How chimpanzee and human diets affect gene expression

Even though I read the classic 1975 Science paper by Mary-Claire King and Allan Wilson, where they demonstrated through comparative protein analysis, that chimpanzees and humans are genetically 99% identical, I was still shocked to read the results of the initial draft of the chimpanzee genome when it came out in September 2005. Like many others, I understand chimps to be the closest living relative of humans in the natural world. The similarities we share in behavior, morphology, personality, and culture are phenomenal… But to read that 96% of total the human genome is identical to the chimpanzee genome, well, I was floored with that statistic to say the least.

Since then, many studies have elucidated that the phenotypic differences between humans and chimpanzees are due to differential gene expression. The foremost study on this subject, that comes to my mind, is Yoav Gilad’s 2005 paper, “Expression profiling in primates reveals a rapid evolution of human transcription factors.” I would also check out important 2005 paper, “Parallel Patterns of Evolution in the Genomes and Transcriptomes of Humans and Chimpanzees.”

In the Gilad paper, he and his coauthors used novel gene-array technology to measure the extent of gene expression in thousands of genes simultaneously. Their study showed that as humans diverged from their ape ancestors in the last five million or so years, genes for transcription factors, which are proteins that control gene expression, were four times as likely to have changed their own expression patterns as the genes they regulate. So basically any small changes in the expression of these regulatory genes can have an enormous impact, because they influence the activity of their downstream gene product. I’m not one toot my own horn, but if you are still confused by this summary I apologize… I don’t have a better way to explain what and how differential gene expression is better than this comment I left in April 2007.

That being said, I’ve been wondering what causes differential gene expression for quite sometime. I know many different stimuli can activate and repress gene expression, from cell signaling to environmental shifts such as climate change or drought. But I wondered how differential gene expression can be manifested to cause such a massive difference between genetically similar humans and chimpanzees. Could it be due to the alignment of the moons of Saturn, or are there more tangible things… like diet, that cause differential gene expression?

Much of anthropology currently thinks that one of the identifiable human traits is a dietary divergence. That’s why I’ve kept a keen eye on the work of David Strait, who is investigating fossil morphology of early hominins to check out how changes in morphology and diet change go hand and hand. I’ve also been following Nate Dominy‘s work, which is much more applicable from a genetic perspective because he’s looking at genes such as AMY1, a salivary enzyme, and how humans have a different copy number compared to other primates. But by in large, my question has been unanswered.

Fast forward to today, when I catch this headline from PLoS One, “Human and Chimpanzee Gene Expression Differences Replicated in Mice Fed Different Diets,” in my RSS feeds. Before I even read the abstract, I thought to myself, “Wow, here it is… A paper to answer it once and for all.” You know you’ve heard the cliche phrase, we are what we eat… now it seems that a group of scientists from China have grouped up with Svante Pääbo, the man whose dominating anthropology authorship, to investigate how the different diets of chimpanzees and humans affect gene expression.

Because of logical and ethical issues, actual humans and chimpanzees were note subjected to experimental conditions and sacrificed to determine the differences in gene expression. Instead, four groups of six young mice were feed four different diets for two weeks. Here’s a summary of the diets given to the respective four groups. You’ll get a kick out of the last one.

  1. Ye old mouse pellet diet, high in calories and proteins and heat processed to yummy goodness.
  2. Veggie, fruits, and yogurt — similar to what captive chimpanzees get.
  3. Human cafeteria food.
  4. The Supesize Me diet. Yes, exclusively McDonald’s fast food.

After the two weeks, the mice were killed and the expression levels of brain and liver tissue was analyzed and compared. Right off the bat, no significant expression difference was noticed in brain tissue between the mouse, veggie, and cafeteria diets. Only did the Supersize Me diet affect brain gene expression!. Whoa, does that mean human and chimpanzee brains operate similarly? Likely, we know the brain utilizes glucose for metabolism… so long as you’re getting a source of carbohydrates, the brain should be functioning more or less just fine. But high fat diets affect the hippocampus, and polyunsatturated fatty acids hamper learning. All the differences in gene expression was observed in the liver, the organ that makes a lot of metabolites and stores glycogen storage.

The second observation was that the cafeteria and McDonald’s diets have indistinguishable expression differences. They clumped these two diets together, and compared them to the mouse and chimpanzee diets. When comparing the human diets to the mouse diet, no significant overlaps of expressed genes were observed. That’s probably because the human diet induces a much different effect on mouse liver genes. When comparing the human diets to the chimpanzee diet, a total of 117 different genes were expressed, specifically upregulated in the human diet. The expression level of these 117 genes was compared between orangutans and chimpanzees, who have much similar diets, and it was noted that they also have a similar expression level. In other words, the human diet causes 117 genes to turn on.

What’s really cool, and what really ties into a paper I reviewed a couple days, is that the authors found out that the promoter regions and the amino acid sequence of these 117 upregulated genes evolved faster than other genes. The authors suggest,

“…that changes in dietary regimes may have caused some genetic adaptations in the human and chimpanzee genomes. That dietary changes can result in genetic adaptations is illustrated… It is conceivable that certain dietary changes in human evolution, such as increased nutritional quality and a reduced need for detoxification due to the introduction of cooking, have caused a relaxation of selective constraints on diet-related genes.”

The indistinguishable expression differences seen in the livers of mice fed the cafeteria and McDonald diets is one of the most intriguing observations. Could some commonality in the diets, such as cooking, be causing this similar expression pattern? Possibly. Does that mean the advent of cooking food caused hominids to turn a major evolutionary corner about 1.9 million years ago? I’m sure Harvard professor, Richard Wrangham, would like to know, he’s the one that proposed in his 1999 paper, “The Raw and the Stolen. Cooking and the Ecology of Human Origins,” that cooking tubers is linked to changes in body size and tooth size that separated Homo erectus from earlier australopithecines (also something Strait is looking at!).

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