Phylogenetic Analysis of the Evolution of Lactose Digestion in Adults

In most of the world’s population the ability to digest lactose declines sharply after infancy. High lactose digestion capacity in adults is common only in populations of European and circumMediterranean origin and is thought to be an evolutionary adaptation to millennia of drinking milk from domestic livestock. Milk can also be consumed in a processed form, such as cheese or soured milk, which has a reduced lactose content. Two other selective pressures for drinking fresh milk with a high lactose content have been proposed: promotion of calcium uptake in highlatitude populations prone to vitaminD deficiency and maintenance of water and electrolytes in the body in highly arid environments. These three hypotheses are all supported by the geographic distribution of high lactose digestion capacity in adults. However, the relationships between environmental variables and adult lactose digestion capacity are highly confounded by the shared ancestry of many populations whose lactose digestion capacity has been tested. The three hypotheses for the evolution of high adult lactose digestion capacity are tested here using a comparative method of analysis that takes the problem of phylogenetic confounding into account. This analysis supports the hypothesis that high adult lactose digestion capacity is an adaptation to dairying but does not support the hypotheses that lactose digestion capacity is additionally selected for either at high latitudes or in highly arid environments. Furthermore, methods using maximum likelihood are used to show that the evolution of milking preceded the evolution of high lactose digestion. The ability to digest lactose in adults is a genetic polymorphism inherited as a dominant genetic trait (Sahi et al. 1973; Johnson et al. 1977; RansomeKuti et al. 1975; Metneki et al. 1984). This trait is common in a few of the world’s populations. The physiological cause of high lactose digestion capacity (LDC) in adulthood is the retention of high levels of lactase in the small intestine beyond infancy (lactase persistence), which contrasts with the standard mammalian developmental pattern of a steep decline in small intestine lactose levels after infancy (Flatz 1987). The LDC of over 20,000 individuals worldwide has been tested. High frequencies ( 70%) of adults with high LDC are found in northern Europeans and 1 Department of Anthropology, University College London, Gower Street, London WC1E 6BT, England. HB_5-6_FINAL.indb 597 5/3/2010 12:28:34 PM 598 / holden and mace their descendants in North America and Australia and among some African pastoralist groups thought to have originated in North or East Africa. Intermediate frequencies (30–70%) of adults with high LDC are found around the Mediterranean, the Middle East, and in central and south Asia. Regions whose adult populations predominantly have low LDC include much of subSaharan Africa, east and southeast Asia, and the native populations of the Americas and Oceania. Patchy sampling in much of subSaharan Africa and in southern and central Asia necessitates caution in our overview of these areas, particularly because the distribution of adult LDC in these regions appears to be locally variable and complex. Selective Pressures for Drinking Milk There are three major hypotheses for the evolution of high adult LDC. The first hypothesis was independently proposed by Simoons (1969, 1970) and McCracken (1971). They observed that in regions where milk was not normally consumed until recently, adults mostly have a low capacity to digest lactose. Therefore it was hypothesized that lactase persistence in adulthood is an adaptation to millennia of pastoralism and milk consumption, a theory known as the culturehistorical hypothesis (Simoons 1970a). This is a coevolutionary theory in which selection of a genetic trait is influenced by the cultural environment, the herding and milking of livestock. According to this hypothesis, the capacity to digest lactose has a selective advantage in adults in pastoralist populations. Individuals with a high LDC are able to derive a nutritional benefit from the lactose in milk, which is not available to individuals with low LDC. Individuals with low LDC may also suffer from symptoms of lactose intolerance when they consume fresh milk, including abdominal discomfort, flatulence, and diarrhea. It has been suggested that, because of these symptoms, milk could be nutritionally detrimental to individuals with low LDC, although this suggestion has been much debated (Scrimshaw and Murray 1988). Populations that keep livestock but do not milk them, for example, populations in China and southeast Asia and parts of subSaharan Africa (Murdock 1967; Simoons 1970), would not be expected to have evolved high adult LDC according to the culturehistorical hypothesis (Simoons 1979). The other two hypotheses refer specifically to the consumption of fresh milk. Milk is often processed into dairy products, such as cheese and yogurt, which have a reduced lactose content. Two specific selective advantages to drinking fresh milk, with a high lactose content, have been proposed. Flatz and Rotthauwe (1973) suggested that in highlatitude environments, where sunshine is limited, humans are at risk of vitamin D deficiency and rickets. The lactose in fresh milk, like vitamin D, promotes the uptake of calcium, also present in milk. This hypothesis could explain the high frequency of lactose digesters in northern European populations. Durham (1991) has used this hypothesis to explain the difference between northern Europe, where fresh milk is consumed in quantity and most adults have high LDC, and the Mediterranean, where milk is mostly eaten as cheese and the population has predominantly low LDC. HB_5-6_FINAL.indb 598 5/3/2010 12:28:34 PM Evolution of Lactose Digestion / 599 The third hypothesis, proposed by Cook and AlTorki (1975) and Cook (1978), states that in highly arid environments the water content of fresh milk increases the survival chances of lactosedigesting milk drinkers among desertdwelling nomadic pastoralists and also that diarrhea and consequent water depletion in lactoseintolerant members of the group cause selection against maldigesters. This hypothesis is supported by the high frequencies of adults with the LDC observed in pastoralist groups in hot areas, for example, the Middle East and North Africa, including the Bedouin, the Tuareg, and the Fulani (Table 1). The evolution of adult lactase persistence has been modeled several times. Bodmer and CavalliSforza (1976) estimated that a selection coefficient of 0.04 would be necessary for high LDC to increase from an initial prevalence of 0.001% to the levels observed today in northern European populations (estimated frequency of 0.5) within 290 generations (9000 years). If the initial frequency of the lactase persistence gene were 1.0%, a selection coefficient of only 0.015 would be required. This time scale is realistic for the Middle East, where livestock were first domesticated around 8000–7000 B.C. (CluttonBrock 1987). Flatz (1987) estimated that for the gene to reach contemporary European levels in the 3500 years or less since the first known domestic livestock in northern Europe, starting from an initial frequency of 0.005%, a higher selection coefficient of between 3% and 7% would be required. More recently, attempts have been made to model the coevolution of a gene for lactase persistence and the cultural trait of milk drinking. Aoki (1986) estimated that for the selection of the gene for lactase persistence to increase from an initial prevalence of 0.05% to the prevalence observed in northern Europe today (estimated gene frequency of 0.7) within the time available since the advent of dairying (6000 years ago) and with an effective population size of 500, the selection coefficient must have been greater than 5%. Feldman and CavalliSforza (1989) also found that a selection coefficient of greater than 5% was necessary for a gene frequency of 0.70 to be reached in 6000 years. However, in these dualinheritance coevolutionary models milk drinking is a cultural trait with a low initial frequency whose selection coefficient depends on the prevalence of the lactase persistence gene. The ethnographic evidence does not support this assumption, insofar as milk consumption apparently has been universally adopted by populations with predominantly low LDC, for example, the Mongols, the Herero, the Nuer, and the Dinka. Milkbased pastoralism may be the best means of subsistence, particularly in dry, marginal environments, even for lactose nondigesters. Milk processing and the consumption of fresh milk in only small quantities are cultural and behavioral means by which many lactose malabsorbers manage to consume milk products without suffering the symptoms of lactose intolerance. After milkbased pastoralism had been adopted as a means of subsistence, high LDC would have enabled adults to consume more fresh milk and to derive a nutritional benefit from the lactose component of fresh milk, and so be selected for. The initial frequency of the cultural trait of milk consumption may therefore be virtually 100%, which could reduce the selection coefficient required HB_5-6_FINAL.indb 599 5/3/2010 12:28:34 PM 600 / holden and mace Ta bl e 1. D at a U se d in th e A na ly si s Pa st or al is m a s P ro po rt io n To ta l N um be r N um be r of G lo ba l S ol ar of T ot al of I nd iv id ua ls F re qu en cy o f Po pu la ti on a nd D ry M on th s R ad ia ti on Su bs is te nc e Te st ed in E ac h L ow L D C E th no gr ap hi c A tl as C od e pe r Ye ar (k ca l/ cm /y r) A ct iv it y (% ) Po pu la ti on (% ) R ef er en ce A pa ch e (N h1 7) 12 16 2 0 22 10 0 Jo hn so n et a l. (1 97 8) A us tr al ia n A bo ri gi ne s a 12 16 7 0 45 84 B ra nd e t a l. (1 98 3) B ag ga ra ( H ab ba ni a) ( C b1 3) 10 17 4 50 .5 19 53 B ay ou m i e t a l. (1 98 1) B ag ga ra ( M es si ri a) ( C b1 5) 10 17 4 70 .5 20 60 B ay ou m i e t a l. (1 98 1) B ed ou in ( Jo rd an ia n (C j2 ) 10 16 2 80 .5 16 2 24 H ija ki e t a l. (1 98 3) B ed ou in ( Sa ud i) ( C j5 ) 12 19 2 93 35 17 C oo k an d A lTo rk i ( 19 75 ), D is sa ny ak e et