The Pygmy Short Stature Enigma Cristina Meazza, PhD, Sara Pagani, PhD, Mauro Bozzola, MD Paediatrics Department, University of Pavia, Foundation IRCCS Policlinico San Matteo, Pavia, Italy. Corresponding author: Prof. Mauro Bozzola, MD, Paediatrics Department, University of Pavia, Foundation IRCCS Policlinico San Matteo, Piazzale Golgi 2, 27100 Pavia Tel: +39-0382-502891, Fax: +39-0382-527976, E-mail:
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Evolution of Human Pygmy Phenotype
Abstract
T
he Pygmy populations of Central Africa are known as the shortest human populations worldwide showing an endocrine profile similar to Caucasian individuals with idiopathic short stature. Therefore, the study of these subjects may significantly improve our knowledge of the mechanisms regulating normal growth in humans. In this review we summarize the existing knowledge on Pygmies’ short stature, including evolutionary hypothesis, studies on their GH/IGF-I axis and their immune system functioning. We illustrate in depth our recent studies on the ethnic group of Pygmies called Babinga, living in the forest of Cameroon, suggesting that the size of Pygmy subjects is reduced from birth, compared to a neighbouring population, and that it is associated with reduced GH and GH receptor gene expression. These results provide a research target for future epigenetic investigations and suggest that the short stature of African Pygmies is probably determined by complex genetic systems. Ref: Ped. Endocrinol. Rev. 2011;8(4):394-399 Keywords: African Pygmies, short stature, growth hormone, growth hormone receptor
Various evolutionary hypotheses have been proposed to explain the small body size of Pygmies (Table 1). The adaptive hypothesis stresses the advantages of small size for living in the dense forest with warm and humid conditions, and food limitations. Traditionally, the small body size of human Pygmies has been interpreted as an adaptation in itself for living in dense tropical forests. The advantage of small body size in the forested areas facilitates movement through dense vegetation and climbing in trees in search of food (1). However, the advantage of small size fails to account for the short stature of Pygmy people who live in an open habitat. Cavalli-Sforza suggested that small body size is favoured by the hot, humid climate of the tropical forest. In an environment in which there is a large risk of exhaustion due to the body’s own heat production during exercise, this risk would be minimized by small body size (low mass/area ratio) and the relatively small muscle mass of African Pygmies (1). In striking contrast to this hypothesis, human body size is reduced also in some populations of New Guinea, who live in cold, high mountainous areas (2). Furthermore, the small negritos of the Philippines also live in the mountains, not in the humid lowlands. Small body size might have conferred a selective advantage to Pygmies in habitats like food-limited rainforests by reducing the total caloric intake (3). However, long-standing poor nutrition does not necessarily lead to Pygmy size as shown by other groups who experience frequent food shortages and yet are among the tallest populations in the world (4). Recently, results by Migliano et al. (5) challenged the traditional explanations of Pygmy body size. The authors, by constructing growth curves for Pygmies and neighbouring populations of normal stature, showed that Pygmies terminate their growth at an earlier age than controls. Thus, the smaller adult size is primarily caused by a difference in duration rather than rate of growth. Furthermore, the authors observed that Pygmies have an extremely high mortality rate and an early fertility peak, when compared with non-Pygmy groups. Therefore, the authors suggest that human Pygmy populations
Introduction Small human body size or the “pygmy” phenotype is characteristic of certain African, Southeast Asian and South American populations. African Pygmies, the shortest population on earth, are at the extreme end of the distribution for normal human stature. Therefore, documentation of their growth and hormonal regulation are very important for better understanding the role of genetic and environmental factors in determining human stature. Until now, none of the theories proposed has really explained which hormonal and evolutionary mechanisms are responsible for the short stature of Pygmies. In this review, we summarize the theories reported in the literature that attempt to explain Pygmy short stature.
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Pygmies and Short Stature Hypothesis
In favour
Against
Adaptation to living in dense tropical forest
Small body size is advantageous for getting through the dense vegetation in search of food (1)
Body size is reduced also in Pygmies living in an open habitat (3)
Thermoregulation
Small body size generates less internal heat during activity with fitness advantage in hot and humid climate (1)
People with short stature also live in cold mountainous areas, i.e. Negritos of the Philippines or Semang of Malaysia (2)
Endurance against starvation
Short people are better able to endure starvation since they have reduced energy needs and total caloric intake (3)
African Pygmy hunter-gatherers have a surplus of adequate resources (1)
Life-history factors
Small-bodied populations have an early cessation of growth to facilitate a relatively early age for first reproduction under circumstances of high adult mortality rate (5)
Small-bodied people such as Hadza and !Kung San do not exhibit an high mortality rate (7)
Table 1. Evolutionary explanations of Pygmy phenotype.
and adaptations evolved independently as the result of a history of trade-offs between the fertility benefits of larger body size against the cost of late growth cessation, under circumstances of significant mortality. However, small-bodied people such as the Hadza and Kung San do not experience high mortality rates (6). It is possible that all these hypotheses are not mutually exclusive and could be evaluated in concert (7).
Physiology and Endocrinology Of Pygmies’ Short Stature Human Pygmies are defined as having an average male height C)
GH receptor
Bozzola, 2009 (21)
Polymorphism exon 8 (IVS7 –9 G > A)
GH receptor
Bozzola, 2009 (21)
Polymorphism exon 10 (p.(Ile544Leu))
GH receptor
Bozzola, 2009 (21)
Table 2. Genetic variability in the GH/IGF-I axis of Pygmies.
populations (20). The authors speculated that the alteration noted may be in linkage disequilibrium with an effective mutation responsible for changes in the GHR of Pygmies, most likely in the regulatory regions of the gene. However, these findings were not confirmed in our more recent DNA sequencing analysis of the GHR gene of Babinga Pygmies of Cameroon. In fact, in June 2006, an expedition organized by our research team reached an ethnic group of Pygmies, called the Babingas, living at the Dja and Lobo reserve, in Southeast Cameroon (Figure 3). Babingas are a large group of Pygmies who live near the boundaries of the Central African Republic, Gabon and Congo in the peripheral forest areas. They have negligible contact with neighbouring Bantu farmers, a population of normal stature. Figure 3: Map of Cameroon (from: geography.about.com). Drawn rounded in red is the area inhabited by Baka Pygmies and Bantu studied during our expedition in 2006.
In the study we enrolled Pygmy subjects and sympatric African Bantu farmers, without any signs of malnutrition, following standard clinical examination. According to previous studies, we found that the basal levels of serum GH were within the normal range and not significantly different in the two groups, while serum GHBP and IGF-I values were significantly reduced in Pygmies. We evaluated the expression
of both GH and GHR genes in peripheral blood cells obtained from the Babinga Pygmy and the sympatric Bantu adults. GHR gene expression was significantly and markedly lower (8 fold) in Pygmies than in Bantu as was the expression level of the GH gene, but to a lesser extent (1.8 less in Pygmies than in Bantu) (Figure 4) (21). However, reduced levels of GHR gene expression were not associated with sequence variants of the gene encoding GHR nor were there variants in the promoter region. Furthermore, the prevalence of the combination of GHR gene polymorphisms was similar in the two groups and haplotype blocks were not found. Therefore, we did not identify, at the genetic level, any variants that could potentially explain the decreased expression of the gene itself. Therefore, we suggest epigenetic or epistatic effects on GHR gene expression. Epigenetic factors that may modify gene expression include diet-related effects. For example, reduced expression of the GHR gene due to the presence of saturated fatty acids via chromatin remodelling has been demonstrated by Thimmarayapp et al (22).
Figure 4. 4 Gene expression values (arbitrary units) of GH (white bars) and GHR (shaded bars) in Babinga Pygmies (21). * p
