REVIEWS
PHYSIOLOGY 31: 392–397, 2016. Published October 5, 2016; doi:10.1152/physiol.00013.2016
Evolutionary Medicine: The Ongoing
Evolution of Human Physiology and
Metabolism
The field of evolutionary medicine uses evolutionary principles to understand
Frank Rühli,1 Katherine van Schaik,1,2
and Maciej Henneberg1,3
1
Institute of Evolutionary Medicine, University of Zurich, Zurich,
Switzerland; 2Harvard Medical School and Harvard Department
of the Classics, Harvard University, Cambridge, Massachusetts;
and 3Adelaide Medical School, The University of Adelaide,
Adelaide, Australia
frank.ruehli@iem.uzh.ch
changes in human anatomy and physiology that have occurred over time in
response to environmental changes. Through this evolutionary-based approach, we can understand disease as a consequence of anatomical and
physiological “trade-offs” that develop to facilitate survival and reproduction.
We demonstrate how diachronic study of human anatomy and physiology is
fundamental for an increased understanding of human health and disease.
Adaptations of the Human Body
Humans are animals, and, like the animals we
study, we possess bodies that change in response
to the features of our external and internal environments. We have done much to affect our interactions with these environments: we have
insulated our bodies from climate, produced and
chemically processed our food (for example,
through fermentation or additives), removed much
of the disease causes we might encounter (for example, parasites and bacteria), and, with the help
of technology, have learned to repair our bodies
(prosthetics) to increase our physiological performance both physically (eyeglasses and hearing
aids) and mentally (medications to enhance concentration). Although it may sometimes be difficult
to identify precisely the nature of the relationship
between our environments and our bodies, and to
demonstrate why and how the human body
changes, we can at least observe how it has
changed over the last few millennia.
A classic example of the relationship between
health and the evolution of the human body involves osteoarthritis and the development of erect
bipedal locomotion. Progressive degenerative arthritic changes in the spine and lower limb are a
biomechanical consequence of upright posture
and locomotion (2, 20, 23). Another relatively more
recent example of human evolution, the appearance of multiple renal arteries and veins, involves
modern populations rather than past populations.
It suggests that there are now, more so than in the
past, alterations of embryonic development that
affect the ascent of the kidneys from their initial
position (31). Changes in macroscopic traits over
time can be studied through examination of skeletal human remains, mummies, the fossil record,
and patient’s records and images. Furthermore,
such changes at the macroscopic or morphological
392
level could reasonably be assumed to mirror
changes at the microscopic or metabolic level. For
example, micro-evolutionary trends of human hormones and their impact on human morphology
have already been proposed (27, 28).
Evolution of various biological characteristics
proceeds at various rates in various populations in
different periods. The direction and speed of such
evolution depend on disturbances in homeostasis.
Although mutations occur at fairly stable rates,
natural selection, especially in its purging form, is
becoming relaxed as a result of decreasing mortality and controlled fertility (30). The relationship
between evolution and human physiology-and the
evidence that evolution continues to affect human
physiology—means that research in physiology
should engage with evolutionary perspectives and
hypotheses. This paper highlights important evolutionary alterations of human physiology, both in
the past and in the present, a topic that is a core
part of the interdisciplinary research field of evolutionary medicine (also called Darwinian medicine). Study of the formation of human physiology
in the past yields a clearer understanding of the
etiology of many current challenges to human
health and wellness (FIGURE 1). Furthermore,
study of the evolution of disease could facilitate
improved methods to address these challenges,
from the research bench, to the patient’s bedside,
to the offices of lawmakers seeking improved public health strategies.
Evolutionary Medicine and
Selected Physiological Processes
Evolutionary medicine has been defined as a research field applying evolutionary principles to understand human health and disease, and the
mechanisms that change health and disease over
time (32). Its theoretical concepts are primarily
based on established and well known principles
1548-9213/16 ©2016 Int. Union Physiol. Sci./Am. Physiol. Soc.
Downloaded from journals.physiology.org/journal/physiologyonline (054.163.042.124) on May 27, 2020.
REVIEWS
and terminology used in evolutionary biology and
genetics. These include major forces of evolution:
mutations, natural and sexual selection, inbreeding, assortative mating, gene flow, and genetic
drift. Also relevant for evolutionary medicine are
the effects of epigenetic and physiological adaptability to general and local environmental factors.
Human anatomy and physiology are regarded as
evolutionary trade-offs, consequences of adaptation of the human body to its living circumstances.
The goal of evolutionary medicine studies is to use
this evolutionary biology-based framework to decipher both proximal and ultimate causes of alterations in human health and disease.
There are many examples of studies that address
the relationship between evolution and physiological processes, including research about functional
alleles. For example, the persistence of lactase in
adults is a result of the relatively recent dependence of some human populations on unprocessed milk (34). Other studies have suggested that
the number of amylase gene copies increased as a
result of agricultural production supplying abundant complex carbohydrates (24). The relationship
between hemoglobinopathies and exposure to malaria is well known (26). Additional examples that
illustrate the relationship between evolution and
physiological processes are human adaptations in
oxygen saturation as a consequence of living at
high altitude (40), and even adolescent growth
spurts, since not all societies through human history seem to have experienced this phenomenon
(1, 36).
Hormones provide a particularly nuanced and
complex example of the intersection between
physiology, evolution, and human history. Consider sex hormones in women: Modern females
at healthy body weights (i.e., not over- or under-
weight) who live in developed nations reach their
first ovulatory period at an average age ⬃12.5 yr
(7) and reach menopause at the average age (for
this same demographic) of 51 yr (14). Evidence
suggest that changes in diet, the introduction of
birth control methods, and reductions in the average number of children born per woman have
led to changes in estrogen levels. These changes
in estrogen levels could in turn lead to alterations in metabolism (16). Furthermore, it is increasingly becoming clear that neuro-hormonal
axes, in particular those systems regulated by
dopamine and thyroid hormones, are more responsible for the evolution of human mental abilities than changes in brain anatomy (25). Such
changes in brain physiology could have enabled
better cognition and thus improved behavioral adaptations and potentially an increased proclivity
toward reward- and pleasure-seeking behavior.
Biological Rhythms and
Their Adaptation
Biological rhythms exist in many mammals, including humans, and may be understood as evolutionary adaptations to regularly changing environmental conditions. Prominent among those are
diurnal rhythms of rest and activity. Humans are
diurnal, so their bodies must be prompted to activity during daylight and to rest at night. Diurnal
rhythm is neuro-hormonally regulated, with the
melatonin secreted by the pineal gland playing a
primary role. Since humans need to sleep several
hours out of every 24 hr, maintenance of the diurnal rhythm is crucial for health and normal functioning. Secretion of melatonin is cyclical and can
be altered by changing light exposure and activity
patterns (9).
Substance abuse
FIGURE 1. Pictorial summary of the evolutionary etiology of selected pathologies
PHYSIOLOGY • Volume 31 • November 2016 • www.physiologyonline.org
Downloaded from journals.physiology.org/journal/physiologyonline (054.163.042.124) on May 27, 2020.
393
REVIEWS
Humans’ desire to light their world artificially,
without the light of the sun, has existed for a long
time. The recent discoveries of Homo naledi deep
in the cave system in South Africa may indicate
that humans were already using artificial light over
2 million years ago (3), and the oldest use of fire
has been suggested to have occurred at least 1.5
million years ago (6). In the 19th century, humans
became more adept at creating artificial light when
they invented light sources (kerosene, gas, electricity) that could imitate more effectively the brilliance of daylight. Bright television, computer, and
smartphone screens mean that, today, our eyes are
exposed to more bright lights, more often, than has
previously been the case in human history. This is
contributing to disturbances in sleep and wakefulness (17). Whether and how this change might
contribute to long-term neuro-hormonal changes,
both on the individual and on the species level,
remain to be seen. Recent research has indicated
that women involved in night-shift work are at
greater risk for cardiovascular disease (35), suggesting that alterations to circadian rhythm could
have the potential to contribute to some kind of
evolutionary change.
Cycles on a broader scale–that is, annual cycles–
are less conspicuous in humans than in other animals but are nonetheless present. Manifestations
of annual rhythms include different rates of fertility
and mortality, depending on the season, and correlations between body size and month (or season)
of birth (21, 38). These differences may represent
evolutionary adaptations themselves, or they may
be the consequence of different access to resources
during particular times of the year. At the very
least, such data indicate the ongoing relationship
between human physiology and the external
environment.
Aging Vasculature: An Evolutionary
Perspective
Global vascular disease burden (including cardiovascular, peripheral vascular, and neurovascular
diseases) is great and growing, and it is a major
cause of death worldwide in both developed and
developing nations (22). Much research has focused on identifying causes of vascular damage
and ways to prevent or to reverse pathological degeneration of and damage to vessels (22). As is the
case in other chronic degenerative conditions (e.g.,
osteoporosis, neuro-degeneration), vessels “age”
through lack of maintenance (33). In the second
half of the 20th century, much scientific research
linked problems with vascular maintenance and
with plaque accretion to diet and lifestyle. In the
21st century, however, new research began to suggest other ways of considering etiologies of
394
vascular disease. These studies found that diet was
less important than other issues, such as the integrity of the human immune system and the role of
inflammation in chronic disease (22). Paleopathological data–specifically, study of the occurrence of
cardiovascular disease in mummies from four different pre-modern time periods and locations–
suggested that the modern sedentary lifestyle and
lipid-rich diet may not be as responsible for cardiovascular disease as previously thought. Evidence of prominent plaques was found, for
example, in the abdominal vessels of an Unangan
(Aleutian Islands) woman who lived in the 19th
century CE and died in her late 40s; in an Egyptian
woman in her late 40s who died in an unknown era
during the Pharaonic period; in an Ancestral
Puebloan woman in her late 40s who died between
1500 BCE and 500 CE; and in a woman from ancient Peru, 200 –900 CE, who died in her early 40s.
Similar evidence of vascular disease was found in
the remains of male mummies as well, and at other
places in the vasculature, such as the carotid arteries (33). Such paleopathological findings suggest
the limitations in our understanding of the etiologies of what might be considered a “normal” part
of human aging.
Integument and Interaction With
the Surrounding Environment
Human integument, consisting of epidermis, dermis, and subcutaneous adipose tissue, is the largest single organ of the body. Besides providing
mechanical and biological protection, it plays an
active role in thermoregulation by affording insulation and enabling heat dissipation. Unlike the
integument of our closest primate relatives, human
skin possesses relatively small hairs that are incapable of providing thermal insulation. Instead, it
has been suggested that human body hair evolved
not to provide insulation but to enhance detection of
ectoparasites (11). Other changes in the human body
over time have worked to protect against heat loss,
including differences in humans’ surface area-tobody volume ratio that varies with latitude (4).
Loss of effective hair cover by humans also resulted in the development of the layer of melanin
in the basal stratum of the epidermis. This layer
protects deeper layers of skin against ultraviolet
radiation (5). Amounts of melanin differ widely
among individuals and among populations, with
most of this variation emerging as a consequence
of long-term evolutionary adaptations to different
levels of UV radiation in different areas of the
world (8). A degree of physiological adaptability is
demonstrated by the phenomenon of skin tanning:
melanogenesis in the skin is increased in response
to exposure to UVB light. Together, genetic
PHYSIOLOGY • Volume 31 • November 2016 • www.physiologyonline.org
Downloaded from journals.physiology.org/journal/physiologyonline (054.163.042.124) on May 27, 2020.
REVIEWS
adaptation to the area of origin and the process of
tanning produce protection against the UV radiation that may destroy the living cells of the dermis.
Similarly, melanin accumulation in the iris protects eyes against destructive UV radiation, and
lighter-colored irises tend to be more frequent
among populations in latitudes that receive less
intense UV radiation (18). Migration of individuals
with lighter skin to areas of more intense sun exposure can lead to increased incidence of skin
cancer; migration of individuals with darker skin to
higher latitudes can contribute to the development
of vitamin D deficiency (10).
Evolutionary Perspectives
of Homeostasis
The human body is a complex system resulting
from genetic, epigenetic, and external factors, and
in normal conditions there is an energy homeostasis. However, alterations of our gene pool (i.e.,
relaxed natural selection leading to accumulation
of regularly appearing random mutations), influences on epigenetic level (e.g., extent of DNAmethylation), or environmental factors (diet,
lifestyle) can lead to disturbances of homeostasis.
Stress in any form– eustress or distress– can lead to
physiological adaptation and thus can result in a
selective advantage or disadvantage of certain
traits. For instance, the flight or fight response,
understood and correctly described even in ancient times (12), is in modern society rarely necessary in its original sense. A biochemical and
physiological basis for its development and evolution can now be indirectly assessed by measuring
cortisol levels in hairs of mummies (37). This type
of analysis can lead us to estimate general physiological stress levels, further enhancing our knowledge of the kind of physiological stress that could
be related to the heightened levels of inflammation
described in the previous section discussing causes
of vascular disease.
Physiological adaptations to a way of life characterized by hunting and gathering, instead of the
relatively stable food supplies that the development of agriculture facilitated, explain human metabolism and our physiological tendency to store
excess calories as energy-rich fat to combat potential times of scarce resources. This also at least
partially explains the human preference for fatty,
energy-rich food. Today, when food is readily available and minimal effort is required to obtain it, the
physiological system that encouraged survival in
times of famine is now contributing to obesity and
its associated pathologies (13, 16).
Consider also the biomolecular aspect of human
metabolism. Hunter-gathering humans were accustomed to eat large amounts of protein (for ex-
ample, when a large animal was killed) with some
degree of regularity, although probably with fairly
long gaps of time in between kills. With this diet
characterized by large loads of protein, interspersed with plant foodstuffs, the human metabolic system became effective at acquiring energy
from digested amino acids that had to be deaminated before being broken down into pyruvates
used in the citric acid cycle. Any surpluses of the
products of deamination were effectively stored in
adipose tissue by subjecting amino acid-derived
pyruvates to de novo lipogenesis (13, 16). When the
human diet began to include larger quantities of
carbohydrates and fats with the advent of agriculture and pastoralism, easily digestible and easily
absorbed compounds were preferentially used to
fuel the citric acid cycle. Meat requires more time
for digestion: with sufficient energy gains from carbohydrates and fats, the products of protein digestion were stored as fat in adipose tissue, besides
providing essential amino acids for specific processes. This situation persists today, with meat
added to otherwise energetically sufficient meals,
fueling the obesity epidemic (13, 16).
Understanding of the evolutionary aspects of
eating behaviors and metabolism can contribute to
efforts to reduce the prevalence of obesity and
related pathological conditions. It is important to
emphasize, as this evolutionary perspective reminds us, that obesity is not “pathological,” in the
sense that it is a normal outcome of a metabolic
process that evolved to guarantee energy stores.
Certainly, there are many pathological sequelae of
FIGURE 2. Correlation of the prevalence of the Type 1 and Type 2 diabetes mellitus with the opportunity for natural selection in 118 countries based on the data provided by the International Diabetes
Federation and the WHO
Logarithmic scales. Opportunity for natural selection in a given country is measured as the ratio (1 ⫺ Ibs)/Ibs, where Ibs is the Biological State Index. The Biological State Index of a given population expresses a probability of an individual
passing her/his genes to the next generation under the conditions of mortality and
fertility prevailing in this population. The lower the ratio, the less opportunity for
selection exists. For calculations for the Biological State Index and the application
of WHO and International Diabetes Federation, see Refs. 19, 30, and 39.
PHYSIOLOGY • Volume 31 • November 2016 • www.physiologyonline.org
Downloaded from journals.physiology.org/journal/physiologyonline (054.163.042.124) on May 27, 2020.
395
REVIEWS
obesity, including joint damage and insulin resistance, and the evolutionary aspects of insulin have
recently been addressed. A study of 118 countries,
for which data about diabetes mellitus type 1
(DM-1) were available from the International Diabetes Federation (19), suggested a statistically significant relationship between the prevalence of
DM-1 and the relaxation of selection, when controlling for other variables such as income and
urbanization (39) (FIGURE 2). However, the physiological origin of obesity is in the human body’s
carefully evolved systems of energy storage and
homeostasis, and understanding this origin should
augment research about prevention and treatment
of obesity-related conditions like DM-1.
Medical treatment seeks to address both symptoms and causes of pathological conditions, with
causes being the preferred target of treatment
when feasible. Evolutionary medicine explicitly addresses the causes of human physiology–and human pathophysiology–from their origins. Obesity
is an example of a condition with pathological
outcomes that resulted from normal physiological
processes. Considered as a consequence of this
normal metabolic process, “obesity” is a more
complex physiological condition than the term
“disease” implies.
396
We thank Francesco Galassi and Corina Steiner (Institute
of Evolutionary Medicine, University of Zurich) for technical assistance.
Funding for this research was provided by
Mäxi-Foundation.
No conflicts of interest, financial or otherwise, are declared by the author(s).
Author contributions: F.R., K.v.S., and M.H. conception
and design of research; F.R., K.v.S., and M.H. analyzed
data; F.R. and M.H. interpreted results of experiments;
F.R. and M.H. prepared figures; F.R., K.v.S., and M.H.
drafted manuscript; F.R., K.v.S., and M.H. edited and revised manuscript; F.R., K.v.S., and M.H. approved final
version of manuscript; M.H. performed experiments.
References
1.
Artaria M, Henneberg M. The existence of a peak in adolescent’s height increments. Folia Med Indonesiana 44: 196 –
202, 2008.
2.
Battié MC, Videman T, Kaprio J, Gibbons LE, Gill K, Manninen H, Saarela J, Peltonen L. The twin spine study: contributions to a changing view of disc degeneration. Spine J 9:
47–59, 2009.
3.
Berger LR, Hawks J, de Ruiter DJ, Churchill SE, Schmid P,
Delezene LK, Kivell TL, Garvin HM, Williams SA, DeSilva JM,
Skinner MM, Musiba CM, Cameron N, Holliday TW, Harcourt-Smith W, Ackermann RR, Bastir M, Bogin B, Bolter D,
Brophy J, Cofran ZD, Congdon KA, Deane AS, Dembo M,
Drapeau M, Elliott MC, Feuerriegel EM, Garcia-Martinez D,
Green DJ, Gurtov A, Irish JD, Kruger A, Laird MF, Marchi D,
Meyer MR, Nalla S, Negash EW, Orr CM, Radovcic D, Schroeder L, Scott JE, Throckmorton Z, Tocheri MW, VanSickle C,
Walker CS, Wei P, Zipfel B. Homo naledi, a new species of the
genus Homo from the Dinaledi Chamber, South Africa. eLife
2015: 4, 2015.
Outlook
4.
Bogin B, Valera-Silva MI. Leg length, body proportion, and
health: a review with a note on beauty. Int J Environ Res
Public Health 7: 1047–1075, 2010.
As can be observed from the preceding discussion,
evolution influences all aspects of human physiology and pathophysiology and can inform the developments of treatments that are rooted in
mechanistic understandings of disease etiology
(FIGURE 1). It is vitally important that medical
curricula emphasize the evolutionary context of
human physiology (29). In the future, we can anticipate improvements in molecular techniques
that will better enable researchers in the field of
evolutionary medicine to decipher ancient DNA
and RNA, and such next-generation sequencing
techniques will permit more thorough exploration
of the genetic basis for ongoing evolution of physiological processes. Addressing the evolutionary
aspects of modern human physiology helps to explain issues such as disease vulnerability, disease
course, treatment efficacy, and even the definition
of disease itself (vs. the exuberant expression of a
normal physiological process, for example). We
need to understand the evolution and adaptation
of physiological processes in order to understand
more completely how humans can healthily cope
with ongoing changes in our environment. In
short, physiology without an evolutionary perspective is like engineering without physics! 䡲
5.
Brace CL, Henneberg M, Relethford JH. Skin color as an
index of timing in human evolution. Am J Phys Anthropol
Suppl 28: 95–96, 1999.
6.
Brain CK, Sillent A. Evidence from the Swartkrans cave for
the earliest use of fire. Nature 336: 464 – 466, 1998.
7.
Bralić I, Tahirović H, Matanić D, Vrdoljak O, Stojanović-Spehar S, Kovacić V, Blazeković-Milaković S. Association of early
menarche age and overweight/obesity. J Pediatr Endocrinol
Metab 25: 57– 62, 2012.
8.
Brenner M, Hearing VJ. The protective role of melanin
against UV damage in human skin. Photochem Photobiol 84:
539 –549, 2008.
9.
Cajochen C, Kräuchi K, Wirz-Justice AJ. Role of melatonin in
the regulation of human circadian rhythms and sleep. Neuroendocrinol 15: 432– 437, 2003.
10. Chaplin G, Jablonski NG. The human environment and the
vitamin D compromise: Scotland as a case study in human
biocultural adaptation and disease susceptibility. Hum Biol
85: 529 –552, 2013.
11. Dean I, Siva-Jothy MT. Human fine body hair enhances ectoparasite detection. Biol Lett 8: 358 –361, 2012.
12. Galassi FM, Böni T, Rühli FJ, Habicht M. Fight-or-flight response in the ancient Egyptian novel “Sinuhe” (c. 1800 BCE).
Auton Neurosci 195: 27–28, 2016.
13. Genné-Bacon EA. Thinking evolutionarily about obesity. Yale
J Biol Med 87: 99 –112, 2014.
14. Gold EB. The timing of the age at which natural menopause
occurs. Obstet Gynecol Clin North Am 38: 425– 440, 2011.
15. Grantham JP, Henneberg M. The estrogen hypothesis of
obesity. PLos One 9: e99776, 2014.
16. Grantham JP, Staub K, Rühli FJ, Henneberg M. Modern diet
and metabolic variance: a recipe for disaster? Nutr J 13: 15,
2014.
PHYSIOLOGY • Volume 31 • November 2016 • www.physiologyonline.org
Downloaded from journals.physiology.org/journal/physiologyonline (054.163.042.124) on May 27, 2020.
REVIEWS
17. Holzman DC. What’s in a color? The unique human health effects of blue light. Environ Health
Perspect 118: A22–A27, 2010.
18. Hu DN. Photobiology of ocular melanocytes and
melanoma. Photochem Photobiol 81: 506 –509,
2005.
19. International Diabetes Federation. IDF Diabetes
Atlas (1st ed.). Brussels, Belgium: International
Diabetes Federation, 2000.
27. Rühli FJ, Böni T, Henneberg M. Hyperostosis
frontalis interna: archaeological evidence of possible microevolution of human sex steroids?
Homo J Hum Comp Biol 55: 91–99, 2004.
28. Rühli FJ, Henneberg M. Are hyperostosis frontalis interna and leptin linked? A hypothetical approach about hormonal influence on human
microevolution. Med Hypotheses 58: 378 –381,
2002.
35. Vetter C, Devore EE, Wegrzyn LR, Massa J, Speizer FE, Kawachi I, Rosner B, Stampfer MJ,
Schernhammer ES. Association between rotating
night shift work and risk of coronary heart disease among women. JAMA 315: 1726 –1734,
2016.
36. Walker R, Gurven M, Hill K, Migliano A, Chagnon
N, De Souza R, Djurovic G, Hames R, Hurtado
AM, Kaplan H, Kramer K, Oliver WJ, Valeggia C,
Yamauchi T. Growth rates and life histories in
twenty-two small-scale societies. Am J Hum Biol
18: 295–311, 2006.
20. Jurmain RD, Kilgore L. Skeletal evidence of osteoarthritis: a paleopathological perspective.
Ann Rheum Dis 54: 443– 450, 1995.
29. Rühli FJ, Haeusler M, Saniotis A, Henneberg M.
Novel modules to teach evolutionary medicine:
an Australian and a Swiss experience. Med Sci
Educator 26: 375–381, 2016.
21. Krenz-Niedbała M, Puch EA, Kościński K. Season
of birth and subsequent body size: the potential
role of prenatal vitamin D. Am J Hum Biol 23:
190 –200, 2011.
30. Saniotis A, Henneberg M. Medicine could be
constructing human bodies in the future. Med
Hypotheses 77: 560 –564, 2011.
37. Webb E, Thomsonb S, Nelsona A, Whitea C,
Koren G, Rieder M, Van Uum S. Assessing individual systemic stress through cortisol analysis of
archaeological hair. J Archaeol Sci 37: 807– 812,
2010.
31. Satyapal KS, Henneberg M. A possible secular
trend in the incidence of anatomical variation in
the renal vasculature. J Anat 185: 692– 693, 1994.
38. Weber GW, Prossinger H, Seidler H. Height depends on month of birth. Nature 391: 754 –755,
1998.
32. Stearns SC, Medzhitov R. Evolutionary Medicine.
Sunderland, MA: Sinauer Associates, 2016.
39. You WP, Henneberg M. Type 1 diabetes prevalence increasing globally and regionally: the role
of natural selection and life expectancy at birth.
BMJ Open Diabetes Res Care 4: e000161, 2016.
22. Mackay J, Mensah G. The Atlas of Heart Disease
and Stroke. Geneva, Switzerland: World Health
Organization and Centers for Disease Control
and Prevention, 2014.
23. Olshansky SJ, Carnes BA, Butler RN. If humans
were built to last. Sci Am 284: 50 –55, 2001.
24. Perry GH, Dominy NJ, Claw KG, Lee AS, Fiegler
H, Redon R, Werner J, Villanea FA, Mountain JL,
Misra R, Carter NP, Lee C, Stone AC. Diet and
the evolution of human amylase gene copy number variation. Nat Genet 39: 1256 –1260, 2007.
25. Previc FH. Dopamine and the origins of human
intelligence. Brain Cogn 41: 299 –350, 1999.
26. Roberts DJ, Williams TN. Haemoglobinopathies
and resistance to malaria. Redox Rep 8: 304 –310,
2003.
33. Thompson RC, Allam AH, Lombardi GP, Wann
LS, Sutherland ML, Sutherland JD, Soliman MA,
Frohlich B, Mininberg DT, Monge JM, Vallodolid
CM, Cox SL, Abd el-Maksoud G, Badr I, Miyamoto MI, el-Halim Nur el-Din A, Narula J, Finch
CE, Thomas GS. Atherosclerosis across 4000
years of human history: the Horus study of four
ancient populations. Lancet 381: 1211–1222,
2013.
40. Young AJ, Reeves JT. Human adaptation to high
terrestrial altitude. In: Medical Aspects of Harsh
Environments. Volume 2. Falls Church, VA: Bureau of Medicine and Surgery, U.S. Navy, 2002,
p. 644 – 688.
34. Tishkoff SA, Reed FA, Ranciaro A, Voight BF,
Babbitt CC, Silverman JS, Powell K, Mortensen
HM, Hirbo JB, Osman M, Ibrahim M, Omar SA,
Lema G, Nyambo TB, Ghori J, Bumpstead S,
Pritchard JK, Wray GA, Deloukas P. Convergent
adaptation of human lactase persistence in Africa
and Europe. Nat Genet 39: 31– 40, 2007.
PHYSIOLOGY • Volume 31 • November 2016 • www.physiologyonline.org
Downloaded from journals.physiology.org/journal/physiologyonline (054.163.042.124) on May 27, 2020.
397