Testing life history theory in a contemporary African population
Meij, J.J.
Citation
Meij, J. J. (2008, February 21). Testing life history theory in a contemporary African population. Retrieved from https://hdl.handle.net/1887/12615
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden
Downloaded from: https://hdl.handle.net/1887/12615
Note: To cite this publication please use the final published version (if applicable).
Chapter 1
General introduction
9
Map 1. Republic of Ghana
Introduction
Ample experimental data support the notion that investments in fitness trade- off with investments in body maintenance. The study of life history regula- tion in humans does not allow for experimentation, but observations of extraordinary phenotypes in specific environments have provided arguments for the notion that human life histories are under similar, genetically encod- ed control.Virtually all human studies on the topic performed so far, used his- torical cohorts as a source, in part because of the relative ease with which this type of data can be retrieved. Most of these observations were of people that lived under relatively adverse conditions, mimicking the environment in which our population genome has taken shape. These studies have scientific limitations, as other key characteristics of the life histories are scarce and access to biomaterials is virtually absent. In contrast, almost all observations of life history regulation in contemporary populations fail from an evolution- ary point of view. The subjects under study are exposed to a modern, afflu- ent environment in which fertility is under medical control and mortality pat- terns have changed dramatically, as infection and external causes have disap- peared as leading causes of death. It is for these reasons that we have started a unique research project in the Upper East Region of Ghana, a remote part of Africa, to study determinants of early and late life survival, fertility and fit- ness under adverse conditions. This scientific endeavor also allowed for col- lecting more detailed phenotypes and assessment of biomaterials, the ulti- mate aim being, to understand the regulations of human life histories on a bio molecular level. This first chapter provides a very brief introduction to the underlying theories in general and an introduction to the study area more specifically.
Life histories
Evolutionary life history theory argues that ageing is an inevitable conse- quence of fitness being maximized in a specific environmental niche [1]. In order for the species to survive, investments in fitness, passing genes into subsequent generations, proceed at the cost of investments in maintenance and subsequently leads to a deterioration of the body at older age. This con- stant tradeoff between investments in fitness and body maintenance, amidst the environmental conditions to which the species is exposed, results in sur- vival probabilities of individuals that are not higher than necessary for repro- ductive success. Individual life histories are tailored by increasing probabili- ties of disease and death. Species that have maximized reproductive success at the cost of their individual lifespan are far more likely to survive compared to species that have maximized lifespan but are less reproductively success- ful.
11
As early as 1789, some sixty years before Darwin wrote “The origin of species by means of natural selection”[2], Malthus proposed that all creatures (animals and plants alike) are in constant interaction with the environment to optimize the make up of their own species [3]. Malthus applied this idea to both the animal and plant kingdom. In general, he stated that: ‘many more individuals of a species are born than can possibly survive. As a consequence, there is a constant recurring struggle for existence. The variation of a species that is profitable to itself, will have a better chance of surviving, and will thus naturally be selected. Therefore, any selected variation will tend to propagate its new and modified form’[3]. In 1801, Lamarck suggested that species are continuously changing over time and argued that individual adaptations to the environment were imprinted and passed into the next generations [4].
This idea was for a long time thought to be unrealistic, the force of selection being a superior explanation for the adaptation of the species to its environ- ment. Today, the ideas of Lamarck are ‘en vogue’ again as epigenetic control of gene expression provides a sufficient bio molecular mechanism of how adaptive responses can be passed into the next generation [5]. Some years after Lamarck, in 1813, Wells observed that mulattos and black-skinned peo- ple were immune to diseases to which white people were highly susceptible [6]. He postulated that nature selected out races depending on the place they lived. Although Wells did not integrate his observations into theory, amongst others he paved way to the theory of natural selection. Although the theory of evolution and evolutionary selection is still disputed among biologists [7], anthropologists [8, 9], theologians and philosophers [10,11], natural selection as the key mechanism for shaping individual life histories cannot be ignored.
Disposable soma
Ageing is the result of a random accumulation of permanent damage to mol- ecules, cells and tissues [12]. This accumulation primarily results from a con- tinuous, random exposure to, amongst others, reactive metabolites, infectious diseases, accidents, famine, and extreme temperatures. The body has the abil- ity to repair some of the damage and to maintain its function. As investments in repair and maintenance occur with a cost to fitness, these investments will always be less than is sufficient to prevent the body from deteriorating. The body is thus disposed to allow the genetic lineage to proceed.
Fitness, the success of a genetic lineage, is dependent on fertility per se, and maintenance of the body, in order to survive up to reproductive age. Limited resources have to be divided between body maintenance and fertility. This notion is also described by the r/K-selection theory as proposed by MacArthur and Wilson [13]. The symbols r and K refer to two ends of a con- tinuum, where a compensatory exchange occurs between investment in fer-
tility (r-selection) and in body maintenance (K-selection). Selection for high- er investments in maintenance, allowing for longer lifespans, is only success- ful when extrinsic mortality is low enough allowing for reproductive efforts to reduce. For instance, wild mice cannot allow higher investment in mainte- nance since in their natural environment, exposed to high mortality risks from external causes, investments in reproduction are being maximized.
Depending on the specific environment, the ‘evolutionary niche’, each species will have optimized investments in body maintenance up to repro- ductive age and investments in reproductive success, to increase the fitness of the species (Figure 1) [14].
Figure 1. Schematic diagram of the trade off between investments in maintenance (projected as life years) and fitness (projected as number of progeny). (adapted from Kirkwood, 1999).
The past two decades have produced ample experimental evidence for life history trade-offs within species. Experiments with the fruit fly, Drosophila melanogaster, proved the general existence of trade-offs between longevity and reproduction, for both females and males [15,16]. A selection regimen that favored flies that had retained fertility at later ages resulted in populations with increased life spans, reduced fertility early in life and enhanced resistance to a variety of stresses.This suggested that the mechanisms underlying the increase in lifespan involve greater investments in somatic durability. Direct selection for longevity, by exploiting the dependence of the lifespan of fruit flies on temperature, also produced long- lived populations with significantly reduced fertility, underpinning a genetic
13
cause for the trade-off [16]. Similar trade-offs have been described for the worm Caenorhabditis elegans. A series of point mutations in the insulin- signaling pathway - regulating metabolism, stress resistance and cell growth - are associated with increases in lifespan of up to 200%, although at the cost of reproductive success [17]. The best evidence for the existence of a trade- off between reproduction and longevity, however, is provided by experiments in which germ line precursor cells are removed resulting in a marked increase of the worm’s lifespan [18].
Few would accept that the experimental work in fruit flies and worms could also apply for humans, but in recent years several researchers have investi- gated this tradeoff between longevity and reproductive success in human populations. Previously, our group has shown that there is a clear association between longevity and reproductive success, using a historical data set from the British aristocracy [19]. We have shown that the number of progeny was small when women died young, increased with an incremental age of death, but decreased again in women who died at an age of 80 years and over. The association was most significant in the pre-1700 period whereas it disappeared in later birth cohorts. This fading of a tradeoff between longevity and reproductive success suggests that the demographic and epidemiological transition, that started among the aristocracy around 1700, may account for the disappearance of the negative correlation.
Lycett, Dunbar and Voland [20] examined the same relationship in The Krummhorn region (North-West Germany) in the period 1720 – 1870. They found the association between longevity and reproductive success to be stronger with increasing poverty and successfully argued that their results, in combination with closer inspection of the data among the British aristocracy, suggested that the trade-off between reproduction and longevity is context contingent. The tradeoff is most apparent under ‘natural conditions’, i.e.
when mortality from extrinsic causes is high. These two reports on the relationship between longevity and reproduction success have been confirmed in various other populations [21,22,23]. However, some studies have not demonstrated a negative association between fertility and survival.
Costa et al found no relationship between successful ageing and reduced reproduction in 88 centenarian women in Calabria, Italy, during the 20th century [24]. Moreover, Le Bourg also found no tradeoff in a group of French Canadians in the 17th and 18th century [25].
Role of immunity
Here we propose a molecular mechanism that could underlie the trade-off between reproductive success and longevity, the obvious candidate being
immunity [26]. Amongst others, the adverse conditions in our natural habitat necessitate large investments in an adequate immune system to fight abundant infections and, therefore, reach reproductive age. Previously, we have studied the levels of two major regulatory cytokines, interleukin-10 (IL- 10) and tumor necrosis factor (TNF), in first degree relatives of patients who suffered meningococcal disease, an infection that is widely present in Africa and occasionally surfaces in developed countries [27]. Cytokines are signaling molecules for cell–cell interactions, and include compounds, such as TNF, which initiate an inflammatory response to fight infection, and regulatory signals, such as IL-10, to switch off the inflammatory response and prevent collateral damage after the infection has been overcome.
Cytokine activity has been shown to be under tight genetic control and we therefore assumed that families of those patients who had died would have a distinct pattern of cytokine activity. Almost without exception, the level of pro-inflammatory TNF in all of these fatal cases was low, and the level of the anti-inflammatory IL-10 was high [28]. The interpretation of these results was, that subjects with an innate propensity towards anti-inflammatory responses are at an increased risk of death from infection.
In contrast with fighting infection, which requires a strong inflammatory host response, reproductive success depends on a tolerant immune response.
About half of a baby’s tissue antigens have paternal origin, so at the fetal–maternal interface, immune reactions must be suppressed to allow pregnancy to proceed. Cytokine profiles of women with impaired fertility, as defined by having at least three consecutive spontaneous abortions, were compared with the profiles of women of normal fecundity [29]. Reproductive success was associated with a tolerant profile, low TNF-α and high IL-10, whereas an inflammatory profile was associated with habitual abortion. The probability of normal fecundity increased up to 16-fold when the women’s cytokine levels were characterized by high anti-inflammatory and low pro- inflammatory profiles.
These data on cytokine profiles help to elucidate two phenomena. First, they can explain why British aristocrats, who lived longer, were less likely to have successful pregnancies. Their innate immune system favored resistance to infection but at the same time prevented pregnancy from proceeding; a trade- off that was even stronger in times when the environmental conditions were relatively poor. Second, it explains why a genotype associated with impaired fertility might have persisted in spite of its obvious disadvantage with regard to evolutionary fitness. Selection for resistance to infection is traded against selection for fertility, resulting in a compromise that is optimal for the fitness of the species in a specific environment.
15
Despite its protective role in infection, inflammation is potentially harmful;
for instance, strong pro-inflammatory responses can cause tissue damage at the site of infection. Although humans are programmed to resist infection, in affluent countries the burden of disease has now shifted away from infectious diseases towards chronic diseases that are typically expressed in old age.
Accordingly, fatal infections still account for the majority of deaths in less- developed parts of the world, especially at younger ages, but cardiovascular disease has become the leading cause of mortality in ageing populations, accounting for 30% of all deaths worldwide each year. There is clear evidence that inflammation contributes to the development of cardiovascular disease [30]. For example, levels of C-reactive protein, a marker of inflammation, have been associated with coronary artery disease, angina and infarction. Moreover, results from population-based studies have demonstrated that increased levels of markers of inflammation, such as cytokines, adhesion molecules and acute phase reactants, are associated with cardiovascular events. Because our immune system has evolved under the constant attack of pathogens, we are evolutionarily programmed for an inflammatory response to resist infection. In old age, however, the protective effect of this inflammatory response trades off with the increased risk of death from cardiovascular events, reducing life expectancy. Besides cardio- vascular disease, inflammation increases the susceptibility and severity of various other chronic diseases.
Aim of the thesis
In this thesis we aim to test the hypothesis that reproductive success trades off with (early) survival in a contemporary population, validating the pre- vious findings in historic populations [19,20,23]. For reasons that are outlined above, this test can only be performed in a population that is still exposed to high mortality risk from extrinsic causes and, from an epidemiological point of view, is still in an early stage of transition. After careful analysis of three different areas in Africa, we have chosen the remote Garu-Tempane district in the Upper-East Region, Ghana as the research area.
This area is one of the least developed areas in Ghana. The socio-economic conditions resembling more of the less developed neighboring country Burkina Faso than of southern Ghana. This area was able to be accessed quickly because of previous research activities in the area [31] and due to excellent relations with the Ghana Health Service and Regional Healthcare Authorities.
Setup of the studies
The studies reported here result from an idea, mutually proposed by the promotor and author of this thesis, to test for evolutionary trade-offs in
contemporary human populations. The idea was not only to expand on the analyses of historical datasets, but also, to create a platform for testing biological hypotheses regarding the determinants of health and disease in adverse and affluent societies. This resulted in starting the “Africa Research Project” in 2002, of which the author of this thesis was appointed project leader. His first task was to identify a research area with the necessary demographic characteristics. To this end several field trips were organized and after careful consideration the Garu-Tempane district area was selected to be the most suitable. Fieldwork started in May 2003, after thorough preparations, and during the six months that followed, the research infra- structure was successfully set up. Offices were located, field staff were recruited, and population registries were installed. Besides the critical role of paper and pencil, ‘modern’ techniques such as GPS-mapping, DNA collection using mouth swabs, and in a later stage cytokine stimulation assays, could successfully be implemented on a population scale. Since then annual follow-up visits have been organized for painstaking assessment of numbers of births, deaths and migration patterns and biological sampling of newborns and new-comers in the area. From the 2004 survey onwards pilot studies were performed to collect anthropomorphic and socio-economical characteristics. During the period, 2004 through 2007, while in Leiden, the results of the initial fieldwork were analyzed and are presented in this thesis.
From the 2005 and 2006 survey onwards, the activities have clearly expanded beyond the scope of this thesis. Funds were granted (NWO Wotro 93-467, Stichting Dioraphte, NWO MAGW 051-14-050) and two additional researchers were appointed. With the launch of LifeSpan (LSHG-CT-2007- 036894), a European network that aims to establish the relationship between early-life events, late-life survival and health, the Africa Research Project has become a critical ‘instrument’ to identify the biological mechanisms that underpin this relationship.
A short introduction to the research area
The Garu-Tempane district is a remote Upper East Region part of the Repu- blic of Ghana (see Map 1, page 10). During the last centuries it has been an alternating part of Togo, and Gold Coast (former Ghana) [32]. Historically, the tribes in this area lived in constant conflict with the ruling Ashanti Kingdom. The Ashanti were intermediary slave traders and recruited their slaves from the tribes of the present day Upper Regions [33,34]. During the process of independence (1957) the people living in the Upper East Region (formerly under UK-trusteeship) chose to be part of Ghana [32], but the difference in economic development between the south and the north is still vast. The average per capita income of the southern regions of Ghana in the
17
year 2002 was 2130 dollars [35]. The International Fund for Agricultural Development has estimated the GDP for the Upper East Region at USD 304 per year [36]. Since the Garu-Tempane district is one of the least developed districts in the Upper East Region, the actual GDP of the research area is even lower.
Map 2. Ghana, Garu-Tempane district and research area(reproduced with kind permis- sion of Dr. J. Ziem, Tamale, Ghana).
The Garu-Tempane District is a densely populated agricultural area (compare: 66 inhabitants per km2 to 43 per km2 for the whole Upper East Region). The research area comprises the southern half of this District (see map 2), measures 375 square kilometer and consists of 36 villages. In total approximately 24,000 individuals live in the area in 2,300 compounds. The area is inhabited by several tribes, the Bimoba (66%), Kusasi (22%), Mamprusi (4%), Busanga (4%), and Jense (1%). A small group of (more nomadic) Fulani (2%) is living in the area as well. Although the Bimoba tribe is by far the largest tribe in the area, they have no ruling power. The area has
18
a semi-Saharan climate with an average temperature of 32º C throughout the year and only one rain season (June – August). The entire area has a low level of organization and no civil registries exist.
The majority of the population farm. The total agricultural process is done by manual labor. Mechanized farming is absent. In the research area some health clinics have been set up recently, but they are not in full service yet. Hospitals and medical services are absent in the area. Vaccination of children was introduced in the early nineties of the previous century. Although not everybody can afford vaccination, at least 50 % of all children below 10 years have been vaccinated at least once. Illiteracy is very high, among adults it is almost complete and among children it is still very high (> 50 %) [37].
Outline
The studies in Part A were carried out to analyze the exact stage of epidemiologic transition of the area. The predominant ethnic group within the research area is the Bimoba tribe, living in the southern part of the Garu- Tempane district. Although there is an impressive study of the neighboring Moba tribe with similar tribe structure and traditions [38], little is known about the Bimoba people [39]. At the time when the research began, hardly any written information about population and family structure was available.
So, to be able to analyze the phenotypic and genetic data, first it was necessary to analyze the structure of the research population, the family structure and reproduction patterns. Chapter 2 is a concise ethnography of the Bimoba. Since the Bimoba tribe is mainly endogamic, consanguinity can become a confounding factor in genetic analysis. Therefore, the actual family ties and (possible) inbreeding within the Bimoba tribe were determined. By analyzing the Y-chromosome, together with the obtained oral pedigree, a genetic pedigree of the population of the FarFar village, a typical village within the area, was able to be drawn. The results of this study are described in Chapter 3. Finally, to establish the actual stage of epidemiologic transition within the region, the current mortality figures (2002-2005) of the population within the region were analyzed. These were compared with the Gross National Product (GNP) of the area and with all other countries in the world.
The results are described in Chapter 4
The second part of the thesis, Part B, consisted of testing the trade-off between (early) survival and reproductive success from different perspectives. Chapter 5 describes the survival rates of children depending on the size of the kindred as an estimate of fecundity among 2.300 women of 25 years and older. By doing so, it was assessed whether the trade-off between survival of the children and the reproduction capacity of the mother was
19
present in this population. The levels of production of pro- and antiinflam- matory cytokines, among different age groups, are compared in Chapter 6.
Both the IL-10 and TNF-α production were assessed and the Ghanaian results were compared with the findings in an affluent society, i.e. The Netherlands. Known variants of the IL-10 promotor were also analyzed.
Arguments for an immunogenetic explanation for the trade-off between (early) survival and reproductive success are discussed. The unique DNA collection provided the opportunity to test other host response mechanisms as well. In Chapter 7 the possible functionality of Caspase-12, an essential protease that plays a crucial role in the inflammatory host response, was test- ed.
Finally, in Chapter 8 the results of the entire research project are summarized and discussed in the broader perspective.
References
1. Stearns SC (1992) The Evolution of Life Histories. Oxford University Press, Oxford.
2. Darwin C (1859) The Origin of Species by Means of Natural Selection Or the Preservation of Favoured Races in the Struggle for Life, John Murray, Albemarle Street W, London (used imprint: 1917).
3. Malthus T (1798) An Essay on the Principle of Population, as it Affects the Future Improvement of Society with Remarks on the Speculations of Mr.
Godwin, M. Condorcet, and Other Writers, Printed for J Johnson, in St.
Paul’s Cathedral-yard London.
4. Lamarck JB (1801) Zoological philosophy: an exposition with regard to the natural history of animals. [transl. from French], (1984) University of Chicago Press, Chicago.
5. Charmantier A, AJ Keyser & DE Promislow (2007) First evidence for heritable variation in cooperative breeding behaviour. Proceedings of the Royal Society 10.1098/rspb.2007.0012 (on line ahead of publication).
6. Wells WC (1813) An Account of a White female, part of whose skin resembles that of a Negro”, Mentioned in C. Darwin (1859) The origin of Species, John Murray Albemarle Street W, London (used imprint: 1917).
7. Duminil J, S Fineschi, A Hampe, P Jordano, D Salvini, et al (2007) Can population genetic structures be predicted from life-history traits? Am Nat.
169(5): 662-72.
8. Claessen H & P Kloos (1978) Evolutie en evolutionisme, Van Gorcum, Assen/Amsterdam.
9. Dobzhansky T (1963) Anthropology and the Natural-Sciences - the Problem of Human-Evolution, Current Anthropology 4:138-139.
10. Dembski W (2002) No Free Lunch. Why specified complexity cannot be purchased without intelligence, Rowman & Littlefield, Lanham, MD
11. Ruse M (2006) The Evolution Creation Struggle, Harvard University Press Cambridge, MA
12. Kirkwood TB, SN Austad (2000) Why do we age? Nature 408:233-8.
13. Macarthur RH & EO Wilson (1967) The Theory of Island Biography, Princeton University Press, Princeton, New Jersey.
21
14. Kirkwood TB (1999) Time of our Lifes. The science of Human Aging, Oxford University Press, New York.
15. Sgro CM., G Geddes, K Fowler & L Padrtridge (2000) Selection on age at reproduction in Drosophila melanogaster: female mating frequency as a correlated response, Evolution Int. J. Org. Evolution 54: 2152-2155.
16. Zwaan B, R Bijlsma & RE Hoekstra (1995) Direct Selection on Life Span in Drosophila-Melanogaster, Evolution 49: 649-659.
17. Arantes-Oliveira N, JR Berman & C Kenyon (2003) Healthy animals with extreme longevity, Science. 302:611.
18. Arantes-Oliveira N, J Apfeld, A Dillin & C Kenyon (2002) Regulation of life span by germ-line stem cells in Caenorhabditis elegans, Science 295:
502-505.
19. Westendorp RGJ, TB Kirkwood (1998) Human longevity at the cost of reproductive success, Nature 396:743-746.
20. Lycett, JE, RI Dunbar & E Voland (2000) Longevity and the costs of reproduction in a historical human population, Proc.Biol.Sci. 267: 31-35.
21. Thomas F, AT Teriokhin, F Renaud, T de Meeus & JF Guegan (2000) Human longevity at the cost of reproductive success: evidence from global data, Journal of Evolutionary Biology 13: 409-414.
22. Smith KR, GP Mineau & LL Bean. (2002) Fertility and post-reproductive longevity, Social Biology 49: 185-205.
23. Doblhammer G (2000) Reproductive history and mortality in later life: A comparative study of England and Wales and Austria, Population Studies 54 169 – 176.
24. Costa MC, F Luzza & R Mattace (2000) Centenarians at no cost of reproductive success, Age and Ageing 29(4): 373-4.
25. Le Bourg E, B Thon, J Legare, B Desjardins & H Charbonneau (1993) Reproductive life of French-Canadians in the 17-18th centuries: a search for a trade-off between early fecundity and longevity, Exp. Gerontol. 28: 217- 232.
26. Westendorp RGJ (2004) Are we becoming less disposable? EMBO Rep.
5: 2-6.
27. Westendorp RGJ, A Langermans, TW Huizinga, AH Elouali, CL Verweij,
et al. (1997) Genetic influence on cytokine production and fatal meningococcal disease, Lancet 349: 170-173.
28. Dissel JT van, P Langevelde & RGJ Westendorp (1998) Anti- inflammatory cytokine profile and mortality in febrile patients, Lancet 351:950-953.
29. Westendorp RGJ, FM van Dunne, TB Kirkwood, FM Helmerhorst &
TWJ Huizinga (2001) Optimising human fertility and survival, Nature medicine 7:873.
30. Libby P, PM Ridker & A Maseri (2002) Inflammation and athero- sclerosis, Circulation 105: 1135-1143.
31. Ziem JB, A Olsen, P Magnussen, J Horton, N Spannbrucker et al (2006) Annual mass treatment with albendazole might eliminate human oesophaostomiasis from endemic focus in northern Ghana, Journal of Tropical Medicine & international Health 11(11): 1759-63.
32. Okyere VN (2000) Ghana, a historical Survey, Vinojab Publications, Accra, pp.166-169.
33. Baden-Powell RSS (1898) The Downfall of Prempeh, a diary of life with the native levy in Ashanti, Methuen & Co, London.
34. Meredith M (2006) The State of Africa; A history of fifty years of independence. The Free Press, London, pp. 17 – 29.
35. UN (2002) Community Database World Bank. Online. (assessed 10 may 2007)
36. van Dunne FM, AJ de Craen, FM Helmerhorst, TWJ Huizinga, RGJ Westendorp (2006) Interleukin-10 promoter polymorphisms in male and female fertility and fecundity, Genes Immun 7(8): 688-92.
37. Ghana Statistical Services (2004) Demographic and Health Survey 2003, Noguchi Institute for Medical Research, Accra.
38. Zwernermann J (1998) Studien zur Kultur der Moba (Nord-Togo), Rűdiger Köppe Verlag, Köln.
39. Assimeng M (1990) Bimoba Sociological Study, University of Ghana, Legon.
23
