The Human Genome

DNAThe human genome is the complete set of genetic information for humans. This genetic blueprint consists of information encoded as DNA sequences within 23 pairs of chromosomes located in the nuclei of your cells: 23 chromosomes from mum and 23 chromosomes from dad. In addition to this main reservoir of genetic information, each one of us also have a small DNA molecule located in the mitochondria; DNA that are passed on purely from mum to offspring.

A gene is a hereditary unit consisting of a sequence of DNA that occupies a specific location on a chromosome. It’s these sequences we’re primarily concerned with, as it is the instructions in a gene that tell the cell how to make a specific protein. It’s important to note though that most of the genes in the human genome are noncoding DNA that don’t have any important functions at all (that geneticists know of) or are involved in other processes than the synthesis of protein, such as regulation of gene expression and transcription of functional non-coding RNA molecules.

The last mile on the evolutionary road of the human genome

Natural selection, genetic drift, gene flow, and mutations are the mechanisms that shaped the human genome through millions of years of evolution. Of all these processes, natural selection is generally considered the most “important” one. The term natural selection was coined by Charles Darwin in his book ‘On the Origins of the Species’ and describes the gradual process by which heritable biological traits become either more or less common in a population as a function of the effect of inherited traits on the differential reproductive success of organisms interacting with their environment.

When the human and chimpanzee lineages split about 5 to 7 million years ago, hominins started out on a very different evolutionary path than the chimps. The first initial adaptation in the human lineage that set the stage for additional changes was our ability to walk on two legs, a trait that was advantageous for a number of reasons, one of which being that it improved our ancients ancestors’ ability to walk long distances in the search for food.

In the types of ancestral habitats we occupied as hunter-gatherers, those who were not physically fit enough to evade predators, hunt, gather food, and otherwise handle a demanding lifestyle were quickly weeded out of the gene pool. Consequently, over the coming millions of years, natural selection led to the accumulation of various genetic traits that improved our ancestors’ ability to survive and reproduce within the hunter-gatherer niche. This explains why hominins gradually became better at running long distances in the heat, grew larger brains, and developed all of the other features that characterize a well adapted “hunter-gatherer body”.

The first anatomically modern humans appear 200.000 years ago in Africa, and if we are to believe the fossil record, we didn’t colonize the rest of the world until approximately 100.000-150.000 years later. As we travelled into new areas of the world, we had to adapt to habitats that were often very dissimilar to the African savanna. The combination of cultural evolution (e.g., clothing, housing) and Darwinian evolution (e.g., skin pigmentation, body size) helped us adjust to these new conditions.

This migration out of Africa marks a major event in the evolutionary history of man, an event that spurred changes to our lifestyles. However, it’s important to note that it took tens of thousands of years before we reached the far corners of the world, and although we encountered novel environmental conditions, hunting-gathering was still the subsistence mode for all human populations up until the agricultural evolution.

The agricultural revolution approximately 10.000 years ago marks the beginning of profound changes to our milieu, and the rapid cultural evolution that has occurred ever since has completely changed how we eat, move, sleep, and work. In this short evolutionary time there have been only minor genetic adaptations, meaning that our genome is still largely the same as that of our late Paleolithic ancestors.

The vast majority of our genes were selected for in diverse and various ancestral environments that differ markedly from modern environments, and as a result, we now experience a gene-environment mismatch.

Gene expression

The genetic code is often thought of as a static machinery that stays with us throughout life, and few probably pay much attention to how their daily lifestyle choices impact how genes are regulated and expressed. It’s easy to forget that everything is controlled by genes.

Although the actual DNA sequence remains relatively stable, which genes we express (the process by which genetic instructions are used to synthesize gene products) is the result of interactions with the environment.

Besides actual changes in the DNA sequence (think mutations, natural selection, gene flow, and genetic drift), the human body can adapt in at least two other ways to its environment. The first one is epigenetic modifications, a process where decoration of nucleotides results in altered gene expression (1, 2). The second is changes in gene expression in a period of hours, days, or weeks (1).

Although the research on epigenetics is still in the early stages, there is already enough evidence to suggest that some epigenetic marks are heritable, meaning that you could pass on “parts of your environment” to your offsprings through genes (23).

What all of this means is that although your actual genetic code stays the same, how you express your genes is largely a result of the types of stimuli you subject your body to.

A western lifestyle adversely affects gene expression

Several studies show that insufficient sleep, physical inactivity, consumption of highly processed food, and many other factors associated with modern lifestyles promote abnormal and suboptimal gene expression (1, 23, 4, 5). When you think about it, this is just the response one would expect, as our genes were primarily selected for when we lived as foragers in the wild, a way of life that involved regular physical activity, consumption of nutrient-dense whole foods, regular sun exposure, etc. We are still – to a significant extent – genetically adapted to a hunter-gatherer lifestyle (6, 7).

You don’t have to look further than at the people around you on the street to understand that the gene expression pattern of most people in the modern world is very different from that of hunter-gatherers and healthy non-westernized populations. In affluent nations such as the U.S., the majority of people are either overweight or obese, and many other chronic disorders – many of which are related to obesity – have increased dramatically in prevalence recently.

Not only will a lifestyle that is at odds with your ancient biology promote an abnormal gene expression pattern, but it could also leave epigenetic tags on your genes, which might be passed on to your children (23).

The bottom line is that a western lifestyle can produce changes in gene expression that often pass a clinical threshold into a chronic disease phenotype.

Normalizing gene expression

Hunter-gatherers and some traditional, non-westernized populations (both contemporary and prehistoric) don’t know about DNA, gene expression or natural selection – and in a sense, they don’t have to. They live in environments that closely resemble those our ancestors evolved in for millions of years, and although different indigenous populations occupy dissimilar habitats, their lifestyles retain most of the features that characterize the lifestyle of our preagricultural ancestors (6, 8). Perhaps most importantly, they eat Paleolithic or traditional diets, engage in a lot of physical activity, spend plenty of time outdoors, and get sufficient sleep.

Hunter-gatherers are lean and free from many chronic, degenerative disorders because they follow a diet and lifestyle that are better matched with our genetic blueprint (6, 8, 9). That doesn’t mean they don’t get sick from infectious diseases and often have high rates of infant mortality, it just means that we can learn a lot from our past about how to live in the present.

So, how can we upregulate our ‘good’ genes and downregulate our ‘bad’ genes? The obvious answer is that we should look at nutrition, exercise, and health through the lens of evolution to get a better understanding of what types of stimuli the human body is adapted for – an understanding we can combine with modern science to shape our lifestyle in the 21st century.

These elements are on top of the list of lifestyle factors that help “normalize” gene expression:

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