Generally when you think about what separates humans from other species, features like upright walking, large brains and language come to mind.

But diet has actually played an enormous role in human evolution. Today at the annual meeting of the American Association for the Advancement of Science, a panel of anthropologists, geneticists and paleontologists got together to discuss how who we are has been shaped by what we eat.

Perhaps the most surprising conclusion was that — despite what some diet gurus may say — there is no “natural” human diet. Not only can humans thrive on a wide variety of diets, from the highly carnivorous fare of nomadic Siberians to the virtually all-potato menu consumed by native Peruvians, but thanks to evolution our species can change its diet surprisingly readily.

“You can find humans living well and healthily from a tremendous diversity of diets,” said William Leonard, an anthropologist at Northwestern University in Evanston, Ill.

But all cultures have one dietary feature in common, said Harvard University primatologist Richard Wrangham — they cook their food. Wrangham believes the advent of cooking during human prehistory was a major evolutionary milestone, because it essentially pre-digested starches and proteins and softened food, helping increase the amount of energy that could be extracted on it. In fact, he pointed out that people in modern technological societies who take up so-called “raw food” diets usually lose substantial amounts of weight.

Many diet books advise following a high-protein, low-carbohydrate diet in order to emulate the eating habits of pre-agricultural humans. Whatever the benefits of such a diet, however, it is clear that in the 10,000 years since the development of farming our genes have responded to the increasing availability of foods such as rice, grains and milk.

“I would say most people who descend from agricultural populations are actually pretty well adapted to a starch diet, because most of the world eats a lot of rice, a lot of corn and a lot of potatoes, said Anne Stone, a geneticist at Arizona State University.

Stone and her colleagues have studied the gene AMY1, which encodes a salivary protein called amylase that breaks down starch. All people have multiple copies of the AMY1 genes. But those from traditionally agricultural populations, such as the Japanese and Europeans, have many more than those from cultures that have never practiced agriculture.

Customers of 23andMe may be able to see the evolutionary effects of an agricultural heritage in their own genetic data. Before people started herding cattle, goats and sheep, the human biological machinery for digesting milk was turned off not long after infancy — perhaps to prevent older children from getting in destructive fights over breast milk. But with herd animals on the scene, when a genetic modification that kept milk digestion functioning into adulthood arose in Europe around 8,000 years ago, it was so beneficial that it eventually spread throughout the continent.

23andMe customers have one modified version of the lactase gene for each A at the SNP rs4988235.

Similar scenarios happened in several other parts of the world as well, so that now many people of European and some of African ancestry can easily digest large amounts of milk.

ShareThis

In the year 1831, two very important events happened to 22 year-old biologist Charles Darwin.  The first was that he boarded the Beagle, a research vessel upon which he would embark on a five-year journey to Central and South America.  There he would collect mountains of data on hundreds of plant and animal species, which he would then use to develop his theory of evolution by natural selection — the cornerstone of modern biology.

The second event was that — just before boarding the Beagle — he fell extremely ill.  Darwin kept his condition secret for fear of being removed from the passenger list.  But this early bout of illness was just the beginning in a series of ailments that would continually affect nearly every aspect Darwin’s life for the next 40 years.

The list of symptoms that plagued Darwin for the majority of his adult life included everything from chronic fatigue, severe abdominal pain, nausea and vomiting, headaches, insomnia, mouth ulcers, boils, anxiety, heart palpitations, and depression (just to name a few).  In his many letters to friends and colleagues, he constantly mentioned the wretched state of his health.  In 1865, he wrote to noted naturalist and friend William Hooker, “I have been [for] five or six wretched days miserable from morning to night and unable to do anything.”  Just a year earlier he had told Hooker, “for five months I have done nothing but be sick.”  His illness often precluded him from many public lectures and events expected of eminent scientists of the time.  His wife, Emma, tried to care for Darwin, as did numerous physicians, but his poor health remained until his death in 1882.

The importance of Charles Darwin as a father of modern biology, combined with the complex and intriguing nature of his chronic illness, have led to many hypotheses as to why he suffered as he did.  Everything from heart disease to arsenic poisoning to a variety of psychosomatic causes have been proposed since his death.  However, it is only within the last several years that these hypotheses have focused on the gastrointestinal symptoms that seemed to plague Darwin most consistently.  Unable to examine the man himself, scientists have pored over his medical records, letters, and personal diaries, in order to posthumously diagnose Darwin’s debilitating illness.

The Case for Lactose Intolerance

During the mid-19th century, lactose intolerance had not yet been described in great detail.  Most gastrointestinal problems were written off as ‘indigestion’ or ‘dyspepsia’.  Indeed, the genetics of lactose intolerance would not be discovered until more than 70 years after Darwin’s death.

People diagnosed as lactose intolerant often suffer severe lower abdominal cramping and diarrhea after consuming milk or other dairy products (including some cheeses and various kinds of cream). Because the majority of Darwin’s symptoms appear to be centered around the digestive tract, a group of researchers from Cardiff University proposed in 2005 that the best explanation for Darwin’s symptoms was lactose intolerance.

It is far more common to find lactose intolerance among South and East Asian populations, though it is not unheard of to find it among Europeans, where it reaches levels of about 8%.  Researchers, digging through his written correspondence, have found many key passages that hint at Darwin being lactose intolerant. For example, in 1865, Darwin wrote to H.B. Jones, his physician, recounting that “on most days, three hours after luncheon or dinner I have a sharpish headache on one side, and with bad flatulence last to the next meal.”  He also wrote to his friend and colleague, William Hooker, “I have had a bad spell.  Vomiting everyday for eleven days, and some days after every meal.”

An analysis of his Diary of Health indicates that foods such as sugar, bacon, butter, and any desserts seemed to intensify his symptoms.  Unfortunately Darwin had a sweet tooth, and the majority of his wife’s recipes involved heavy cream.  To make matters worse, when Darwin was feeling particularly ill he was often given warm milk as a nightcap, a typical remedy during the mid-19th century.  This may have exacerbated his abdominal pain and discomfort.

In fact, the only treatment that appeared to work was something called “hydrotherapy” in which the patient bathed and drank copious amounts of cold water.  Milk was not allowed.  This, some argue, is additional evidence in support of lactose intolerance being the primary cause of Darwin’s symptoms.

The Case for Crohn’s Disease

However, while most agree that the majority of Darwin’s symptoms were gastrointestinal in nature, some remain unconvinced that the best explanation was that Darwin was lactose intolerant.  Instead, they point to a more serious disorder known as Crohn’s Disease.  This new diagnosis is garnering much support within the medical community, in that Crohn’s – even more so than lactose intolerance – accounts for the vast majority of Darwin’s incapacitating symptoms.

Crohn’s disease is a chronic autoimmune disease of the digestive tract.  It is found in about 1-2% of people of European descent, and can affect an individual’s entire digestive system, from the mouth to the anus and everything in between.  Additional symptoms include skin rashes, arthritis, and inflammation of the eye.  It usually first presents itself in early adulthood as a severe gastrointestinal infection.  Individuals suffering from the disease often have a series of flare-ups and remissions throughout their lives.  Crohn’s disease is believed to be a largely genetic disorder, though not all genetic markers have been identified.

Various factors can influence the timing and frequency of flare-ups for sufferers of Crohn’s, including stress, nutrition, and other health issues.  Indeed, Darwin often noted worsening symptoms during periods of high stress, especially when he had to give public appearances or lectures.

Upon close examination of Darwin’s correspondence and diaries by scientists at the University of Chile, his most severe symptoms included abdominal pain and vomiting, but virtually no mention of diarrhea, which is the main symptom of lactose intolerant individuals.  In fact, Darwin had reported regular bowel movements for the majority of his adult life.  It was the abdominal pain, nausea, and vomiting that plagued him for so many years, and these symptoms are key when diagnosing Crohn’s Disease.

In addition, and perhaps more importantly, Darwin had several other health issues seemingly unrelated to the digestive tract, namely skin and eye irritation. Symptoms such as these are often found in patients diagnosed with Crohn’s Disease.  And the fact that there are conflicting reports on the kinds of foods that upset his illness (Darwin also reported getting sick after eating sugar, bacon, and salads), lends additional support that his illness was not related to a specific type of food (i.e. dairy).

There is, of course, the possibility that Darwin suffered from both lactose intolerance AND Crohn’s Disease.  In fact, there is an 83% chance that individuals with Crohn’s Disease are also lactose intolerant.  However, the reverse is not also true, meaning the root cause of lactose intolerance among people with both conditions usually traces back to their Crohn’s.

It also appears that there is some genetic aspect to Darwin’s illness, as many of his family members suffered chronic health problems.  In fact, the Darwin family was famous throughout the 19th and early 20th centuries as having overall poor health.  Darwin’s family history points to some kind of genetic disorder, and the symptoms of Crohn’s disease appear to be the most comprehensive explanation.

The mystery surrounding Darwin’s chronic illness has mystified researchers for over 100 years.  If he were alive today, it is likely that physicians would have no trouble diagnosing what ailed him. And it’s too bad Darwin couldn’t sign up for 23andMe’s Personal Genome Service ^TM! Not only would the father of modern biology be fascinated by his genetic data, but it might have offered a clue to his lifelong illness as well by revealing whether he had a higher risk for lactose intolerance, Crohn’s Disease, or perhaps some other condition.

ShareThis

Art Nouveau architecture at the Codorníu winery outside of Barcelona.

So much new research was discussed in Barcelona it’s hard to decide which were the most notable presentations. But here are a few of the ones I found most interesting:
Were humans shaped more by history or local environment?
A major debate in the human evolutionary genetics talks and posters considered the origin of the genetic differences seen in humanity today: Were they shaped more by populations splitting apart and coming together, or evolutionary adaptation to local environments? Interestingly, people from the lab of our SAB member Jonathan Pritchard presented arguments on both sides. Both talks presented strong evidence using similar data sets. Perhaps one phenomenon has more impact locally and the other more regionally. Certainly the debate continues.

James Cai and coauthors from Stanford (including our very own R&D scientist Mike Macpherson) and The Hebrew University of Jerusalem showed that the history of the human genome cannot be explained simply by neutral variants – variants that do not cause a functional change. All across the genome there is evidence of “selective sweeps” where an advantageous version of a gene quickly increased in frequency in a population or species. For example, the gene FOXP2 has undergone a selective sweep in all humans within the past several hundred thousand years and may have contributed to our ability to use advanced language. More recent selective sweeps in the Duffy and Lactase genes (both have variants that 23andMe customers or demo account holders can read more about in My Gene Journal (now called Health and Traits)) happened after human populations diverged and thus didn’t sweep across the entire globe but are confined to specific regions: primarily western Africa for the Duffy-0 variant and Europe, the Near East, eastern Africa, and southern Asia for Lactose Tolerance.

Selective sweeps tend leave evidence in the form of nearby DNA that gets dragged along with the variant as it sweeps across a population. Similarly, new variants that are disadvantageous (or become disadvantageous when, say, moving into a new environment) can leave these similar signals as they are dragged out of the population. However, it is often difficult to separate out effects of population history from these selective forces. By using a novel statistic that controls for population history, Cai and colleagues show that many locations on the human genome have been affected by these selective sweeps. While previous scans for positive selection required these selective sweeps to be incomplete (see here and here, for example), the authors use a metric which can go back even further to look at the timing and strength of selective sweeps which have affected the entire human population, even going back as far as one million years. This work is an extension of previous research on Drosophila.

Interestingly, one of the data sets used for this work was the complete genome of Jim Watson, who co-discovered the structure of DNA.

Population Structure, History, and Migrations
Sarah Tishkoff of U. Penn gave a talk on her incredible data set of sub-Saharan African populations. So much of the world’s genetic diversity is located in this region, yet its inhabitants have been relatively under-sampled so far. Tishkoff’s data, in the context of global variation, makes it apparent just how important it is to understand the history of sub-Saharan populations in order to understand the history of our species. In one example, Tishkoff used a technique known as Principal Components Analysis (PCA) to collapse all their genetic data into three dimensions. Individuals near each other in PCA are more similar. In her plot, a hunter-gatherer population from Tanzania known as the Hadza can be found in their own dimension on the plot, which suggests that the Hadza, while having a small population size, have been isolated for a long, long time and are quite divergent from other populations, even including the 52 in the CEPH-HGDP data.
Tishkoff also showed how difficult it is to extrapolate from one African population to the next, even if they neighbor each other. One example of this is in parts of western Africa where the Fulani have increased malaria resistance compared to other groups such as the Mossi and Rimaibe – even within the same town.
Several talks and posters looked at the new lactase persistence variants discovered last year in sub-Saharan Africa and the Near East. These variants are functionally the same as their much more common counterparts, which allows Europeans and South Asians to drink milk into adulthood without experiencing lactose intolerance (23andMe customers can look up their genotype for this variant in My Gene Journal (now called Health and Traits)). But because they differ genetically, these newly discovered variants illustrate the importance of milk digestion for populations that relied on herding in their past. Multiple research groups showed that the eastern African persistence variants made their way down to the San Bushmen and neighboring populations of southern Africa.
When normal inheritance breaks down

Genomic imprinting in action. Here, the color of the offspring comes from the father, regardless of which genotype he has.

Andrew Clark of Cornell has been looking at versions of genes in mice that change the traits of offspring depending on whether they are inherited from the mother or father. This phenomenon, called Genomic Imprinting, has been detected in many mammals before, including humans, although interestingly it isn’t found in marsupials or the egg-laying monotremes like the Platypus. However, the traits affected by genomic imprinting have not been surveyed using a genome-wide approach.
Clark and colleagues used the Solexa sequencing platform to look for differences in the mouse brain between mice crossed from two different strains. By switching the strains of the mother and father researchers can detect traits that derive exclusively, or “imprint on”, one parent.
It turns out a good number of genes exhibit genomic imprinting Genes imprinted on the father tend to show only the trait of the father. Genes imprinted on the mother tend to let some of the father’s trait come through, albeit at much lower numbers. In addition, the researchers found differences in the organs affected by imprinting: genes imprinted on the mother were more likely to be expressed in the reproductive organs and those imprinted on the father were found more in the brain.
It appears that imprinting has no immediate benefit for offspring and may have originated in mammals completely by accident, a quirk of our histories. But learning about how imprinting evolved will help us understand how they came to be.

ShareThis