Lactase persistence, you might be a mutant!

Written by: MARIYAM MALSA ANEES, CLASS OF 2023

Lactase is an enzyme that is found on the brush border of the small intestine in humans and various other mammals. This enzyme is crucial for the breakdown of Lactose, a major constituent of mammalian milk, into glucose and galactose.

The activity of lactase can be detected very early on in the development of the embryo and it peaks upon birth. However, for the majority of the human population the expression of lactase diminishes very early on in life. This downward sequence begins at 2-3 years of age and generally reaches cessation by 5-10 years of age. Thus, most adolescents have very minimal quantities of lactase and are unable to digest lactose and are said to have the trait of lactose non-persistence otherwise referred to as lactose intolerance

If you take a look at the different types of lactase intolerance it can be either primary, secondary or congenital lactose intolerance. Primary lactose intolerance is the most common type, in which the people are able to digest lactose as children but lose the ability to do so once they reach adolescence i.e. the lactase expression gene turns off.

Secondary lactose intolerance is where a disease affecting the small intestine (inflammatory conditions, viral infections) can result in temporary lactase deficiency in individuals that are normally lactose tolerant. In this case the condition is reversible with treatment of underlying condition. Finally, Congenital Lactose Intolerance is a very rare disorder in which lactase is deficient from birth.

However, in certain human populations the activity of lactase remains constant throughout their life. This is called lactase persistence. Then the question arises why is it such? This is a very classical example of natural selection among humans. However, the reason as to why the ability to digest Lactose remains the superior gene is open to speculation.

The main hypothesis which explains the reason for the positive selection of the lactase persistence gene is the GeneCulture Coevolution Hypothesis. It is based on the observation that pastoralist populations presented with high frequency of lactase persistence.

For Individuals who are lactase persistent, ability to digest lactose would prove to be more nutritionally advantageous as milk would have been a faster means of nutrition rather than raising animals and then slaughtering them and repeating the cycle. This would have been especially advantageous during periods famines and starvation as it would have provided for an alternative means of nutrition.

Two scenarios have been proposed for the Gene-Culture Coevolution Hypothesis. That is Culture-Historical Hypothesis and ReverseCause Hypothesis. According to CultureHistorical Hypothesis, the main reason for lactase persistence would be the introduction of dairy farming meaning lactase persistence developed and was selected positively with the onset of pastoralism. For Reverse-Cause Hypothesis, it argues that pastoralism was embraced within societies that already had high frequency of lactase persistence.

Contrary to this for populations independent of pastoralism, no selective advantage was present and hence, any mutations present within these populations would have been simply neutral mutations.

Thus, if you look at the frequency of lactase persistence (from image below) you can see a distribution pattern of this trait been predominantly seen in individuals with northern European ancestry, especially Scandinavian, and in certain other populations, including some of the nomadic peoples of the middle east and Africa. Lactose non-persistence is observed in a majority of the world's populations, including most of those with Asian or African forebearers.

Why are lactase persistent people referred to as the mutants?

This is because our forefathers were extremely lactose intolerant. This theory was proved by the sequencing of DNA from skeletal remains of eight neolithic individuals who lived across Europe between 5800 and 5000 years BC, which revealed that they all were homozygous for the lactase non-persistence allele. Furthermore, other genetic studies conducted indicate that the oldest mutations associated with lactase persistence only reached substantial levels in the last 10,000 years.

Not only that, via various extensive studies, so called Gain of Function mutation have been identified in people with Lactase Persistence. Gain of Function Mutation means that through small changes in the DNA sequence there is new unique beneficial characteristics. In this case the ability to digest Lactose.

Are there any benefits of lactase persistence?

The 2009 British Women's Heart and Health Study researched the effects of the alleles on women's health that coded for lactase persistence. In the study C allele indicated lactase non-persistence and the T allele indicated lactase persistence. It was found that women who were homozygous for the C allele presented worse health, than women with a C and a T allele, and women with two T alleles. Not only that, women who were CC reported more hip and wrist fractures, more osteoporosis,and more cataracts than others. Moreover, they also were on average 4–6 mm shorter as well as slightly lighter in weight. In addition, influences such as metabolic traits, socioeconomic status, lifestyle, and fertility were found to be isolated to the findings. Hence, from this study it proved that lactase persistence benefited the health of these women.

Also, since Lactose favors the intestinal absorption of calcium, it is advantageous in regions of low sunlight exposure where Vitamin D, necessary for the transport of calcium, is a restrictive factor and thereby prevent conditions such as rickets and osteomalacia.

A hypothesis for arid climates proposed suggested using milk to be advantageous during epidemics such as cholera where water is contaminated. In these situations, milk can become a source of hydration.