- Email: [email protected]
EVOLUTION OF LACTASE PERSISTENCE
493
Estimated numbers of Down syndrome patients older than 40 and 50 years in Netherlands, 1990-2025.
syndrome from 40 years onward,5 especially from the early 50s onwards.6 Between 1990 and 2010 the number of Down syndrome patients older than 40 is expected to increase by about 75% but the number older than 50 will rise by about 200%. Hospitals caring for the mentally retarded can expect an increase in numbers of patients with Down syndrome and an increase in dementia in this
population. Department of Surgical Pathology, Leyenburg Hospital, 2545 CH The Hague, Netherlands
J. W. STEFFELAAR
Hooge Burch Institute for the Mentally Retarded,
H. M. EVENHUIS
Zwammerdam 1. Hustinx TWF, Scheres
JMJC, Geraedts JPM, v Elteren P. Het syndroom van Down in Nederland. Tydschr Kindergeneesk 1986; 54: 101-06. 2. Dupont A, Vaeth M, Videbech P. Mortality and life expectancy of Down’s syndrome in Denmark J Ment Defic Res 1986; 30: 111-20. 3. Baird PA, Sadovnick AD. Life expectancy in Down Syndrome. J Pediatr 1987; 110: 849-54. 4. Malone Q. Mortality and survival of the Down’s syndrome population m Western Australia. J Ment Defic Res 1988; 32: 59-65. 5. Thase ME, Liss L, Smeltzer D, Meloon J. Clinical evaluation of dementia in down’s syndrome a preliminary report. J Ment Defic Res 1982; 26: 239-44. 6. Dalton AJ, Crapper-McLachlan DR. Clinical expression of Alzheimer’s disease in Down’s syndrome. Psychiatr Clin N Am 1986; 9: 659-70.
EVOLUTION OF LACTASE PERSISTENCE
SIR,-Dr Cook (Oct 29,
p
1029) speculates that the high lactase activity in
frequency of adults with persistent intestinal dairying ethnic groups may have resulted
from lamarckian evolution driven by the dietary presence of lactose. We believe that the evidence best fits a traditional darwinian interpretation. Lactase-persistent adults are found, at low frequency, in many populations in which adults do not drink fresh milk. As summarised by McCracken,’ tolerant adults are found in Chinese, Bantu, and Thai populations, groups generally characterised as lactasedeficient. This is not surprising. Persistence of high lactase activity into adulthood probably results from mutations which disrupt the normal regulation of a lactase gene.2 It is thus likely that lactase production in adulthood represents loss, not gain, of genetic function. Mutations causing lactase persistence might occur at a rate of 4 x 10-6 per gamete, the mean mutation rate calculated by Stevenson and Kerrfor deleterious alleles in man. Assuming an initial population frequency of zero and no selection against the mutant allele, such a mutation rate would result in a population frequency of 1-0% for the allele for lactase persistence after 12 500
generations. In the absence of lactose in the adult diet, one would expect that the cost of maintaining the allele would be the material and energy
needed to synthesise and transport the enzyme. Slight selection for the allele might result from nutritional benefit to carrier children who could continue to nurse beyond the age when lactase synthesis would have normally been repressed. On balance, an assumption of selective neutrality before the advent of dairying is not unreasonable. The question then becomes one of how great the selective forces favouring lactase persistence would be after the institution of dairying. Lactase-negative adults could gain most of the caloric benefit of milk consumption by eating lactose-reduced dairy products such as butter, curd-derived cheeses, or fermented milk products in which most of the lactose has been converted to benign lactate. While the advantage of persistent lactose metabolism per se may be minimal (but see McCracken’), significant secondary selective benefit may result, for example, by the ability to use raw milk as a source of dietary calcium. Whether or not lactose improves calcium absorption is controversial. 4.5 However, an association of postmenopausal osteoporosis with lactase deficiency is believed to result from a lifelong pattern of low milk consumption by lactase-deficient adults 6 Also, lactation generally results in highly negative calcium balance. Irvinlt felt that such stress may cause considerable maternal morbidity in the absence of adequate nutrition. A hypothesis that the selective advantage of lactase persistence results from improved calcium nutrition, especially for lactating females, may therefore have merit. Regardless of its mode of action, even very weak selection should produce dramatic increases in the frequency of adult lactase persistence because the mutation for persistence acts as an advantageous dominant allele. For example, with an initial allele frequency of 10% (established by mutation) and a selection coefficient of 0-02, roughly half of all individuals in a dairying population would be expected to be lactase persistent after 200 generations. This very weak level of selection requires only that lactase-persistent individuals produce 100 surviving offspring for every 98 produced by the lactase negatives. Higher selection coefficients would result in proportionate decreases in the time required to effect this change. This result, which follows from a strictly darwinian interpretation, is consistent with both the limited data available on population frequencies of lactase persistence and the timescale for the development of dairying. We see no need to invoke a non-darwinian scheme to explain the present extent of lactase persistence. Department of Biology, College of William and Mary, Williamsburg, Virginia 23185, USA; and Genetics Program, Eastern Virginia Medical School, Norfolk, Virginia 1. McCracken RD. Lactase
deficiency,
STANTON F. HOEGERMAN RUSSELL A. SCHENCK an
example of dietary evolution. Curr Anthrop
1971, 12: 479-517. 2. Potter J, Ho M-W, Bolton H, et al. Human lactase and the molecular basis of lactase persistence. Biochem Genet 1985; 23: 423-39.
AC, Kerr CB. On the distribution of frequencies of mutation in genes determining harmful traits in man. Mutat Res 1967; 4: 339-52. 4. Irving JT. Calcium and phosphorus metabolism. New York: Academic Press, 1973. 5. Tremaine WJ, Newcomer AD, Riggs BL, McGill DB. Calcium absorption from milk in lactase-deficient and lactase-sufficient adults. Dig Dis Sci 1986; 31: 376-78. 6. Birge SJ, Keutmann HT, Cuatrecasas P, Whedon GD. Osteoporosis, intestinal lactase deficiency and low dietary calcium intake. N Engl J Med 1967; 276: 495-98. 3. Stevenson
NASOPHARYNGEAL OXYGEN IN CHILDREN
SIR,-Dr Shann and colleagues (Nov 25, p 1238) believe that given by continuous insufflation of the pharynx (CIP) will improve the care of children in underdeveloped countries with severe respiratory tract infections. But this is unlikely to be the case. The advantage gained by the more efficient delivery of oxygen by CIP is offset by the fact that the method is safe only if, as Shann et al say, "the tip of the catheter is placed in the pharynx, the catheter is kept clean, and care is taken to avoid excessive flow rates of oxygen". Our experience is that considerable expertise is required to place catheters correctly in the oropharynx and to manage CIP.’ These skills and the equipment (low-range flow meters and humidifiers) are not likely to be available where they are needed most. oxygen
Estimated numbers of Down syndrome patients older than 40 and 50 years in Netherlands, 1990-2025.
syndrome from 40 years onward,5 especially from the early 50s onwards.6 Between 1990 and 2010 the number of Down syndrome patients older than 40 is expected to increase by about 75% but the number older than 50 will rise by about 200%. Hospitals caring for the mentally retarded can expect an increase in numbers of patients with Down syndrome and an increase in dementia in this
population. Department of Surgical Pathology, Leyenburg Hospital, 2545 CH The Hague, Netherlands
J. W. STEFFELAAR
Hooge Burch Institute for the Mentally Retarded,
H. M. EVENHUIS
Zwammerdam 1. Hustinx TWF, Scheres
JMJC, Geraedts JPM, v Elteren P. Het syndroom van Down in Nederland. Tydschr Kindergeneesk 1986; 54: 101-06. 2. Dupont A, Vaeth M, Videbech P. Mortality and life expectancy of Down’s syndrome in Denmark J Ment Defic Res 1986; 30: 111-20. 3. Baird PA, Sadovnick AD. Life expectancy in Down Syndrome. J Pediatr 1987; 110: 849-54. 4. Malone Q. Mortality and survival of the Down’s syndrome population m Western Australia. J Ment Defic Res 1988; 32: 59-65. 5. Thase ME, Liss L, Smeltzer D, Meloon J. Clinical evaluation of dementia in down’s syndrome a preliminary report. J Ment Defic Res 1982; 26: 239-44. 6. Dalton AJ, Crapper-McLachlan DR. Clinical expression of Alzheimer’s disease in Down’s syndrome. Psychiatr Clin N Am 1986; 9: 659-70.
EVOLUTION OF LACTASE PERSISTENCE
SIR,-Dr Cook (Oct 29,
p
1029) speculates that the high lactase activity in
frequency of adults with persistent intestinal dairying ethnic groups may have resulted
from lamarckian evolution driven by the dietary presence of lactose. We believe that the evidence best fits a traditional darwinian interpretation. Lactase-persistent adults are found, at low frequency, in many populations in which adults do not drink fresh milk. As summarised by McCracken,’ tolerant adults are found in Chinese, Bantu, and Thai populations, groups generally characterised as lactasedeficient. This is not surprising. Persistence of high lactase activity into adulthood probably results from mutations which disrupt the normal regulation of a lactase gene.2 It is thus likely that lactase production in adulthood represents loss, not gain, of genetic function. Mutations causing lactase persistence might occur at a rate of 4 x 10-6 per gamete, the mean mutation rate calculated by Stevenson and Kerrfor deleterious alleles in man. Assuming an initial population frequency of zero and no selection against the mutant allele, such a mutation rate would result in a population frequency of 1-0% for the allele for lactase persistence after 12 500
generations. In the absence of lactose in the adult diet, one would expect that the cost of maintaining the allele would be the material and energy
needed to synthesise and transport the enzyme. Slight selection for the allele might result from nutritional benefit to carrier children who could continue to nurse beyond the age when lactase synthesis would have normally been repressed. On balance, an assumption of selective neutrality before the advent of dairying is not unreasonable. The question then becomes one of how great the selective forces favouring lactase persistence would be after the institution of dairying. Lactase-negative adults could gain most of the caloric benefit of milk consumption by eating lactose-reduced dairy products such as butter, curd-derived cheeses, or fermented milk products in which most of the lactose has been converted to benign lactate. While the advantage of persistent lactose metabolism per se may be minimal (but see McCracken’), significant secondary selective benefit may result, for example, by the ability to use raw milk as a source of dietary calcium. Whether or not lactose improves calcium absorption is controversial. 4.5 However, an association of postmenopausal osteoporosis with lactase deficiency is believed to result from a lifelong pattern of low milk consumption by lactase-deficient adults 6 Also, lactation generally results in highly negative calcium balance. Irvinlt felt that such stress may cause considerable maternal morbidity in the absence of adequate nutrition. A hypothesis that the selective advantage of lactase persistence results from improved calcium nutrition, especially for lactating females, may therefore have merit. Regardless of its mode of action, even very weak selection should produce dramatic increases in the frequency of adult lactase persistence because the mutation for persistence acts as an advantageous dominant allele. For example, with an initial allele frequency of 10% (established by mutation) and a selection coefficient of 0-02, roughly half of all individuals in a dairying population would be expected to be lactase persistent after 200 generations. This very weak level of selection requires only that lactase-persistent individuals produce 100 surviving offspring for every 98 produced by the lactase negatives. Higher selection coefficients would result in proportionate decreases in the time required to effect this change. This result, which follows from a strictly darwinian interpretation, is consistent with both the limited data available on population frequencies of lactase persistence and the timescale for the development of dairying. We see no need to invoke a non-darwinian scheme to explain the present extent of lactase persistence. Department of Biology, College of William and Mary, Williamsburg, Virginia 23185, USA; and Genetics Program, Eastern Virginia Medical School, Norfolk, Virginia 1. McCracken RD. Lactase
deficiency,
STANTON F. HOEGERMAN RUSSELL A. SCHENCK an
example of dietary evolution. Curr Anthrop
1971, 12: 479-517. 2. Potter J, Ho M-W, Bolton H, et al. Human lactase and the molecular basis of lactase persistence. Biochem Genet 1985; 23: 423-39.
AC, Kerr CB. On the distribution of frequencies of mutation in genes determining harmful traits in man. Mutat Res 1967; 4: 339-52. 4. Irving JT. Calcium and phosphorus metabolism. New York: Academic Press, 1973. 5. Tremaine WJ, Newcomer AD, Riggs BL, McGill DB. Calcium absorption from milk in lactase-deficient and lactase-sufficient adults. Dig Dis Sci 1986; 31: 376-78. 6. Birge SJ, Keutmann HT, Cuatrecasas P, Whedon GD. Osteoporosis, intestinal lactase deficiency and low dietary calcium intake. N Engl J Med 1967; 276: 495-98. 3. Stevenson
NASOPHARYNGEAL OXYGEN IN CHILDREN
SIR,-Dr Shann and colleagues (Nov 25, p 1238) believe that given by continuous insufflation of the pharynx (CIP) will improve the care of children in underdeveloped countries with severe respiratory tract infections. But this is unlikely to be the case. The advantage gained by the more efficient delivery of oxygen by CIP is offset by the fact that the method is safe only if, as Shann et al say, "the tip of the catheter is placed in the pharynx, the catheter is kept clean, and care is taken to avoid excessive flow rates of oxygen". Our experience is that considerable expertise is required to place catheters correctly in the oropharynx and to manage CIP.’ These skills and the equipment (low-range flow meters and humidifiers) are not likely to be available where they are needed most. oxygen