It'd be impossible to discuss nutrition and genetics without discussion human milk consumption and lactose (in)tolerance. This example is iconic in that it has huge evolutionary and nutrition implications.
From an evolutionary perspective, lactase persistence's relatively widespread distribution is largely due to the success of the agricultural revolution. Milk provides an excellent source of calories, nutrients, animal based amino acids and, often not considered, hydration to any species that can consume it. For most humans, and mammals in general, milk is food for infants. Following weaning, there is low digestive capacity of lactose, and for humans, milk consumed in a non-fermented form in excess of 500mL can be quite uncomfortable. There is potentially good evolutionary reason for this loss of lactase persistence: lactase is able to digest some glycosides found in plants, such as berries and nightshade plants, that would allow for the release of cyanides and other toxic substances. However, not all glycosides are dangerous and this shouldn't deter you from eating foods containing these substances.
Lactose is a disaccharide consisting of a molecule of glucose and a molecule of galactose, joined by a beta 1-4 linkage. Lactase, encoded by the LCT gene, is a brush border enzyme found in the proximal small intestine that is able to hydrolyze lactose into its two monosaccharide constituents. The LCT gene contains 17 exons and 2 enhancer elements 14,000-22,000 base pairs upstream from the sequence.
To understand why about 75% of the world can't digest lactose, we must look at 2 mutations that occur in these enhancer elements.
The -13910T variant keeps the enhancing region active, as is found in most individuals of Northern European descent, maintaining mucosal brush border villi expression of lactase throughout the adult life. A second region, known as the -22018A variant also enhances lactase expression. Having either one or both of these alleles confers high digestive capacity of lactose and is known as having the LAC P gene (P for persistance) - LAC P is dominant. The LAC R gene, conferring low digestive capacity of lactose, is recessive and only exhibited in homozygous individuals. A study in 2006 by Sarah Tishkoff's lab at the University of Pennsylvania confirmed that there is significant linkage disequilibrium between ancestral and modern current allele frequencies, indicating that lactase persistance did undergo positive selection. It's very easy to look back and create a nice story about raising cow's, drinking milk and lactase persistence, but it is essential to look back at ancestral allele frequencies and compare them to modern allele frequencies. Selection is not the only force of evolution - if these alleles conferring lactase persistance had been in existence, drifting in the ancestral populations, devoid of dairy products to act as a selective force, the ancestral alleles could have been in the same 3:1 ratio that it is currently in. It is easy to dismiss this possibility in retrospect with the picture being as clear as it is now but before we knew allele frequencies in specific populations and had adequate archaeological data on farming, selection would not have been a scientific assumption. This caveat is important for identifying future alleles and attributing their prevalance to be due to selection.
From a clinical perspective, it is important to note that diagnosing lactose intolerance should be done by genotyping, Lactose Hydrogen Breath Test, or Jejunum Biopsy. Self reporting of lactose intolerance, published in the New England Journal of Medicine by Suarez et al, showed that there is no significant differences in symptoms reported by lactose intolerant individuals who were blindly double blind randomized to 8oz of milk with 12g of lactose or 12g of hydrolyzed lactose - aka, individuals are notoriously bad at diagnosing themselves. Also, of note, is that symptoms of lactose intolerance and IBS also overlap in many places - abdominal pain, intestinal bloating, flatulence, loose stools, etc. As milk is an important source of nutrients, especially calcium, for individuals, self diagnosis of lactose intolerance should be avoided if possible (not that there aren't non-dairy sources of calcium, some even better like dark leafy low-oxalate greens).
While not directly related to lactase persistence, a rare defect in the SGLT1 gene, a sodium-glucose transporter, leads to a malabsorption of glucose and galactose. This can cause severe and potentially fatal diarrhea if fed milk - this is especially concerning for breastfeeding infants.
References:
Lucock, M. Molecular Nutrition and Genomics. 2007. Wiley Press
Kaput, J. et al. Nutritional Genomics. 2006. Wiley Press
Kohlmeier, M. Nutrigenetics: Apply the Science of Personal Nutrition, 2013. Academic Press
From an evolutionary perspective, lactase persistence's relatively widespread distribution is largely due to the success of the agricultural revolution. Milk provides an excellent source of calories, nutrients, animal based amino acids and, often not considered, hydration to any species that can consume it. For most humans, and mammals in general, milk is food for infants. Following weaning, there is low digestive capacity of lactose, and for humans, milk consumed in a non-fermented form in excess of 500mL can be quite uncomfortable. There is potentially good evolutionary reason for this loss of lactase persistence: lactase is able to digest some glycosides found in plants, such as berries and nightshade plants, that would allow for the release of cyanides and other toxic substances. However, not all glycosides are dangerous and this shouldn't deter you from eating foods containing these substances.
Lactose is a disaccharide consisting of a molecule of glucose and a molecule of galactose, joined by a beta 1-4 linkage. Lactase, encoded by the LCT gene, is a brush border enzyme found in the proximal small intestine that is able to hydrolyze lactose into its two monosaccharide constituents. The LCT gene contains 17 exons and 2 enhancer elements 14,000-22,000 base pairs upstream from the sequence.
To understand why about 75% of the world can't digest lactose, we must look at 2 mutations that occur in these enhancer elements.
The -13910T variant keeps the enhancing region active, as is found in most individuals of Northern European descent, maintaining mucosal brush border villi expression of lactase throughout the adult life. A second region, known as the -22018A variant also enhances lactase expression. Having either one or both of these alleles confers high digestive capacity of lactose and is known as having the LAC P gene (P for persistance) - LAC P is dominant. The LAC R gene, conferring low digestive capacity of lactose, is recessive and only exhibited in homozygous individuals. A study in 2006 by Sarah Tishkoff's lab at the University of Pennsylvania confirmed that there is significant linkage disequilibrium between ancestral and modern current allele frequencies, indicating that lactase persistance did undergo positive selection. It's very easy to look back and create a nice story about raising cow's, drinking milk and lactase persistence, but it is essential to look back at ancestral allele frequencies and compare them to modern allele frequencies. Selection is not the only force of evolution - if these alleles conferring lactase persistance had been in existence, drifting in the ancestral populations, devoid of dairy products to act as a selective force, the ancestral alleles could have been in the same 3:1 ratio that it is currently in. It is easy to dismiss this possibility in retrospect with the picture being as clear as it is now but before we knew allele frequencies in specific populations and had adequate archaeological data on farming, selection would not have been a scientific assumption. This caveat is important for identifying future alleles and attributing their prevalance to be due to selection.
From a clinical perspective, it is important to note that diagnosing lactose intolerance should be done by genotyping, Lactose Hydrogen Breath Test, or Jejunum Biopsy. Self reporting of lactose intolerance, published in the New England Journal of Medicine by Suarez et al, showed that there is no significant differences in symptoms reported by lactose intolerant individuals who were blindly double blind randomized to 8oz of milk with 12g of lactose or 12g of hydrolyzed lactose - aka, individuals are notoriously bad at diagnosing themselves. Also, of note, is that symptoms of lactose intolerance and IBS also overlap in many places - abdominal pain, intestinal bloating, flatulence, loose stools, etc. As milk is an important source of nutrients, especially calcium, for individuals, self diagnosis of lactose intolerance should be avoided if possible (not that there aren't non-dairy sources of calcium, some even better like dark leafy low-oxalate greens).
While not directly related to lactase persistence, a rare defect in the SGLT1 gene, a sodium-glucose transporter, leads to a malabsorption of glucose and galactose. This can cause severe and potentially fatal diarrhea if fed milk - this is especially concerning for breastfeeding infants.
References:
Lucock, M. Molecular Nutrition and Genomics. 2007. Wiley Press
Kaput, J. et al. Nutritional Genomics. 2006. Wiley Press
Kohlmeier, M. Nutrigenetics: Apply the Science of Personal Nutrition, 2013. Academic Press
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