Lactase persistence is the continued activity of the enzyme lactase in adulthood. Since lactase's only function is the digestion of lactose in milk, in most mammal species the activity of the enzyme is dramatically reduced after weaning. However in some human populations lactase persistence has recently evolved as an adaptation to the consumption of non-human milk and dairy products beyond infancy. The majority of people around the world remain lactase non-persistent, and consequently are affected by varying degrees of lactose intolerance as adults – though not all genetically lactase non-persistent individuals are noticeably lactose intolerant, and not all lactose intolerant individuals have the lactase non-persistence allele.
Multiple studies indicate that the presence of the two phenotypes "lactase persistent" and "lactase non-persistent (hypolactasia)" is genetically programmed, and that lactase persistence is not necessarily conditioned by the consumption of dairy products after the suckling period.
The lactase persistent phenotype involves high mRNA expression, high lactase activity and thus the ability to digest lactose. On the other hand, the lactase non-persistent phenotype involves low mRNA expression and low lactase activity. The enzyme lactase is encoded by the gene LCT.
Hypolactasia is known to be recessively and autosomally inherited, which means that an individual with the non-persistent phenotype is homozygous and received the two copies of the lactase gene from their parents, who may be homozygous or at least heterozygous. Also, only one active lactase gene is required to be lactase persistent, because lactase persistence is dominant to hypolactasia. Lactase persistence behaves as a dominant trait because half levels of lactase activity are sufficient to show significant digestion of lactose. Cis-acting transcriptional silence of the lactase gene is responsible for the hypolactasia phenotype. Furthermore, studies show that only 8 cases were found where the parents of a child with lactase persistence were both hypolactasic. While a variety of genetic, as well as nutritional factors determine lactase expression, there is no evidence for adaptive alteration of lactase expression within an individual in response to changes in lactose consumption levels. There are two distinct phenotypes of hypolactasia. Phenotype I is characterized by reduced synthesis of precursor LPH while the mechanism of decreased lactase activity in phenotype II is associated with ample precursor synthesis but reduced conversion of the protein to its mature molecular form. The lactase enzyme has two active sites which break down lactose. The first is at Glu1273 and the second is at Glu1749, which separately break down lactose into two separate kinds of molecules.
Two mutations or SNP (single-nucleotide polymorphism) have been associated to lactase expression. It was found that C−13910 (C at position -13910 upstream of the gene LCT) and G−22018 (G at position -22018) are related to lactase non-persistence while the T−13910 and A−22018 are related to lactase persistence. In addition, studies have demonstrated that the lactase gene has a higher expression when T−13910 and A−22018 are present and a lower expression when C−13910 and G−22018 are present. It was also proven that the position -13910 has an enhancer function on the lactase promoter (the promoter facilitates the transcription of the LCT gene). T−13910 is a greater enhancer than C−13910, so it is thought that this mutation is responsible for the differences in lactase expression although there is not enough evidence to prove that lactase persistence is only caused by C−13910→T−13910.
In one study involving a Finnish population, a CT SNP at –14 kb was found in all lactase persistent individuals and absent in all hypolactasia individuals. A second SNP (G-22 kbA) was concordant with phenotype in all but a few rare individuals. Since both SNPs are located in the same gene, this has led to a genetic means of testing lactase expression in individuals. Outside of the Finnish study, a separate study also confirmed that the CT SNP at -14kb is an indicator of lactase persistence, with the exception of two individuals.
Joel Hirschhorn of Harvard Medical School discovered that lactase persistence was due to the presence of a haplotype composed of more than 1 million nucleotide base pairs, including the lactase gene. The presence of this gene is the cause of lactase persistence. Today, this haplotype can be found in 80% of Europeans and Americans of European ancestry. On the other hand, the percentage of the population who are lactase persistent in sub-Saharan Africa and Southeast Asia is very low. It is absent in the Bantu of South Africa and most Chinese populations. These geographical distributions strongly correlate with the spread of domesticated cattle. About 5,000 to 10,000 years ago, this haplotype came under very strong selective pressure. This period matches the rise of dairy farming. As dairy farming originated in Europe, Europeans were exposed to increased lactose nutrition provided by dairy products, resulting in positive natural selection. The additional nutrition provided by the dairy was very important for survival in the recent history of Europe; therefore the supply of fresh milk leads to the favoring of the lactase persistent trait. As dairy farming spread across the globe, after the separation of Europe-derived populations from Asian- and African-derived populations, and after the colonization of Europe, the strong positive selection occurred in a large region, leading to the global spread of lactase persistence.
The question then arises: if lactase expression is not necessary after infancy, why has it persisted? Lactase expression persistence is largely due to natural selection. Natural selection is a component of evolution by which a trait affects the chances of the survival of organisms, and consequently, the trait becomes more prevalent in the population over time. Especially in Europe, the genetic variant -13,910*T has been strongly associated with lactase persistence and has been favored by natural selection in the past 10,000 years. Indeed, the consumption of lactose has been proven to benefit humans through adulthood. For example, the 2009 British Women's Heart and Health Study investigated the effects on women's health of the alleles that coded for lactase persistence. Where the C allele indicated lactase non-persistence and the T allele indicated lactase persistence, the study found that women that were homozygous for the C allele exhibited worse health than women with a C and a T allele and women with two T alleles. Women who were CC reported more hip and wrist fractures, more osteoporosis, and more cataracts than the other groups. They also were on average 4–6 mm shorter than the other women, as well as slightly lighter in weight. In addition, factors such as metabolic traits, socioeconomic status, lifestyle, and fertility were found to be unrelated to the findings, and thus it can be concluded that the lactase persistence benefited the health of these women.
Evidence that lactase persistence has been favored by natural selection was found in a 2006 study. The analysis process consisted of plotting extensive linkage disequilibrium of ancestral and current alleles. The researchers were able to conclude that the score did in fact reflect positive selection of lactase persistence. It has also been reported that lactase persistence presents stronger selection pressure than any other known human gene.
Lactase persistence in nonhumans
Lactose malabsorption is typical for adult mammals, and lactase persistence is a phenomenon likely linked to human interactions in the form of dairying. Most mammals lose the ability to digest lactose once they are old enough to find their own source of nourishment away from their mother. After weaning, or the transition from being breast-fed to consuming other types of food, their ability to produce lactase naturally diminishes as it is no longer needed. For example, in a study performed at Ohio State University, it was found that in the time a piglet aged from five to eighteen days, it lost 67% of its lactose absorption ability. While nearly all humans can normally digest lactose for the first 5 to 7 years of their life, most mammals stop producing lactase much earlier. Cows can be weaned from their mothers milk anywhere from 6 months to a year of age. Lambs are regularly weaned at an age of about 16 weeks. Such examples suggest that lactase persistence is a uniquely human phenomenon.
There is no reliable data available for Mongolians but it is estimated that their lactase persistence is very high because they are a nomadic nation and the Mongolian cuisine primarily consists of dairy products.
|Human group||Individuals examined||Intolerance (%)||Reference||Allele frequency|
|Europeans in Australia||160||4||||0.20|
|African American Children||N/A||45||||N/A|
|Saami (in Russia and Finland)||N/A||25–60||||N/A|
|North American Hispanics||N/A||53||||N/A|
|Mexican American Males||N/A||55||||N/A|
|Jews, Mizrahi (Iraq, Iran, etc.)||N/A||85||||N/A|
|Northeastern Han Chinese||248||92.3|||
The statistical significance of these figures vary greatly depending on number of people sampled.
Lactose intolerance levels also increase with age. At ages 2 – 3 yrs., 6 yrs., and 9 - 10 yrs., the amount of lactose intolerance is, respectively:
- 6% to 15% in white Americans and northern Europeans
- 18%, 30%, and 47% in Mexican Americans
- 25%, 45%, and 60% in black South Africans
- approximately 10%, 20%, and 25% in Chinese and Japanese
- 30–55%, 90%, and >90% in Mestizos of Peru
Chinese and Japanese populations typically lose between 20 and 30 percent of their ability to digest lactose within three to four years of weaning. Some studies have found that most Japanese can consume 200 ml (8 fl oz) of milk without severe symptoms (Swagerty et al., 2002).
Ashkenazi Jews can keep 20–30 percent of their ability to digest lactose for many years. Of the 10% of the Northern European population that develops lactose intolerance, the development of lactose intolerance is a gradual process spread out over as many as 20 years.
The ability to digest lactose into adulthood (lactase persistence) would have only been useful to humans after the invention of animal husbandry and the domestication of animal species that could provide a consistent source of milk. Hunter-gatherer populations before the Neolithic revolution were overwhelmingly lactose intolerant, as are modern hunter-gatherers. Genetic studies suggest that the oldest mutations associated with lactase persistence only reached appreciable levels in human populations in the last ten thousand years. Therefore lactase persistence is often cited as an example of both recent human evolution and, as lactase persistence is a genetic trait but animal husbandry a cultural trait, gene-culture coevolution in the mutual human-animal symbiosis initiated with the advent of agriculture.
Several genetic markers for lactase persistence have been identified, and these show that the allele has multiple origins in different parts of the world (i.e. it is an example of convergent evolution). The version of the allele most common amongst Europeans is estimated to have risen to significant frequencies about 7,500 years ago in the central Balkans and Central Europe, a place and time approximately corresponding to the archaeological Linearbandkeramik and Starčevo cultures. From there, it most probably spread eastwards as far as India. Likewise, one of the four alleles associated with lactase persistence in African population, is also probably of European origin. Since North Africans also possess this version of the allele it is probable that it actually originated earlier, in the Near East, but that the earliest farmers did not have high levels of lactase persistence and, subsequently, did not consume significant amounts of unprocessed milk. Lactase persistence in Sub-Saharan Africa almost certainly had a separate origin, probably more than one, and it is also likely that there was a separate origin associated with the domestication of the Arabian camel. None of the mutations so far identified have been shown to be causal for the lactase persistence allele, and it is thought that there are several more yet to be discovered.
The evolutionary processes driving the rapid spread of lactase persistence in some populations are not known. In some East African ethnic groups lactase persistence has gone from negligible to near-ubiquitous frequencies in just three thousand years, suggesting a very strong selective pressure. But some models for the spread of lactase persistence in Europe attribute it primarily to a form of genetic drift. Competing theories on why the ability to digest lactose might be selected for include nutritional benefits, milk as a water source in times of drought, and increased calcium absorption helping to prevent rickets and osteomalacia in low-light regions.
Roman authors recorded that the people of northern Europe, particularly Britain and Germany, drank unprocessed milk. This corresponds very closely with modern European distributions of lactose intolerance, where the people of Britain, Germany, and Scandinavia have a high tolerance, and those of southern Europe, especially Italy, have a lower tolerance.
In east Asia, historical sources also attest that the Chinese did not consume milk, whereas the nomads who lived on the borders did. Again, this reflects modern distributions of intolerance. China is particularly notable as a place of poor tolerance, whereas in Mongolia and the Asian steppes mare milk is drunk regularly. This tolerance is thought to be advantageous, as the nomads do not settle down long enough to process mature cheese. Given that their prime source of income is generated through horses, to ignore their milk as a source of nourishment would be foolish. The nomads also make an alcoholic beverage, called kumis, from mare milk, although the fermentation process reduces the amount of lactose present.
- Swallow, D. M. (2003). "Genetics of lactase persistence and lactose intolerance". Annual Review of Genetics 37: 197–219. doi:10.1146/annurev.genet.37.110801.143820. PMID 14616060.
- Bersaglieri, T.; Sabeti, P. C.; Patterson, N.; Vanderploeg, T.; Schaffner, S. F.; Drake, J. A.; Rhodes, M.; Reich, D. E.; Hirschhorn, J. N. (2004). "Genetic Signatures of Strong Recent Positive Selection at the Lactase Gene". The American Journal of Human Genetics 74 (6): 1111–1120. doi:10.1086/421051. PMC 1182075. PMID 15114531.
- Troelsen JT (May 2005). "Adult-type hypolactasia and regulation of lactase expression". Biochim. Biophys. Acta 1723 (1–3): 19–32. doi:10.1016/j.bbagen.2005.02.003. PMID 15777735.
- Wang Y, Harvey CB, Hollox EJ, Phillips AD, Poulter M, Clay P, Walker-Smith JA, Swallow DM (June 1998). "The genetically programmed down-regulation of lactase in children". Gastroenterology 114 (6): 1230–6. doi:10.1016/S0016-5085(98)70429-9. PMID 9609760.
- Harvey CB, Wang Y, Hughes LA, Swallow DM, Thurrell WP, Sams VR, Barton R, Lanzon-Miller S, Sarner M (January 1995). "Studies on the expression of intestinal lactase in different individuals". Gut 36 (1): 28–33. doi:10.1136/gut.36.1.28. PMC 1382348. PMID 7890232.
- Lloyd M, Mevissen G, Fischer M, Olsen W, Goodspeed D, Genini M, Boll W, Semenza G, Mantei N (February 1992). "Regulation of intestinal lactase in adult hypolactasia". J. Clin. Invest. 89 (2): 524–9. doi:10.1172/JCI115616. PMC 442883. PMID 1737843.
- Troelsen JT, Olsen J, Møller J, Sjöström H (December 2003). "An upstream polymorphism associated with lactase persistence has increased enhancer activity". Gastroenterology 125 (6): 1686–94. doi:10.1053/j.gastro.2003.09.031. PMID 14724821.
- Bersaglieri T et al.; Sabeti, Pardis C.; Patterson, Nick; Vanderploeg, Trisha; Schaffner, Steve F.; Drake, Jared A.; Rhodes, Matthew; Reich, David E.; Hirschhorn, Joel N. (June 2004). "Genetic Signatures of Strong Recent Positive Selection at the Lactase Gene". Am J Hum Genet 74 (6): 1111–20. doi:10.1086/421051. PMC 1182075. PMID 15114531.
- Hussin J, Nadeau P, Lefebvre JF, Labuda D (2010). "Haplotype allelic classes for detecting ongoing positive selection". BMC Bioinformatics 11: 65. doi:10.1186/1471-2105-11-65. PMC 2831848. PMID 20109229.
- Itan Y, Powell A, Beaumont MA, Burger J, Thomas MG (August 2009). "The origins of lactase persistence in Europe". In Tanaka, Mark M. PLoS Comput. Biol. 5 (8): e1000491. doi:10.1371/journal.pcbi.1000491. PMC 2722739. PMID 19714206.
- Bersaglieri T, Sabeti PC, Patterson N, Vanderploeg T, Schaffner SF, Drake JA, Rhodes M, Reich DE, Hirschhorn JN (June 2004). "Genetic signatures of strong recent positive selection at the lactase gene". Am. J. Hum. Genet. 74 (6): 1111–20. doi:10.1086/421051. PMC 1182075. PMID 15114531.
- Rabot S, Rafter J, Rijkers GT, Watzl B, Antoine JM (March 2010). "Guidance for substantiating the evidence for beneficial effects of probiotics: impact of probiotics on digestive system metabolism". J. Nutr. 140 (3): 677S–89S. doi:10.3945/jn.109.113738. PMID 20107147.
- Smith GD, Lawlor DA, Timpson NJ, Baban J, Kiessling M, Day IN, Ebrahim S (March 2009). "Lactase persistence-related genetic variant: population substructure and health outcomes". Eur. J. Hum. Genet. 17 (3): 357–67. doi:10.1038/ejhg.2008.156. PMC 2986166. PMID 18797476.
- 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 (January 2007). "Convergent adaptation of human lactase persistence in Africa and Europe". Nat. Genet. 39 (1): 31–40. doi:10.1038/ng1946. PMC 2672153. PMID 17159977.
- Kretchmer N (October 1989). "Expression of lactase during development". Am. J. Hum. Genet. 45 (4): 487–8. PMC 1683494. PMID 2518796.
- Murray RD, Ailabouni AH, Powers PA, McClung HJ, Li BU, Heitlinger LA, Sloan HR (July 1991). "Absorption of lactose from colon of newborn piglet". Am. J. Physiol. 261 (1 Pt 1): G1–8. PMID 1907103.
- Menéndez-Buxadera A, Carleos C, Baro JA, Villa A, Cañón J (February 2008). "Multi-trait and random regression approaches for addressing the wide range of weaning ages in Asturiana de los Valles beef cattle for genetic parameter estimation". J. Anim. Sci. 86 (2): 278–86. doi:10.2527/jas.2007-0252. PMID 17998432.
- Bickell S, Poindron P, Nowak R, Chadwick A, Ferguson D, Blache D (November 2009). "Genotype rather than non-genetic behavioural transmission determines the temperament of Merino lambs". Animal Welfare 18 (4): 459–466.
- for the C (lactase non-persistence) allele
N.2FAwas invoked but never defined (see the help page).
Cite error: The named reference
- Flatz G (1987). "Genetics of lactose digestion in humans". Adv. Hum. Genet. 16: 1–77. PMID 3105269.
- Timo Sahi (N/A). "Genetics and epidemiology of adult-type hypolactasia with emphasis on the situation in Europe". Scandinavian Journal of Nutrition/Naringsforskning.
- Kretchmer N (1972). "Lactose and lactase". Sci. Am. 227 (4): 71–8. PMID 4672311.
- Almon, R; Engfeldt, P; Tysk, C; Sjöström, M; Nilsson, TK (2007). "Prevalence and trends in adult-type hypolactasia in different age cohorts in Central Sweden diagnosed by genotyping for the adult-type hypolactasia-linked LCT -13910C > T mutation". Scandinavian journal of gastroenterology 42 (2): 165–70. doi:10.1080/00365520600825257. PMID 17327935.
- Torniainen, S.; Hedelin, M.; Autio, V.; Rasinpera, H.; Balter, K. A.; Klint, A.; Bellocco, R.; Wiklund, F. et al. (2007). "Lactase Persistence, Dietary Intake of Milk, and the Risk for Prostate Cancer in Sweden and Finland". Cancer Epidemiology Biomarkers & Prevention 16 (5): 956–61. doi:10.1158/1055-9965.EPI-06-0985. PMID 17507622.
- Enattah, N; Trudeau, A; Pimenoff, V; Maiuri, L; Auricchio, S; Greco, L; Rossi, M; Lentze, M et al. (2007). "Evidence of Still-Ongoing Convergence Evolution of the Lactase Persistence T-13910 Alleles in Humans". The American Journal of Human Genetics 81 (3): 615–25. doi:10.1086/520705. PMC 1950831. PMID 17701907.
- de Vrese M, Stegelmann A, Richter B, Fenselau S, Laue C, Schrezenmeir J (2001). "Probiotics--compensation for lactase insufficiency". Am. J. Clin. Nutr. 73 (2 Suppl): 421S–429S. PMID 11157352.
- Smith et al, G.D.; Lawlor, Debbie A; Timpson, Nic J; Baban, Jamil; Kiessling, Matt; Day, Ian N M; Ebrahim, Shah (2008). "Lactase persistence-related genetic variant: population substructure and health outcomes". European Journal of Human Genetics 17 (3): 357. doi:10.1038/ejhg.2008.156. PMC 2986166. PMID 18797476.
- Flatz, G.; Howell, J.N.; Doench, J.; Flatz, S.D. (1982). "Distribution of physiological adult lactase phenotypes, lactose absorber and malabsorber, in Germany". Human Genetics 62 (2): 152–7. doi:10.1007/BF00282305. PMID 6819221.
- Heli Rasinperä (April 2006). "ADULT-TYPE HYPOLACTASIA: Genotype-phenotype correlation".
- Prevalence of the lactase deficiency among the population of the northwestern region of Russia
- Cavalli-Sforza LT, Strata A, Barone A, Cucurachi L (1987). "Primary adult lactose malabsorption in Italy: regional differences in prevalence and relationship to lactose intolerance and milk consumption" (PDF). Am. J. Clin. Nutr. 45 (4): 748–54. PMID 3565303.
- Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Järvelä I (2002). "Identification of a variant associated with adult-type hypolactasia". Nat. Genet. 30 (2): 233–7. doi:10.1038/ng826. PMID 11788828.
- "Lactose Intolerance: The Molecular Explanation". UC Davis Nutritional Genomics.
- (Portuguese) Intolerância à lactose Maria do Céu Salgado - Outubro de 2007
- Kozlov A, Lisitsyn D (1997). "Hypolactasia in Saami subpopulations of Russia and Finland". Anthropol Anz 55 (3–4): 281–7. PMID 9468755.
- Jackson RT, Latham MC (1979). "Lactose malabsorption among Masai children of East Africa". Am. J. Clin. Nutr. 32 (4): 779–82. PMID 581925.
- Ernest L. Abel (August 2001). Jewish Genetic Diseases: a Layman's Guide. McFarland & Company, Inc., Publishers. ISBN 978-0-7864-0941-9.
- Burgio GR, Flatz G, Barbera C, et al. (1984). "Prevalence of primary adult lactose malabsorption and awareness of milk intolerance in Italy" (PDF). Am. J. Clin. Nutr. 39 (1): 100–4. PMID 6691285.
- Vesa TH, Marteau P, Korpela R (2000). "Lactose intolerance". J Am Coll Nutr 19 (2 Suppl): 165S–175S. PMID 10759141.
- Nasrallah SM (1979). "Lactose intolerance in the Lebanese population and in "Mediterranean lymphoma"" (PDF). Am. J. Clin. Nutr. 32 (10): 1994–6. PMID 484518.
- Wang YG, Yan YS, Xu JJ, et al. (1984). "Prevalence of primary adult lactose malabsorption in three populations of northern China". Hum. Genet. 67 (1): 103–6. doi:10.1007/BF00270566. PMID 6235167.
- Sahi T (1994). "Genetics and epidemiology of adult-type hypolactasia". Scand. J. Gastroenterol. Suppl. 202: 7–20. doi:10.3109/00365529409091740. PMID 8042019.
- Woteki CE, Weser E, Young EA (1976). "Lactose malabsorption in Mexican-American children" (PDF). Am. J. Clin. Nutr. 29 (1): 19–24. PMID 946157.
- Yoshida Y, Sasaki G, Goto S, Yanagiya S, Takashina K (1975). "Studies on the etiology of milk intolerance in Japanese adults". Gastroenterol. Jpn. 10 (1): 29–34. PMID 1234085.
- Matthews SB, Waud JP, Roberts AG, Campbell AK (2005). "Systemic lactose intolerance: a new perspective on an old problem". Postgrad Med J 81 (953): 167–73. doi:10.1136/pgmj.2004.025551. PMC 1743216. PMID 15749792.
- Swaminathan, N. 2007. Not Milk? Neolithic Europeans Couldn't Stomach the Stuff. Scientific American.
- Malmstrom H., Linderholm A., Liden K., Stora J., Molnar P., Holmlund G., Jakkobson M., Gotherstrom A. (2010). "High frequency of lactose intolerance in a prehistoric hunter-gatherer population in northern Europe". BMC Evolutionary Biology 10: 89.
- Coelho M., Luiselli D., Bertorelle G., Lopes A. I., Seixas S., Destro-Bisol G., Rocha J. (2002). "Microsatellite variation and evolution of human lactase persistence". Human Genetics 117 (4): 329–339. doi:10.1007/s00439-005-1322-z. PMID 15928901.
- Bersaglieri T., Sabeti P. C., Patterson N., Vanderploeg T., Schaffner S. F., Drake J. A., Rhodes M., Reich D. E., Hirschhorn J. N. et al. (2004). "Genetic signatures of strong recent positive selection at the lactase gene". American Journal of Human Genetics 74 (6): 1111–20. doi:10.1086/421051. PMC 1182075. PMID 15114531.
- Wade, N. Study Detects Recent Instance of Human Evolution. The New York Times. December 10, 2006.
- Swaminathan, N. 2006. African Adaptation to Digesting Milk Is "Strongest Signal of Selection Ever". Scientific American.
- Aoki K (2001). "Theoretical and Empirical Aspects of Gene–Culture Coevolution". Theoretical Population Biology 59 (4): 253–261. doi:10.1006/tpbi.2001.1518. PMID 11560446.
- Swallow D. M. (2003). "Genetics of Lactase Persistence and Lactose Intolerance". Annual Review of Genetics 37: 197–219. doi:10.1146/annurev.genet.37.110801.143820. PMID 14616060.
- Itan Y, Powell A, Beaumont MA, Burger J, Thomas MG (2009). "The Origins of Lactase Persistence in Europe". PLoS Comput Biol 5 (8): e1000491. doi:10.1371/journal.pcbi.1000491. PMC 2722739. PMID 19714206.
- Myles S., Bouzekri N., Haverfield E., Cherkaoui M., Dugoujon J. M., Ward R. (2005). "Genetic evidence in support of a shared Eurasian-North African dairying origin". Biomedical and Life Sciences 117 (1): 34–42.
- Tishkoff S. A.; Reed, Floyd A; Ranciaro, Alessia; Voight, Benjamin F; Babbitt, Courtney C; Silverman, Jesse S; Powell, Kweli; Mortensen, Holly M; Hirbo, Jibril B; Osman, Maha; Ibrahim, Muntaser; Omar, Sabah A; Lema, Godfrey; Nyambo, Thomas B; Ghori, Jilur; Bumpstead, Suzannah; Pritchard, Jonathan K; Wray, Gregory A; Deloukas, Panos (2006). "Convergent adaptation of human lactase persistence in Africa and Europe". Nature Genetics 39: 31–40. doi:10.1038/ng1946. PMC 2672153. PMID 17159977.
- Enattah N. S., Jensen T. G. K., Nielsen M., Lewinski R., Kuokkanen M., Rasinpera H., El-Shanti H., Kee Seo J., Alifrangis M. et al. (2008). "Independent Introduction of Two Lactase-Persistence Alleles into Human Populations Reflects Different History of Adaptation to Milk Culture". American Journal of Human Genetics 82 (1): 57–72. doi:10.1016/j.ajhg.2007.09.012. PMC 2253962. PMID 18179885.
- Itan Y., Jones B. L., Ingram C. J. E., Swallow D. M., Thomas M. G. (2010). "A worldwide correlation of lactase persistence phenotype and genotypes". BMC Evolutionary Biology 10: 36. doi:10.1186/1471-2148-10-36.
- Itan, Y., Powell, A., Beaumont, M. A., Burger, J., Thomas, M. G. 2009. The Origins of Lactase Persistence in Europe. PLoS Computational Biology 5(8): e1000491.
- "Lactose tolerance/intolerance". Gene Expression. January 19, 2004. Retrieved 2008-01-31.