There is a rich history of philosophers and scientists asking questions, such as: “Who am I, where did I come from and who am I related to? Modern technology enables us to analyze the DNA in our 23 pairs of human chromosomes. Many people think that our DNA controls much of who were are, such as our physical appearance, intelligence and many innate abilities. Some even think that it defines our race or ethnicity. Some of these people would also agree with the saying, you are what you eat, even though that would actually be a contradiction. That is, our diets affect our physical and mental health. In this article, I will address these questions. I will describe some basic assumptions that are we learned as children, such as we exactly inherit half of our genes from each parent and we can trace our ancestry back thousands of years. Then, I will show how this is an oversimplification on one level and absolutely wrong at a deeper level.
Genealogy and common ancestors
Currently, genealogy is big business and a very popular hobby. Over 100 million DNA tests were sold in 2021. Many people want to know where they fit into the tree of life. The sequences of bases in their DNA can be compared to those from people from all parts of the world. You might discover that you are related to a famous person in history, like Charlemagne. To do this, some basic assumptions are made. We assume that we get exactly half of our DNA from our mother and the other half from our father. Based on this, the fraction of our DNA that came from our recent ancestors is 1/2n, where n is the number of generations. That is, we get 1/2 of our DNA from each of our two parents, 1/4 from our each of our four grandparents, and 1/8 from each of our eight great-grandparents. In this process, we say that DNA and genes are transferred vertically from parents to children.
This predicts that we can go back many more years and find some interesting ancestors. About 150 years ago, we had 64 great-great-great-great-grandparents. We were descended from 64 different people. By the 33rd generation (about 800 to 1000 years ago) we have more than eight billion ancestors. That is more than the number of people alive today, much larger than the world population a millennium ago1. Still, this assumes that mating is random and that populations intermingled constantly. In fact, Homo sapiens are somewhat inbred. In isolated communities, distant cousins that share only 1% of their DNA often marry and beget children. Their most recent common ancestor would have lived over 150 years ago. Moreover, many of one’s ancestors can occupy multiple places in one’s family tree. Your great-great-great-great-great-grandmother might have also been your great-great-great-great-aunt1. When you consider older generations, you reach a date when our family trees share not just one ancestor in common, but also every ancestor. You reach a genetic isopoint, at which the family trees of any two people on the earth now, trace back to the same set of individuals. People who were alive at the genetic isopoint were either the ancestor of either everyone alive today or no one alive today. Humans left Africa and began dispersing throughout the world at least 120,000 years ago, but the genetic isopoint occurred much more recently—somewhere between 5300 and 2200 B.C., according to mathematical modeling and computer simulations by a group of statisticians led by Douglas Rohde2. They recognized that the random mating model ignores essential aspects of population substructure, such as the tendency of individuals to choose mates from the same social group, and the relative isolation of geographically separated groups. When this was included in the model, they were able to estimate the genetic isopoint. This suggests that the genealogies of all living humans overlap in remarkable ways in the recent past2.
This utterly demolishes the concept of different races and pure lineages of humans1. Nobody has ancestors from just one ethnic background or region of the world1. Race is a social construct with no scientific basis. There is only one race – the human race.
There is another complication when trying to determine one’s genealogy, recombination. We don’t really inherit exactly half of our DNA from each parent. Parts of the DNA in the chromosomes from each parent break apart and recombine upon production of the zygote, or fertilized ovum. This causes random reshuffling of genes in each successive generation. So, some of one’s ancestors contribute disproportionately to their genome, while others contribute none. Our genetics does not accurately reflect our genealogy when we go back a few generations. Moreover, our genetic code is not a static entity. Some parts of a chromosome can change their position within the genome. This was discovered to occur in maize (by Barbara McClintock in 1956) 3. She called them jumping genes. Her were results were ignored, partly because she was a woman. Fortunately, she did win the Nobel Prize in physiology or medicine in 1983 for her seminal work.
There are many such transposable (mobile) genetic elements in our DNA. This is true of many plants and animals. A large fraction of the genomes of their eukaryotic cells is made up of transposable elements4. They are interspersed repeats with a high copy number. This is because they have entered genomes countless times throughout evolutionary history4.
Recombination of genes
Humans have two copies of chromosomes 1 – 22 (the autosomal chromosomes) and two sex chromosomes. The cells are diploid. Almost all females have two X chromosomes and males have one X and one Y chromosome. However, some people have more than two sex chromosomes. Some people have two X chromosomes and one Y chromosome. The chromosomes contain DNA that is made up of four bases, adenine, thymine, guanine and cytosine, arranged in a double helix. The DNA in some parts of our chromosomes is transcribed into messenger RNA (mRNA), which leaves the cell nucleus and enters the cytosol of the cell. The mRNA is translated into proteins on ribosomes that are located in the cytosol. Human cells have about 23,000 protein-coding genes. Moreover, DNA recombination occurs when a section of DNA from one chromosome is exchanged with DNA from another chromosome by cutting and pasting. It usually occurs between regions of similar base sequences.
For sexual reproduction to occur in humans, sperm and ova must be produced through reduction division of parent diploid cells. That is, the diploid parent cells undergo one round of DNA replication, followed by two separate cycles of cell division to produce four haploid cells (sperm for males and ova for females). When chromosomes from a sperm and ovum unite to form a fertilized egg, some recombination occurs5.
However, not all our DNA came from human ancestors. When viruses and bacteria infected our distant ancestors, some of their DNA recombined with the human chromosomes. This is called the horizontal transfer of DNA. Much of our DNA contains remnants of ancient viruses.
So, the rhizome of life is probably a better metaphor than the tree of life. Rhizomes are modified underground plant stems that send out roots from their nodes. Some species of bacteria can form colonies in roots and rhizomes. For example, Rhizobium and Bradyrhizobium colonize the roots of legumes, triggering the formation of nodules which attract more of these photosynthetic bacteria. The bacteria convert atmospheric nitrogen gas (N2) into ammonia (NH3), which the legumes can use to make leaves in this symbiotic relationship.
Similarly, bacteria and viruses can enter all branches of life and integrate their DNA into them. So, the DNA in all species is actually a mosaic of gene sequences with a variety of origins. Genomes are collections of genes with different evolutionary histories that are not well-represented by a single tree of life. At the same time, many genes have several different origins due to recombination. Bacteria and Archaea routinely transfer genes laterally from one species to another. Also, pieces of viral DNA and RNA may be the sources of retrotransposons that make our human brains much different than that of other primates. Bacteria and many types of viruses have DNA, which is transcribed into mRNA and then translated into proteins. Other viruses (like the HIV and SARS-CoV-2 viruses) have RNA instead of DNA. Their RNA is reverse transcribed from DNA. Retrotransposons are DNA sequences that share a homology with retroviruses that have RNA that is reverse transcribed into DNA when the virus is replicated.
Retrotransposons were crucial for the emergence of mammalian, primate and human brain morphology and function4,6. About half of the nucleotides in the human genome are parts of retrotransposons7. L1 retrotransposons are active in the hippocampus and caudate nucleus in the human brain and may account for much of the differences that are seen in so-called identical twins (actually, monozygotic twins). Retrotransposons are also important in generating new neurons throughout life in the hippocampus. L1 retrotransposons are also used in the developing human brain, in which new neurons are constantly being made. On the other hand, L1 insertions occur in genes that are commonly mutated in cancer. So, we are changing the way we think about the origins of life and its diversity.
You are what you eat. About 99% of the protein-coding genes in our bodies are from bacteria in our guts
Even though many people look for the identities through genealogy, we often hear the saying, “You are what you eat”. That is, our diets affect our health. A healthy diet based primarily on plants will support the immune system and help to prevent obesity and diseases of aging. This includes most types of cancer, as well as diabetes, cardiovascular diseases, dementia and neurodegenerative diseases. One way that this happens is by producing a healthy gut microbiome and enteric nervous system8,9. Fresh fruits and vegetables, as well as whole grain bread and pasta provide dietary fiber that helps form a healthy gut microbiome (the collection of all the microorganisms in the gut). The contents of our intestinal tracts belong to our bodies. It is a mutualistic, symbiotic relationship. In contrast, red meat tends to increase the levels of dangerous bacteria like Fusobacterium nucleatum, which causes DNA damage and genomic instability within developing tumors. This type of bacteria stimulates inflammation and can protect tumors from being identified and destroyed by the immune system. This increases the risk of cancer spreading. Dysbiosis in the gut microbiota-gut-brain axis plays important roles in aberrant social behavior as well as the etiology of several neurodegenerative diseases, including anxiety, depression, autism and Parkinson’s disease. On the other hand, vegan and vegetarian diets as well as the Mediterranean diet help build a healthy gut microbiome8,9.
Diet, exercise, mood, overall health and stress can change the concentrations of hormones that affect the gut microbiome. The opposite also occurs. A healthy gut microbiota can help keep a person calm because bacteria affect the concentrations of stress hormones (corticosterone and adrenocorticotropic hormone, or ACTH). On the other hand, dysbiosis in the gut microbiome can contribute to autoimmune diseases, including type-1 diabetes9. This inter-kingdom form of communication has been called microbial endocrinology. For example, the stress-mediated excretion of neurohormones can alter the expression of genes in pathogenic bacteria in the gut. Hormones and neurotransmitters affect many aspects of behavior, which is not simply hard-wired in the brain that is in one’s skull. Our health and behavior also depend in part on the gut microbiome – our second brain. As a result, our behavior and mental skills are influenced by our lifestyle, diet and exposure to antibiotics. They are not hard-wired by the genes we inherit upon conception9.
Often, I’m asked why I don’t have my genealogy determined. Don’t you want to know who you are? My answer is, “I already know that I’m almost 100% American”. The bacteria in my gut come from the food that I eat, which almost exclusively comes from somewhere in the Americas.
Actually, the truth is that my genetic information is constantly changing. There is a layer of control that lies above genetics. It’s called epigenetics. That is, our DNA can be modified before it’s transcribed into mRNA and translated into proteins. The proteins can be modified as well when the internal or external environment requires it. The transcription and expression of genes must be turned on and off at the right times to maintain the many rhythms of life. I am not the same person in the morning that I am at night. I will not be exactly the same person tomorrow as I am today.
1 Hershberger, S. Humans are more closely related than we commonly thought. Scientific American, 2020. 5 Oct. 2020.
2 Rohde, D.L. et al. Modelling the most common ancestry of all living humans. Nature, Volume 431, p. 562-566, 2004.
3 McClintock B. Controlling elements and the gene. Cold Spring Harbor Symposium Quantitative Biology, Volume 21, p. 197–216, 1956.
4 Ferrari, R. et al. Retrotransposons as drivers of mammalian brain evolution. Life, Volume 11, article 36, 2021.
5 Williams, M. and Teixeira, J. A genetic perspective on human origins. Portland Press, 2020.
6 Coraux, R. and Batzer, M.A. The impact of retrotransposons on human genome evolution. Nature Reviews Genetics, Volume 10, p. 691-703, 2009.
7 Lee, G. et al. Landscape of somatic retrotransposition in human cancers. Science, Volume 337, p. 967-971, 2012.
8 Smith, R.E. Don’t eat meat! Save yourself and humanity. Wall Street International, 24 October, 2018.
9 Smith, R.E. Our second brain. The enteric nervous system and gut microbiome. Wall Street International, 24 July, 2019.