Study under review: Positive selection on a regulatory insertiondeletion polymorphism in FADS2 influences apparent endogenous synthesis of arachidonic acid
Anatomically modern humans first appeared in East Africa nearly 200,000 years ago. Since then, humans have spread out to colonize most of the Earth, forcing adaptation to a wide range of new habitats and climates. These new environments and challenges to our survival likely resulted in powerful selective pressures (the driving forces of evolution and natural selection that alter the survival ability of an organism) on our DNA, leading to new gene variants, and combinations thereof, that were better suited for survival. These gene variants are called alleles, while specific combinations of alleles are called a genotype.
Recent examples of human evolution through natural selection include genetic changes in response to malaria, changes that favor lactose (milk sugar) consumption in adulthood, and changes that regulate brain size. For malaria, the selective pressure was the malaria virus, which increased the survivability of individuals who carried a mutation for sickle cell anemia because this mutation is highly protective against dying from malaria. While selective pressure has occurred throughout human evolution, the agricultural revolution and greater population sizes that began 10,000 years ago have accelerated the rate at which we are able to observe evolutionary changes. The process of natural selection at a genetic level works in two ways. A random mutation could appear that is beneficial in the current environment, or a new environmental stress appears that makes an already existing genotype beneficial to have. In either case, the organism carrying the beneficial allele (whether new or preexisting) has a survival advantage and is likely to reproduce and pass it on to offspring. The chunks of DNA containing a specific set of alleles that tend to be inherited as a unit are called haplotypes, as pictured in Figure 1.
Some of the many genes being explored for variation in modern humans are the fatty acid desaturase (FADS) genes, which code for the enzymes responsible for transforming the shorter-chained omega-3 and omega-6 fatty acids into their long-chained derivatives. Specifically, FADS1 codes for Δ5-desaturase and FADS2 codes for Δ6-, Δ8-, and Δ4-desaturases.
Research has also demonstrated marked genetic variation in the FADS gene cluster between populations. Individuals living in Africa appear to have a FADS genotype that promotes more efficient conversion of shorter-chained polyunsaturated fatty acids into their long-chained derivatives, whereas the Greenlandic Inuit show a genotype that reduces conversion ability. One proposed hypothesis about the mechanisms responsible for these genetic differences is diet. Populations with low consumption of the long-chained polyunsaturated fatty acids, such as Africans, would need enhanced conversion ability to supply the body’s demands. By contrast, the Inuit consume a diet rich in seafood that contains preformed long-chained fatty acids, thus reducing the need for conversion.
The authors of the current study have previously identified a genetic variant in the haplotype called rs66698963. This variation can come in two flavors: with some code inserted (the “I” version) or that code deleted (D). Carriers of two “D” alleles (D/D genotype) displayed significantly lower levels of the FADS1 enzyme than carriers of two “I” alleles (I/I genotype).
Collectively, the above information led the authors of the current study to hypothesize that individuals carrying the D/D genotype of rs66698963 would have a lower metabolic capacity to produce long-chained polyunsaturated fatty acids from precursors than individuals carrying I/I. They were also interested in exploring how global populations differed in their genotype frequency distribution. This is important because if this hypothesis is true, then some people may have to eat more long-chained omega-3 and omega-6 polyunsaturated fatty acids due to a lower capacity to make it themselves. This need may depend on the diet history of your ancestors.
To this day, humans continue to evolve in response to environmental stressors and changes in habitat. One such adaptation is our ability to produce long-chained polyunsaturated fatty acids from dietary precursors, which is influenced by the FADS gene cluster. The study under review sought to determine whether genetic variation in FADS would be associated with long-chained polyunsaturated fat concentrations and how variation differed by population.
Other Articles in Issue #18 (April 2016)
HDL: When good cholesterol breaks bad
LDL is commonly referred to as “bad”, whereas HDL is “good”. Like many other labels, these are oversimplified, especially as HDL-raising drugs have failed. This study explores why that might be.
Interview: Aaron Blaisdell, PhD
Dr. Blaisdell heads up a cognition research lab at UCLA, and is a central figure in the movement to research links between ancestral health and modern health.
High-carb, high satiety?
A common refrain is that carbs make you gain weight, and are too easy to overconsume. Luckily, this line of thinking can be tested in a randomized trial
Peanuts redux: following up on infant peanut exposure
We previously covered a major trial that suggested peanut avoidance was a bad idea for infants at risk of allergy. The researchers continued with those study subjects up to age 6, to see if the results still apply
Does this gluten make me look fat?
Links between gluten and weight gain haven’t been seen so much in observational evidence, but that doesn’t mean they don’t exist. This animal study is one of the first to look at a potential mechanism
Interview: Paul Jaminet, PhD
Dr. Jaminet is the CEO of a promising biotech targeting solid tumors. Here, he explains the science and business behind an innovative potential therapy that targets cancer from a new angle
Add fuel to the fire … or take it away?
Competitive endurance athletes manipulate their carb intake in various ways, and those aren’t always based on evidence. A new carb-cycling strategy may help to shave off precious seconds.
Don’t drink and drive, unless it’s grape juice
Red wine may get all the attention, but grapes (and grape juice) have benefits of their own. This randomized trial tested daily grape juice intake, not just for typical cognitive tests, but also for driving performance
ALA: Alliterative (anti)Longevity Aid?
ALA is used for a variety of purposes, such as for blood sugar control and potential longevity benefits. But this new evidence plants a seed of warning for those taking ALA over long periods of time.