BioTechniques
07/08/2016 Sanjay Mishra
Human ancestors were largely vegetarian, thus evolving genes that help us thrive on plants. What does this mean for current day omnivores? Find out...
Like chimpanzees, our nearest evolutionary relatives, early hominins were mostly vegetarian. As we evolved, we experimented and adapted to a smörgåsbord of choices. A variety of food sources ensures that we get ample nutrients, especially the essential ones our bodies cannot make, such as Omega 6 and Omega 3 fats. Now, in a study published in the journal Molecular Biology and Evolution, scientists show that evolution adapted us to best use the kinds of fats we get from our diets, but these adaptations can have consequences with changing dietary patterns.
In the body, Fatty Acid Desaturases (FADS) help convert Omega 6 and Omega 3 fats from plant oils or fish and meat to physiologically important long-chain polyunsaturated fatty acids (LCPUFA). Frequent mutations in these genes cause several abnormalities, suggesting that FADS genes are fast evolving. Tom Brenna and Kumar Kothapalli from Cornell University were interested in looking for evolutionary hot spots in FADS, which can be used to trace the origin of the genes and populations.
The team first combed through the International HapMap, a global collection of human DNA sequence variations. In 2012, they discovered a genetic variant resulting in a 22 base pair (bp) insertion / deletion that impaired FADS2, meaning that carriers of the deletion increasingly rely on their diets for LCPUFA.
Conversely, exclusive plant eaters must accommodate for the lack of meat as a source for LCPUFA. “We had the hypothesis that the insertion allele might metabolize the LCPUFA precursors more efficiently than the deletion allele and that vegetarians might have fast metabolizing capacity,” Kothapalli said.
Could the ability to convert plant oils to LCPUFA have evolutionary implications? To find out, Brenna’s collaborators gathered blood samples from vegetarian donors in Pune, India, and omnivorous donors in Kansas, USA and looked for the insertion and deletion in FADS2 using PCR and DNA sequencing.
They found that almost all vegetarians carried the insertion allele, but the deletion was extremely rare. Compared to the omnivore population, almost four times as many vegetarians carried two copies of the insertion allele (I/I). In contrast, about half of the tested US population carried both copies of the deletion allele (D/D).
“It was too good to be true!” Brenna said. “We thought we made a mistake, so we repeated the experiments.” But their results on the evolutionary selection of FADS corresponded perfectly with another study in a Greenlandic Inuit population, which show similar FADS gene selection to accommodate a diet consisting mainly of fish.
Excited by their results from populations with contrasting diets, the scientists then looked for a worldwide pattern by exploring data from the 1000 Genomes Project. They found that the I/I genotype is highest in African and South Asian populations, but lower in European and East Asian populations.
The dramatic difference in the frequency of this FADS2 variant among the ethnic groups prompted Alon Keinan in Brenna’s team to wonder whether the insertion or deletion happened earlier in human evolution. By analyzing related sequences, his team calculated that the insertion allele is ancestral. In fact, both Neanderthals and Denisovans carried this allele.
But does this alter the ability of individuals to make LCPUFA from their diets? Over the next several months, the researchers analyzed the fats carried in volunteers' blood and found that the insertion carriers were better at converting plant oils into omega-6 LCPUFA. While everyone consumed the same amount of plant oil (LA), the insertion carriers accumulated far higher blood levels of the omega-6 arachidonic acid (ARA), which is proinflammatory. Unfortunately, they also made much less anti-inflammatory omega-3 acids – EPA and DHA because their conversion machinery was overwhelmed with producing ARA. This imbalance in omega-6 and omega-3 LCPUFA can have serious health implications. “Of course, Omega-6 is an essential nutrient, but it’s too much of a good thing. That we need to worry about,” Brenna cautioned.
David Katz, Director of the Yale-Griffin Prevention Research Center, who was not involved in this study said the results showcase that, “adaptations that are good in a native context may become a major liability.” These study results imply that for those with a long history of a cultural vegetarian diet, adopting an industrialized modern diet can make them more susceptible to inflammation and may increase the risk of heart disease and cancer.
Reference
Fumagalli et al (2015) Greenlandic Inuit show genetic signatures of diet and climate adaptation Science 349(625): 1343-1347
Kumar Kothapalli, Kaixiong Ye, Maithili Gadgil, Susan Carlson, Kimberly O’Brien, Ji Yao Zhang, Hui Gyu Park, Kinsley Ojukwu, James Zou, Stephanie Hyon, Kalpana Joshi, Zhenglong Gu, Alon Keinan and Thomas Brenna. Positive Selection on a Regulatory Insertion–Deletion Polymorphism in FADS2 Influences Apparent Endogenous Synthesis of Arachidonic Acid Mol. Biol. Evol. (2016)
Holly Reardon, Jimmy Zhang, Kumar Kothapalli, Andrea Kim, Woo Jung Park, and Thomas Brenna (2012) Insertion-Deletions In a FADS2 Intron 1 Conserved Regulatory Locus Control Expression Of Fatty Acid Desaturases 1 and 2 And Modulate Response To Simvastatin Prostaglandins Leukot Essent Fatty Acids. 87(1): 25–33.
07/08/2016 Sanjay Mishra
Human ancestors were largely vegetarian, thus evolving genes that help us thrive on plants. What does this mean for current day omnivores? Find out...
Like chimpanzees, our nearest evolutionary relatives, early hominins were mostly vegetarian. As we evolved, we experimented and adapted to a smörgåsbord of choices. A variety of food sources ensures that we get ample nutrients, especially the essential ones our bodies cannot make, such as Omega 6 and Omega 3 fats. Now, in a study published in the journal Molecular Biology and Evolution, scientists show that evolution adapted us to best use the kinds of fats we get from our diets, but these adaptations can have consequences with changing dietary patterns.
In the body, Fatty Acid Desaturases (FADS) help convert Omega 6 and Omega 3 fats from plant oils or fish and meat to physiologically important long-chain polyunsaturated fatty acids (LCPUFA). Frequent mutations in these genes cause several abnormalities, suggesting that FADS genes are fast evolving. Tom Brenna and Kumar Kothapalli from Cornell University were interested in looking for evolutionary hot spots in FADS, which can be used to trace the origin of the genes and populations.
The team first combed through the International HapMap, a global collection of human DNA sequence variations. In 2012, they discovered a genetic variant resulting in a 22 base pair (bp) insertion / deletion that impaired FADS2, meaning that carriers of the deletion increasingly rely on their diets for LCPUFA.
Conversely, exclusive plant eaters must accommodate for the lack of meat as a source for LCPUFA. “We had the hypothesis that the insertion allele might metabolize the LCPUFA precursors more efficiently than the deletion allele and that vegetarians might have fast metabolizing capacity,” Kothapalli said.
Could the ability to convert plant oils to LCPUFA have evolutionary implications? To find out, Brenna’s collaborators gathered blood samples from vegetarian donors in Pune, India, and omnivorous donors in Kansas, USA and looked for the insertion and deletion in FADS2 using PCR and DNA sequencing.
They found that almost all vegetarians carried the insertion allele, but the deletion was extremely rare. Compared to the omnivore population, almost four times as many vegetarians carried two copies of the insertion allele (I/I). In contrast, about half of the tested US population carried both copies of the deletion allele (D/D).
“It was too good to be true!” Brenna said. “We thought we made a mistake, so we repeated the experiments.” But their results on the evolutionary selection of FADS corresponded perfectly with another study in a Greenlandic Inuit population, which show similar FADS gene selection to accommodate a diet consisting mainly of fish.
Excited by their results from populations with contrasting diets, the scientists then looked for a worldwide pattern by exploring data from the 1000 Genomes Project. They found that the I/I genotype is highest in African and South Asian populations, but lower in European and East Asian populations.
The dramatic difference in the frequency of this FADS2 variant among the ethnic groups prompted Alon Keinan in Brenna’s team to wonder whether the insertion or deletion happened earlier in human evolution. By analyzing related sequences, his team calculated that the insertion allele is ancestral. In fact, both Neanderthals and Denisovans carried this allele.
But does this alter the ability of individuals to make LCPUFA from their diets? Over the next several months, the researchers analyzed the fats carried in volunteers' blood and found that the insertion carriers were better at converting plant oils into omega-6 LCPUFA. While everyone consumed the same amount of plant oil (LA), the insertion carriers accumulated far higher blood levels of the omega-6 arachidonic acid (ARA), which is proinflammatory. Unfortunately, they also made much less anti-inflammatory omega-3 acids – EPA and DHA because their conversion machinery was overwhelmed with producing ARA. This imbalance in omega-6 and omega-3 LCPUFA can have serious health implications. “Of course, Omega-6 is an essential nutrient, but it’s too much of a good thing. That we need to worry about,” Brenna cautioned.
David Katz, Director of the Yale-Griffin Prevention Research Center, who was not involved in this study said the results showcase that, “adaptations that are good in a native context may become a major liability.” These study results imply that for those with a long history of a cultural vegetarian diet, adopting an industrialized modern diet can make them more susceptible to inflammation and may increase the risk of heart disease and cancer.
Reference
Fumagalli et al (2015) Greenlandic Inuit show genetic signatures of diet and climate adaptation Science 349(625): 1343-1347
Kumar Kothapalli, Kaixiong Ye, Maithili Gadgil, Susan Carlson, Kimberly O’Brien, Ji Yao Zhang, Hui Gyu Park, Kinsley Ojukwu, James Zou, Stephanie Hyon, Kalpana Joshi, Zhenglong Gu, Alon Keinan and Thomas Brenna. Positive Selection on a Regulatory Insertion–Deletion Polymorphism in FADS2 Influences Apparent Endogenous Synthesis of Arachidonic Acid Mol. Biol. Evol. (2016)
Holly Reardon, Jimmy Zhang, Kumar Kothapalli, Andrea Kim, Woo Jung Park, and Thomas Brenna (2012) Insertion-Deletions In a FADS2 Intron 1 Conserved Regulatory Locus Control Expression Of Fatty Acid Desaturases 1 and 2 And Modulate Response To Simvastatin Prostaglandins Leukot Essent Fatty Acids. 87(1): 25–33.