative to ed bison (Bison priscus) with a barbed spear in its belly, entrails
hanging out, that attacks and probably kills a naked hunter. The
energy return rates, so that whenever and wherever eco- bird nearby has a symbolic significance that escapes our under-
logically possible, animal food – particularly the fattiest standing. Overall, this scene exemplifies the challenging life of
parts – would have been preferred, and larger game ani- the hunters of the Ice Ages, our direct predecessors, who relied on
mals to smaller [63]. Nonetheless, given its spread and the meat of large wild mammals, more or less as the North Amer-
ican Indians of the Great Plains did in the early 19th century.
adaptability, H. sapiens remained a flexible eater, with a
combination of cultural and genetic traits that allowed
quick dietary shifts in relation to geography, seasons, cli-
matic change and social factors [60].
small body size is also advantageous metabolically, in
terms of better heat dispersal, and appears to be linked
‘Pygmy’ Phenotype to faster growth and earlier sexual maturity, which may
be a key advantage in populations with high mortality
Body size is a complex trait influenced by multiple levels in young adults [66–69]. A ‘pygmy’ phenotype has
gene-environment interactions, in which nutrition plays independently evolved in several African, southeast
a central role. In most animals, given adequate food re- Asian and South American populations, and is also doc-
sources, reproductive performance increases with body umented in extinct H. sapiens populations from Pacific
size, mediated by higher survival of offspring from larg- islands [65, 68]. Furthermore, according to very impor-
er females and increased mating success of larger males tant recent findings, this adaptive phenotype may not be
[64]. This may explain the large body sizes documented exclusively linked to our own species, as skeletal remains
in specimens of H. erectus and ancient H. sapiens. How- of a diminutive small-brained hominin found in Late
ever, there is clear evidence that human populations ge- Pleistocene cave deposits strongly suggest that a ‘pygmy’
netically isolated in areas with a combination of complex human closely related to early H. erectus evolved on the
and still poorly understood environmental factors, most island of Flores, Indonesia, surviving up to very recent
notably hot humid climates in dense continental rainfor- times [69–72]. The genetic basis of the pygmy phenotype
ests or tropical/subtropical islands (fig. 6), can be rap- are still unclear, but the GHBP/GHR/IGF1 system ap-
idly selected for small body size: the so-called ‘pygmy’ pears to play a key role in its determination [73, 74]. Her-
phenotype [65]. This phenotype may be partly explained itable epigenetic modifications could provide a link be-
by restrictions on the availability of food, which limits tween the environment and modifications in gene ex-
growth, and to selection for climbing trees and/or mov- pression control that might contribute to adaptive
ing in areas densely covered by vegetation. However, very phenotypes [75, 76].
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 Color version available online
Fig. 6. Human populations genetically isolated in hot continental rainforests or in tropical/subtropical islands
were evolutionarily selected for small body size, or ‘pygmy’ phenotype. We see here a Lobe Pygmy village in
coastal Cameroon, exemplifying a characteristic type of environment where this particular human adaptation
has been developed. Photo courtesy of Ing. P. De Blasio (2009).

Diet-Mediated Evolutionary Impact of the in the New Guinean highlands, about 9,000–6,000 years
Agricultural Revolution ago, in Subsaharan Africa, possibly 4,000–5,000 years ago,
and in Central, North and South America between 5,000
At the end of the last Ice Age the increase in human and 3,000 years ago [79, 80]. The agricultural revolution
populations that were capable of efficient hunting, coupled significantly affected nutrition and health, as it deter-
with the severe biological stress imposed by the glacial mined rise in population density, marked social stratifica-
maximum and by the marked postglacial climatic chang- tion and, therefore, differential access to foods, sedentary
es, determined the decline or extinction of major prey an- lifestyle and an increased workload. Overall poorer nutri-
imal species in several areas of the world [60, 77, 78]. This tion – reflecting reduced meat intake, reduced mineral ab-
appears to have triggered a global food crisis, which stim- sorption due to cereal-based diets, and seasonal monoph-
ulated migrations and the development of the new food agy – resulted in the spread of carential diseases, which,
sources, made possible by the transition from foraging and after the Neolithic, are readily evident in the osteoarchae-
hunting to farming and animal husbandry. This major ological record (fig. 7) [81–83]. Significantly, a marked de-
ecological and, hence, nutritional change occurred inde- crease in stature of about 15 cm compared to their paleo-
pendently and spread metachronously in several areas of lithic predecessors also becomes evident in many agricul-
the world, starting first at the Paleolithic-Neolithic transi- tural populations, a phenomenon which in several areas of
tion in the area of the ‘fertile crescent’ of the Middle East, the world may have been reversed only by the spread of the
about 11,000 years ago, then, independently, in the Yangt- affluent Western dietary lifestyles of the 20th century.
zi and Yellow River basins of China, about 9,000 years ago, Furthermore, sedentary life and close contact with domes-
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 a b

Fig. 7. After the agricultural revolution, evidence of carential dis- is characterized by pitting and porosity of the cortical smooth
eases becomes common in the osteoarcheological record, as ex- bone of the roof of the orbit. b Teeth of the cranium showing cir-
emplified here by skeletal material from the Iron Age necropolis cumferential rings of enamel hypoplasia, which may reflect diet
of Alfedena, Abruzzo, Italy (3rd century BCE). a Cranium of a or disease-related stresses during the mineralization of the per-
young individual showing cribra orbitalia, a pathological lesion manent dentition. Photo courtesy of Dr. R. D’Anastasio (G.
which has been associated with iron deficiency anemia and which d’Annunzio University, Chieti, Italy).

tic animals favored the spread of infectious or parasitic Present Challenges

diseases and zoonoses, which until the development of
modern medicine (and then mainly only in affluent areas As discussed before, humans evolved and continue to
of the world) severely impacted on the economy, quality of evolve as a result of gene-environment interactions that
life and life expectancy [81–83]. There is evidence that the are strongly modified by culture and mostly mediated
new agricultural lifestyles determined rapid evolutionary through the diet. Today global changes in diet triggered
adaptations in H. sapiens. In fact, about 700 regions of the by the industrial revolution and promoted by the intro-
human genome appear to have been reshaped within the duction of new food technologies, low physical activity
past 5,000–15,000 years [84–87]. The rapidity of these ge- patterns and globalization, with the ensuing rapid spread
netic processes can be explained by strong selective pres- of untested nutritional models, open new avenues and
sure and genetic drift, often mediated by cultural factors. pose new challenges for the evolution of our species [94,
A notable example of the selection of genetic variants that 95]. The ‘thrifty genotype’ and the ‘thrifty phenotype’
allowed more effective utilization of new staple foods is hypotheses, originally advanced in 1962 by J.V. Neel [96],
provided by the ability to tolerate lactose, which, across suggest that genetic variants determining complex gene-
cultures and geographic regions, is inversely related to the environment interactions, which enable individuals to
timing of the transition to agriculture and to the domesti- deposit fat during periods of food abundance, were ad-
cation of dairy animals [88, 89]. Lactase level is controlled vantageous to survival and/or fertility under the condi-
by the enhancer element upstream of the lactase gene, and tions of periodic famine that, up to a recent past, impact-
different lactase-persistence alleles appear to have been in- ed on most agricultural societies. In the modern affluent
dependently selected in diverse populations that heavily societies, such ‘thrifty’ alleles would be highly detrimen-
relied on milk and dairy products in Europe and in Africa tal, being implicated in the pathogenesis of the set of com-
[90, 91]. Another remarkable example of genetic adapta- plex degenerative diseases linked to the metabolic syn-
tion is the ability to better digest starchy foods, which de- drome, namely type 2 diabetes, cardiovascular disease
pends on higher mean salivary amylase gene copy number and cancer [97–99].
selected in agricultural populations with high-starch diets Cultural elaboration and transmission of adaptive di-
[92, 93]. ets and of specific food preparation techniques played a
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major role in allowing adaptations to diverse food envi- treatment makes niacin, biochemically bound in maize,
ronments in most of the world’s pre-industrial societies nutritionally available and thus reduces the severity of
[100]. Unbalanced population growth, global admixture, niacin deficiency, which may cause pellagra in people
loss of cultural roots and strong economic pressures ig- that consume quasi-monophagic maize-based diets [104].
nore genetic and cultural factors that differentiate human This led to the development of the terrible scourge of pel-
populations with respect to dietary adaptations [101]. An lagra, that up to the dawn of the 20th century, haunted
early historical example of the undesirable health conse- the countryside of northern Italy [102].
quences of dietary globalization is provided by the ap- Presently, there is a double threat, related on one side
pearance of pellagra in Mediterranean Europe, particu- to inadequate access to foods, mostly in the developing
larly in northern Italy, following the ‘post-Columbian’ world, and on the other, mostly but not only in the devel-
dietary revolution [102]. During the 16th and 17th centu- oped world, to the epidemic diffusion of complex chron-
ries, porridge (polenta), the central component of the diet ic degenerative diseases, such as atherosclerosis, diabetes
of the poor North Italian peasantry, became almost ex- and cancer. These diseases often reflect imbalances be-
clusively based on flour obtained from maize, a Central tween genetic/metabolic backgrounds and diet. There is
American cereal which was easier to grow and therefore an urgent need to implement intervention policies that
less costly then native Italian cereals. Unfortunately, be- effectively contribute to the global diffusion of food secu-
cause of lack of cultural adaptation, maize porridge was rity and safety. Such actions require a better understand-
prepared without a traditional procedure developed by ing of diet-mediated gene-environment interactions. We
the native peoples of the New World (nixtamalization), should take into account the cultural and genetic legacy
which required treatment of maize with slaked lime or of our evolutionary past to meet the food-related chal-
other alkaline products like plant ashes [103]. This alkali lenges that our species is presently facing.

References

1 Dobzhansky T: Nothing in biology makes 9 Wood B, Lonergan N: The hominin fossil re- 16 McGrewg WC: Culture in non-human pri-
sense except in the light of evolution. Am cord: taxa, grades and clades. J Anat 2008; mates. Annu Rev Anthropol 1998; 27: 301–
Biol Teach 1973; 35:125–129. 212:354–376. 328.
2 Avise CJ, Ayala FJ: In the light of evolution. 10 Maslin MA, Christensen B: Tectonics, orbit- 17 Tocheri MW, Orr CM, Jacofsky MC, Marzke
I. Adaptation and complex design. Proc Natl al forcing, global climate change, and human MW: The evolutionary history of the hom-
Acad Sci USA 2007;104:8563–8566. evolution in Africa: introduction to the Af- inin hand since the last common ancestor of
3 Darwin C: On The Origin of Species by rican paleoclimate special volume. J Hum Pan and Homo. J Anat 2008;212:544–562.
Means of Natural Selection, ed. 1. London, Evol 2007;53:443–464. 18 Milton K: The critical role played by animal
John Murray, 1859. 11 Teaford MF, Ungar PS: Diet and the evolu- source foods in human (Homo) evolution. J
4 Ayala FJ: Darwin’s greatest discovery: design tion of the earliest human ancestors. Proc Nutr 2003;133(suppl 2):3886S–3892S.
without designer. Proc Natl Acad Sci USA Natl Acad Sci USA 2000;97:13506–13511. 19 Foley RA: The evolutionary consequences of
2007;104(suppl 1):8567–8573. 12 Lucas PW, Constantino PJ, Wood BA: Infer- increased carnivory in hominids; in Stan-
5 Abzhanov A, Protas M, Grant BR, Grant PR, ences regarding the diet of extinct hominins: ford CB, Bunn TH (eds): Meat-Eating and
Tabin CJ: Bmp4 and morphological varia- structural and functional trends in dental Human Evolution. New York, Oxford Uni-
tion of beaks in Darwin’s finches. Science and mandibular morphology within the versity Press, 2001, pp 305–331.
2004;305:1462–1465. hominin clade. J Anat 2008; 212:486–500. 20 Bunn TH, Stanford CB: Research trajectories
6 Schneider RA: How to tweak a beak: molecu- 13 Robinson PT: A literature review of dental on hominid meat-eating; in Stanford CB,
lar techniques for studying the evolution of pathology and aging by dental means in non- Bunn TH (eds): Meat-Eating and Human
size and shape in Darwin’s finches and other domestic animals: part II. J Zoo An Med Evolution. New York, Oxford University
birds. Bioessays 2007;29:1–6. 1979;10:81–91. Press, 2001, pp 350–360.
7 Jheon AH, Schneider RA: The cells that fill 14 Clark AG, Glanowski S, Nielsen R, Thomas 21 Tappen M: Deconstructing the Serengeti; in
the bill: neural crest and the evolution of cra- PD, Kejariwal A, Todd MA, Tanenbaum DM, Stanford CB, Bunn TH (eds): Meat-Eating
niofacial development. J Dent Res 2009; 88: Civello D, Lu F, Murphy B, Ferriera S, Wang and Human Evolution. New York, Oxford
12–21. G, Zheng X, White TJ, Sninsky JJ, Adams University Press, 2001, pp 13–33.
8 Herrel A, Huyghe K, Vanhooydonck B, MD, Cargill M: Inferring nonneutral evolu- 22 DeVault TL, Rhodes OE, Shivik JA: Scaveng-
Backeljau T, Breugelmans K, Grbac I, Van tion from human-chimp-mouse ortholo- ing by vertebrates: behavioral, ecological,
Damme R, Irschick DJ: Rapid large-scale gous gene trios. Science 2003; 302: 1960– and evolutionary perspectives on an impor-
evolutionary divergence in morphology and 1963. tant energy transfer pathway in terrestrial
performance associated with exploitation of 15 Somel M, Creely H, Franz H, Mueller U, ecosystems. Oikos 2003;102:225–234.
a different dietary resource. Proc Natl Acad Lachmann M, Khaitovich P, Pääbo S: Hu- 23 Plummer T: Flaked stones and old bones: bi-
Sci USA 2008;105:4792–4795. man and chimpanzee gene expression differ- ological and cultural evolution at the dawn
ences replicated in mice fed different diets. of technology. Am J Phys Anthropol
PLoS ONE 2008;3:e1504. 2004;(suppl 39):118–164.
198.143.58.65 - 11/1/2015 10:46:01 PM
Universita degli Studi di Bologna

100 J Nutrigenet Nutrigenomics 2009;2:91–102 Verginelli /Aru /Battista /

Mariani-Costantini
Downloaded by:
24 Domínguez-Rodrigo M, Pickering TR, 39 Wobber V, Hare B, Wrangham R: Great apes 53 Wolfgang MJ, Lane MD: Control of energy
Semaw S, Rogers MJ: Cutmarked bones from prefer cooked food. J Hum Evol 2008; 55: homeostasis: role of enzymes and intermedi-
Pliocene archaeological sites at Gona, Afar, 340–348. ates of fatty acid metabolism in the central
Ethiopia: implications for the function of the 40 Brain CK, Sillent A: Evidence from the nervous system. Annu Rev Nutr 2006;26:23–
world’s oldest stone tools. J Hum Evol 2005; Swartkrans cave for the earliest use of fire. 44.
48:109–121. Nature 1988;336:464–466. 54 Pakendorf B, Stoneking M: Mitochondrial
25 Mann N: Dietary lean red meat and human 41 Wrangham R, Conklin-Brittain NL: Cook- DNA and human evolution. Annu Rev Ge-
evolution. Eur J Nutr 2000;39:71–79. ing as a biological trait. Comp Biochem nomics Hum Genet 2005;6:165–183.
26 Babin PJ, Gibbons GF: The evolution of plas- Physiol A 2003;136:35–46. 55 Underhill PA, Kivisild T: Use of Y chromo-
ma cholesterol: direct utility or a ‘spandrel’ 42 Woods CG, Bond J, Enard W: Autosomal re- some and mitochondrial DNA population
of hepatic lipid metabolism? Prog Lipid Res cessive primary microcephaly (MCPH): a re- structure in tracing human migrations.
2009;48:73–91. view of clinical, molecular, and evolutionary Annu Rev Genet 2007;41:539–564.
27 Ley RE, Hamady M, Lozupone C, Turn- findings. Am J Hum Genet 2005; 76: 717– 56 Linz B, Balloux F, Moodley Y, Manica A, Liu
baugh PJ, Ramey RR, Bircher JS, Schlegel 728. H, Roumagnac P, Falush D, Stamer C,
ML, Tucker TA, Schrenzel MD, Knight R, 43 Dorus S, Vallender EJ, Evans PD, Anderson Prugnolle F, van der Merwe SW, Yamaoka Y,
Gordon JI: Evolution of mammals and their JR, Gilbert SL, Mahowald M, Wyckoff GJ, Graham DY, Perez-Trallero E, Wadstrom T,
gut microbes. Science 2008;320:1647–1651. Malcom CM, Lahn BT: Accelerated evolu- Suerbaumand S, Achtman M: An African
28 Antón SC, Leonard WR, Robertson ML: An tion of nervous system genes in the origin of origin for the intimate association between
ecomorphological model of the initial homi- Homo sapiens. Cell 2004;119:1027–1040. humans and Helicobacter pylori. Nature
nid dispersal from Africa. J Hum Evol 2002; 44 Mekel-Bobrov N, Posthuma D, Gilbert SL, 2007;445:915–918.
43:773–785. Lind P, Gosso MF, Luciano M, Harris SE, 57 Campbell MC, Tishkoff SA: African genetic
29 Carbonell E, Bermudez de Castro JM, Pares Bates TC, Polderman TJ, Whalley LJ, Fox H, diversity: implications for human demo-
JP, Alfredo Perez-Gonzalez AP, Cuenca-Bes- Starr JM, Evans PD, Montgomery GW, Fer- graphic history, modern human origins, and
cos G, Olle A, Mosquera M, Huguet R, van nandes C, Heutink P, Martin NG, Boomsma complex disease mapping. Annu Rev Ge-
der Made J, Rosas A, Sala R, Vallverdu J, DI, Deary IJ, Wright MJ, de Geus EJ, Lahn nomics Hum Genet 2008;9:403–433.
Garcıa N, Granger DE, Martinon-Torres M, BT: The ongoing adaptive evolution of ASPM 58 McDougall I, Brown FH, Fleagle JG: Strati-
Rodrıguez XP, Stock GM, Verges JP, Allue E, and microcephalin is not explained by in- graphic placement and age of modern hu-
Burjachs F, Caceres I, Canals A, Benito A, creased intelligence. Hum Mol Genet 2007; mans from Kibish, Ethiopia. Nature 2005;
Diez C, Lozano M, Mateos A, Navazo M, Ro- 16:600–608. 433:733–736.
driguez J, Rosell J, Arsuaga JL: The first 45 Ponting C, Jackson AP: Evolution of primary 59 White TD, Asfaw B, DeGusta D, Gilbert,
hominin of Europe. Nature 2008; 452: 465– microcephaly genes and the enlargement of Richards GH, Suwa GD, Howell FC: Pleisto-
470. primate brains. Curr Opin Genet Dev 2005; cene Homo sapiens from Middle Awash,
30 Anton S: Natural history of Homo erectus. 15:241–248. Ethiopia. Nature 2003;423:742–747.
Yearb Phys Anthropol 2003;46:126–170. 46 Currat M, Excoffier L, Maddison W, Otto SP, 60 Holt BM, Formicola V: Hunters of the Ice
31 Mariani-Costantini R, Ottini L, Caramiello Ray N, Whitlock MC, Yeaman S: Comment Age: the biology of Upper Paleolithic people.
S, Palmirotta R, Mallegni F, Rossi A, Frati L, on ‘Ongoing adaptive evolution of ASPM, a Yearb Phys Anthropol 2008;51:70–99.
Capasso L: Taphonomy of the fossil hominid brain size determinant in Homo sapiens’ and 61 Sirugo G, Hennig BJ, Adeyemo AA, Matim-
bones from the Acheulean site of Castel di ‘Microcephalin, a gene regulating brain size, ba A, Newport MJ, Ibrahim ME, Ryckman
Guido near Rome, Italy. J Hum Evol 2001;41: continues to evolve adaptively in humans’. KK, Tacconelli A, Mariani-Costantini R,
211–225. Science 2008;320:1647–1651. Novelli G, Soodyall H, Rotimi CN, Ramesar
32 Fernández-Jalvo Y, Carlos Díez J, Cáceres I, 47 Leonard WR: Food for thought: dietary RS, Tishkoff SA, Williams SM: Genetic stud-
Rosell J: Human cannibalism in the Early change was a driving force in human evolu- ies of African populations: an overview on
Pleistocene of Europe (Gran Dolina, Sierra tion. Sci Am 2002;287:106–115. disease susceptibility and response to vac-
de Atapuerca, Burgos, Spain). J Hum Evol 48 Aiello LC, Wheeler P: The expensive-tissue cines and therapeutics. Hum Genet 2008;
1999;37:591–622. hypothesis: the brain and the digestive sys- 123:557–598.
33 Defleur A, White T, Valensi P, Slimak L, Cré- tem in human and primate evolution. Curr 62 Teyssandier N: Revolution or evolution: the
gut-Bonnoure E: Neanderthal cannibalism Anthropol 1995;36:199–221. emergence of the Upper Paleolithic in Eu-
at Moula-Guercy, Ardeche, France. Science 49 Leonard WR, Snodgrass JJ, Robertson ML: rope. World Archaeology 2008; 40:493–519.
1999;286:128–131. Effects of brain evolution on human nutri- 63 Eaton SB, Konner MJ: Paleolithic nutrition.
34 Marlar RA, Leonard BL, Billman BR, Lam- tion and metabolism. Annu Rev Nutr 2007; N Engl J Med 1985;312:283–289.
bert PM, Marlar JE: Biochemical evidence of 27:311–327. 64 LaBarbera M: Analyzing body size as a factor
cannibalism at a prehistoric Puebloan site in 50 Kuzawa CW: Adipose tissue in human infan- in ecology and evolution. Annu Rev Ecol
southwestern Colorado. Nature 2000; 407: cy and childhood: an evolutionary perspec- System 1989;20:97–117.
74–78. tive. Yrbk Phys Anthropol 1998;41:177–209. 65 Perry GH, Dominy NJ: Evolution of the hu-
35 Diamond JM: Talk of cannibalism. Nature 51 Wittman AB, Wall LL: The evolutionary man pygmy phenotype. Trends Ecol Evol
2000;407:25–26. origins of obstructed labor: bipedalism, 2009;24:218–225.
36 Stoneking M: Widespread prehistoric hu- encephalization, and the human obstetric 66 Roff DA, Heibo E, Vøllestad LA: The impor-
man cannibalism: easier to swallow? Trends dilemma. Obstet Gynecol Surv 2007;62:739– tance of growth and mortality costs in the
Ecol Evol 2003; 18:499–500. 748. evolution of the optimal life history. J Evol
37 Caceres I, Lozano M, Saladie P: Evidence for 52 Dulloo AG, Jacquet J: Adaptive reduction in Biol 2006; 19:1920–1930.
Bronze Age cannibalism in El Mirador Cave basal metabolic rate in response to food de- 67 Migliano AB, Vinicius L, Lahr MM: Life his-
(Sierra de Atapuerca, Burgos, Spain). Am J privation in humans: a role for feedback sig- tory trade-offs explain the evolution of hu-
Phys Anthropol 2007;133:899–917. nals from fat stores. Am J Clin Nutr 1998;68: man pygmies. Proc Natl Acad Sci USA 2007;
38 Wrangham RW, Jones JH, Laden G, Pilbeam 599–606. 104:20216–20219.
D, Conklin-Brittain N: The raw and the sto- 68 Berger LR, Churchill SE, De Klerk B, Quinn
len: cooking and the ecology of human ori- RL: Small-bodied humans from Palau, Mi-
gins. Curr Anthropol 1999; 40:567–594. cronesia. PLoS ONE. 2008;3:e1780.
198.143.58.65 - 11/1/2015 10:46:01 PM
Universita degli Studi di Bologna

Nutrigenetics and Human Evolution J Nutrigenet Nutrigenomics 2009;2:91–102 101

Downloaded by:
69 Brown P, Sutikna T, Morwood MJ, Soejono 82 Diamond J: Evolution, consequences and fu- 93 Perry GH: The evolutionary significance of
RP, Jatmiko, Saptomo EW, Due RA: A new ture of plant and animal domestication. Na- copy number variation in the human ge-
small-bodied hominin from the Late Pleisto- ture 2002;418:700–707. nome. Cytogenet Genome Res 2008; 123:
cene of Flores, Indonesia. Nature 2004; 431: 83 Armelagos GJ, Brown PJ, Turner B: Evolu- 283–287.
1055–1061. tionary, historical and political economic 94 Drewnowski A, Popkin BM: The nutrition
70 Morwood MJ, Brown P, Jatmiko, Sutikna T, perspectives on health and disease. Soc Sci transition: new trends in the global diet.
Saptomo EW, Westaway KE, Due RA, Rob- Med. 2005;61:755–765. Nutr Rev 1997;55:31–43.
erts RG, Maeda T, Wasisto S, Djubiantono T: 84 Voight BF, Kudaravalli S, Wen X, Pritchard 95 The State of Food Insecurity in the World,
Further evidence for small-bodied hominins JK: A map of recent positive selection in the 2006. Rome, Food and Agriculture Organi-
from the Late Pleistocene of Flores, Indone- human genome. PLoS Biol 2006; 4:e72. zation of the United Nations (FAO), 2006.
sia. Nature 2005;437:1012–1017. 85 Balter M: Evolutionary genetics: are humans 96 Neel JV: Diabetes mellitus: a ‘thrifty’ geno-
71 Argue D, Donlon D, Groves C, Wright R: still evolving? Science 2005;309:234–237. type rendered detrimental by ‘progress’?
Homo floresiensis: microcephalic, pygmoid, 86 Patin E, Quintana-Murci L: Demeter’s lega- Am J Hum Genet 1962;14:353–362.
Australopithecus, or Homo? J Hum Evol cy: rapid changes to our genome imposed by 97 Prentice AM: Early influences on human
2006;51:360–374. diet. Trends Ecol Evol 2008; 23:56–59. energy regulation: thrifty genotypes and
72 Gordon AD, Nevell L, Wood B: The Homo 87 Barreiro LB, Laval G, Quach H, Patin E, thrifty phenotypes. Physiol Behav 2005;86:
floresiensis cranium (LB1): size, scaling, and Quintana-Murci L: Natural selection has 640–645.
early Homo affinities. Proc Natl Acad Sci driven population differentiation in modern 98 Stoger R: The thrifty epigenotype: an ac-
USA 2008;105:4650–4655. humans. Nat Genet 2008;40:340–345. quired and heritable predisposition for
73 Baumann G, Shaw MA, Merimee TJ: Low 88 Beja-Pereira A, Luikart G, England PR, obesity and diabetes? BioEssays 2008; 30:
levels of high-affinity growth hormone- Bradley DG, Jann OC, Bertorelle G, Cham- 156–166.
binding protein in African pygmies. N Engl berlain AT, Nunes TP, Metodiev S, Ferrand 99 Prentice AM, Hennig BJ, Fulford AJ: Evolu-
J Med 1989;320:1705–1709. N, Erhardt G: Gene-culture coevolution be- tionary origins of the obesity epidemic:
74 Dávila N, Shea BT, Omoto K, Mercado M, tween cattle milk protein genes and human natural selection of thrifty genes or genetic
Misawa S, Baumann G: Growth hormone lactase genes. Nat Genet 2003;35:311–313. drift following predation release? Int J Obes
binding protein, insulin-like growth factor-I 89 Bersaglieri T, Sabeti PC, Patterson N, Van- (Lond) 2008;32:1607–1610.
and short stature in two pygmy populations derploeg T, Schaffner SF, Drake JA, Rhodes 100 Mariani-Costantini A: Natural and cultur-
from the Philippines. J Pediatr Endocrinol M, Reich DE, Hirschhorn JN: Genetic signa- al influences on the evolution of the human
Metab 2002;15:269–276. tures of strong recent positive selection at the diet: background of the multifactorial pro-
75 Jirtle RL, Skinner MK: Environmental epig- lactase gene. Am J Hum Genet 2004;74:1111– cesses that shaped the eating habits of West-
enomics and disease susceptibility. Nat Rev 1120. ern societies. Nutrition 2000;16:483–486.
Genet 2007;8:253–262. 90 Tishkoff SA, Reed FA, Ranciaro A, Voight 101 Hawkes C: Uneven dietary development:
76 Hunter P: We are what we eat: the link be- BF, Babbitt CC, Silverman JS, Powell K, linking the policies and processes of global-
tween diet, evolution and non-genetic inher- Mortensen HM, Hirbo JB, Osman M, Ibra- ization with the nutrition transition, obe-
itance. EMBO Rep 2008;9:413–415. him M, Omar SA, Lema G, Nyambo TB, sity and diet-related chronic diseases. Glob-
77 Pushkina D, Raia P: Human influence on Ghori J, Bumpstead S, Pritchard JK, Wray al Health 2006;2:4.
distribution and extinctions of the Late GA, Deloukas P: Convergent adaptation of 102 Mariani-Costantini R, Mariani-Costantini
Pleistocene Eurasian megafauna. J Hum Evol human lactase persistence in Africa and Eu- A: An outline of the history of pellagra in
2008;54:769–782. rope. Nat Genet 2007;39:31–40. Italy. J Anthropol Sci 2007; 85: 163–171.
78 Barnosky AD, Koch PL, Feranec RS, Wing 91 Enattah NS, Jensen TG, Nielsen M, Lewinski 103 Brenton BP: Piki, polenta and pellagra:
SL, Shabel AB: Assessing the causes of late R, Kuokkanen M, Rasinpera H, El-Shanti H, maize, nutrition and nurturing the natural,
Pleistocene extinctions on the continents. Seo JK, Alifrangis M, Khalil IF, Natah A, Ali in Hosking R (ed): Nurture. Proceedings of
Science 2004;306:70–75. A, Natah S, Comas D, Mehdi SQ, Groop L, the Oxford Symposium on Food and Cook-
79 Weiss E, Wetterstrom W, Nadel D, Bar-Yosef Vestergaard EM, Imtiaz F, Rashed MS, Mey- ery 2003. Bristol, Footwork, 2004, pp 36–
O: The broad spectrum revisited: Evidence er B, Troelsen J, Peltonen L: Independent in- 50.
from plant remains. Proc Natl Acad Sci USA troduction of two lactase-persistence alleles 104 Kodicek E, Braude R, Kan SK, Mitchell KG:
2004;101:9551–9555. into human populations reflects different The effect of alkaline hydrolysis of maize
80 Diamond J, Bellwood P: Farmers and their history of adaptation to milk culture. Am J on the availability of its nicotinic acid to the
languages: the first expansions. Science Hum Genet 2008;82: 57–72. pig. Brit J Nutr 1956;10:51–67.
2003;300:597–602. 92 Perry GH, Dominy NJ, Claw KG, Lee AS,
81 Diamond J: Guns, Germs, and Steel: the Fiegler H, Redon R, Werner J, Villanea FA,
Fates of Human Societies. New York, Nor- Mountain JL, Misra R, Carter NP, Lee C,
ton, 1999. Stone AC: Diet and the evolution of human
amylase gene copy number variation. Nat
Genet 2007;39:1256–1260.
198.143.58.65 - 11/1/2015 10:46:01 PM
Universita degli Studi di Bologna

102 J Nutrigenet Nutrigenomics 2009;2:91–102 Verginelli /Aru /Battista /

Mariani-Costantini
Downloaded by: