By Thomas Yuang Li, IV Form
The Evolution of Lactose Tolerance
Some people are lactose tolerant because they are lactase persistent (LP). Lactase is an enzyme responsible for the hydrolysis reaction or breakdown of lactose, the sugar in milk, and it helps human digest milk. LP is the continued activity of lactase in human adulthood. LP occurs because of the inheritance of genetic mutations that result in LP. It became prevalent in some societies due to evolution through natural selection. As of 2018, around 65% of the world population experienced lactose intolerance (NIH). The distribution gradient is uneven, for about 90% of the population in East Asia are lactose intolerant while about only 10% of the population in North Western Europe are lactose intolerant.
Lactose is a disaccharide that contains a galactose and a glucose unit. Lactose makes up 6-8% of milk. Humans can only digest lactose with the help of lactase, making lactase critical in the digestion of milk. Lactase is produced by small intestine cells. It accelerates the hydrolysis reaction or breakdown of lactose. Through hydrolysis, lactose is broken down into glucose and galactose, which are monosaccharides, or simple sugar molecules, that can be absorbed into the human bloodstream. Lactase catalyzes this hydrolysis reaction by lowering the activation energy, the minimum energy required to initiate a chemical reaction. Without sufficient lactase, humans cannot fully digest lactose. As shown in Figure 1, the undigested lactose then passes on to the large intestine, where it interacts with bacteria and ferments. The fermentation causes symptoms of lactose intolerance, which range from bloating to diarrhea.
Humans are originally genetically programmed to reduce or terminate lactase production after the weaning period. Since humans originally ceased drinking milk after the weaning period, they no longer needed lactase. The termination of lactase production thus saves humans energy and resources. However, with the advent of pastoral societies, milk became a food source for human adults. Thus, LP became a favorable trait in pastoral societies.
LP is a phenotype, an observable trait, resulting from genetic mutations in DNA. More specifically, several single nucleotide polymorphisms (SNP), the variation in a single base pair in the DNA sequence, are found to be related to LP. As shown in Figure 2, the related SNPs are located in the MCM6 gene, which is upstream from LCT, the gene that encodes lactase. The SNPs in MCM6 intron 9 and 13 differentially leads to the activation of lactase production. Different, formerly unconnected populations in the world are found to have evolved LP independently in different time periods, making the evolution of LP a convergent evolution. The LP phenotype developed in different populations also results from different SNPs. Shown in Figure 2, the European LP population have base variations in nucleotides that are different from the African LP population. Additionally, the LP alleles are found to be dominant, meaning it can be expressed in heterozygous individuals. Heterozygous individuals have one LP allele and one non-LP allele. By being a dominant trait, the LP phenotypic frequency increases faster in populations than if it were a recessive trait. In such cases, it would be unable to be expressed in heterozygous individuals where a dominant trait would overshadow the recessive trait.
People from certain parts of the world are more likely to have LP. Currently, LP trait frequency is found in about 35% of the adult population in the world. However, the demographic distribution of LP is uneven. As shown in Figure 3, LP is most commonly distributed in Northern Europe and Western Africa, where about 90% of the population exhibits lactase persistence. In South-Eastern Asia, however, less than 10% of the population is LP. The uneven distribution of LP is due to the historical cultural differences in populations. Northern Europe and Western Africa were both pastoral societies where there has been a long history (more than 8000 years) of dairy consumption. In contrast, in South-Eastern Asia, milk was adopted as a food source much later, not until 1500 years ago. The difference in time length of dairy consumption leads to the difference in LP distribution because of the process of evolution.
The evolution of LP started with a random genetic mutation in an individual living in a pastoral society, which lead the individual to be LP. Therefore a variation in phenotype was added into a population. Because LP is an inheritable and dominant trait, the individual could pass on the gene for LP on to his offspring. Furthermore, in the worst case when the LP parent is heterozygous and the other parent did not have the mutation, LP still has a 50% chance of being expressed in their offspring, as shown in Figure 4. The rapid increase of LP alleles frequency can be explained through a theory based on selective pressure, which one or multiple famines occurred. In times without famines, people have multiple food sources available to them, so there is not much contrast between the survival rate of individuals without LP and individuals with LP. Thus, LP allele frequency in a population would likely not increase rapidly . However, during a famine, available food sources decrease. Since people with LP have milk as an additional food source, their survival rate is higher than those without LP. As shown in figure 5, after the famine, more LP individuals lived than non-LP individuals, thus increasing the LP alleles frequence in the certain population. The LP frequency continues to grow as the LP individuals marries non-LP individuals and they produce offspring since LP, being a dominant trait, would be more likely to be expressed. If the individual does not live in a pastoral society, the LP evolution is not likely to occur. This is because LP individuals have no advantage in competitive environments. Thus, LP does not improve the individual’s fitness, ability to survive and reproduce fertile offspring, in a non-pastoral society. As a result, the allele frequency of LP will not increase, and the individuals with the mutated gene are likely to die out.
Some people are lactose tolerant because they inherited the mutated gene that makes them lactase persistent. People from certain regions in the world are more likely to inherit the LP gene because the LP allele frequency in their population is higher, likely due to historical food source differences. Currently, the lactose intolerant population is about 20% in North America, resembling that in Europe, which is reasonable given that most of the population in North America was migrated from Europe. The lactose intolerant population is about 60% in South America, about 15% higher than that of the Iberian Peninsula. Such discrepancy is likely a result of the high percentage interaction between between the initially different population groups, such as populations from the Iberian Peninsula, Africa, and among indigenous peoples.
Thomas Yuang Li is a IV form boarding student from San Francisco Bay Area, CA. He loves science.
Gerbault, Pascale et al. “Evolution of lactase persistence: an example of human niche construction.” Philosophical transactions of the Royal Society of London. Series B, Biological sciences vol. 366,1566 (2011): 863-77. doi:10.1098/rstb.2010.0268
Strode, Paul. Got Lactase? The Co-Evolution of Genes and Culture: In-Depth Film Guide. Howard Hughes Medical Institute, 3 Mar. 2011. Bio Interactive,
http://www.biointeractive.org/sites/default/files/IDG_Lactase.pdf. Accessed 18 Nov. 2019.