If the Nucleus is Not the Mind of the Cell, Then What Is It?

The human genome project not only uncovered just how complex the sequence of DNA is in living organisms but revealed that the majority of organisms found here on Earth have very similar, if not virtually identical, genomes. Did you know we have 99.9% of the same genome as bananas?! Another research model that scientists have used to compare our genomes is the worm, where, you guessed it, our genomes are very similar. But the number of genes that we express compared to a worm or a banana is substantial. In the past, researchers have claimed that humans are estimated to express 80,000-100,00 genes approximately.¹ However, as of 2020, the overall tally of more than 21,000-25,000 protein-coding genes is a substantial jump from previous estimates, which puts the figure at around 20,000.1 Now, let’s compare this to a number found in a worm, intuitively we’d think there are fewer genes, right? The primitive Caenorhabditis worm serves as the perfect model for studying the role of genes in development and behavior. This rapidly growing and reproducing organism has a precisely patterned body comprised of precisely 959 cells and a simple brain of about 302 cells. However, the Caenorhabditis worm contains approximately 24,000 Caenorhabditis worm genes. The human body is comprised of 50 trillion cells yet only has 1,000 more genes than this lowly spineless microscopic worm!² This means that there is not much difference in the total number of genes found in humans and those found in primitive organisms. Additionally, we do not gain our complexity over worms and plants by using more genes: fewer complex organisms do not correlate (recall the comparison of correlation to cause and effect) with less complex organization.

We were taught in medical school that more complex organisms contain more complex genomes, but as was just mentioned, this is not true. Another common misconception that we were taught was that the nucleus is the true brain of the cell. If our assumption that the nucleus and its DNA-containing material is the brain of the cell, then removing the nucleus (known as enucleation) would result in the immediate death of the cell, right? Well, this is what researchers did where they used micropipettes to remove the nucleus from cells. And guess what? Following enucleation, many cells survived for up to two or more months without genes. They were viable enucleated cells and did not lie around like brain-dead lumps of cytoplasm. They were actively ingesting and metabolizing food, they maintained coordinated operations of their physiological system, and they retained their ability to communicate with other cells.

Furthermore, they were able to engage in responses to growth and protection requiring environmental stimuli. But enucleation was not without side effects, of course. Without their genes, they could not divide; thus, they were not able to produce any protein parts that they would have lost through normal wear-and-tear. Therefore, the inability of the cells to replace these small proteins contributed to mechanical dysfunction and ultimately resulted in the death of the cell. This is similar to the concept of oxidative damage in your body and how it replaces damaged cells with new cells, which happens every few days in your stomach lining, for instance, believe it or not.

The researchers noted, “Our experiment was designed to test the idea that the nucleus is the brain of the cell. But if the cell had died immediately following enucleation, the observations would have at least supported the belief, but the results were unambiguous.” Enucleated stem cells still exhibited a complex coordinated life-sustaining behavior. It implies that the cell’s brain is still intact and functioning.³ If the nucleus and its genes are not the cell’s brain, what exactly is the DNA’s contribution to a cell? The enucleated cells died not because they lost their brain but because they lost their ability to reproduce. Meaning enucleated cells cannot replace failed proteins, building blocks, nor replicate themselves. Therefore, the nucleus is not the brain of the cell; it is the gonads! It is the reproductive organ of the cell, not the brain. HUGE INFORMATION. Additionally, when scientists took out the DNA, they studied the DNA, and most of the scientists threw away the proteins thinking that it was junk because they surmised it did not contain any data. It was like throwing the baby out with the bathwater. But now, epigeneticists are bringing back the baby and studying the chromosome’s proteins because proteins are turning out to play a crucial role as the genetic information of DNA.

Furthermore, the science of epigenetics (literally meaning control above genetics) profoundly changes our understating of how life can be controlled. And within the last decade, epigenetic research established that DNA blueprints passed down through genes are not set in concrete at birth. Our genes are not our destiny. Environmental influences, nutrition, stress, and emotions can all modify your genes without changing the blueprint. How does that happen? I’m going to explain this to you very easily. Dr. Lipton uses a perfect analogy of a television set to understand the relationship between epigenetic and genetic mechanisms easier to digest.

Inside of the nucleus, chromosomal DNA is tightly packaged into what looks like a clump of yarn with the help of a specific protein called histones. Along with histones, regulatory proteins further ensure that the DNA is tightly wound up, covering the DNA (much like how a long sleeve shirt covers your arm), preventing any genes from being read.

Let’s use an example and get nerdy for a second. The blue eye gene is encoded by a gene called OCA2. The OCA2 gene is located on the long arm (q) of chromosome 15, specifically from base pair 28,000,020 to base pair 28,344,457 on chromosome 15. Imagine your bare arm is the OCA2 gene but is covered by bound regulatory proteins like a shirt sleeve, making it impossible to read. How do you get the sleeve off? You need an environmental signal to spur the sleeve protein to change shape (remember when we talked about proteins changing their confirmation, providing them free rotation around the polypeptide bond?) and detach from the region of the DNA containing the OCA2 gene such that the gene can be read. Once the DNA is uncovered, transcription proteins make a complementary copy of the OCA2 gene. As a result, the gene’s activity is now “controlled” by the presence or absence of these sleeve proteins, which are now controlled by environmental signals.

Back to the analogy of the test screen I mentioned earlier. Think of the pattern of a test screen as a pattern encoded by a given gene. The dials and switches of the TV fine-tune the test screen by allowing you to turn it on and off, modulating several characteristics, including volume, color, hue, contrast, brightness, and vertical and horizontal holds. By adjusting the dials, you can alter the appearance of the pattern on the screen while not changing the original broadcast pattern.

Another example can be shown through a particular type of mice species known as agouti mice. In one study, scientists looked at the effect of dietary supplements on pregnant mice with the abnormal “agouti” gene. Wild-type agouti mice have yellow coats, are very obese, and have a high predisposition to cardiovascular disease, diabetes, and cancer. In this study, one group of yellow agouti mothers received methyl-group rich supplements, such as folic acid, vitamin B12, betaine, and choline, while another group of pregnant mice with the abnormal “agouti” gene did not. Methyl-rich supplements were chosen because several studies have shown that the methyl group is involved with epigenetic modifications. When methyl groups attach to a given gene’s DNA, it changes how chromosomal regulatory proteins bind to the DNA molecule. If the proteins bind too tightly to the gene, the protein sleeve cannot be removed; thus, the gene cannot be read. Methylating DNA can silence or modify gene activity; this is one of the hallmarks of epigenetics. The mothers who received the methyl-rich supplements produced standard, lean, brown mice, even though their offspring had the same agouti gene as their mothers. The agouti mothers who did not get the supplements produced yellow pups, which ate much more than the brown pups. Therefore, two groups of agouti mice that were genetically identical had radically different litters in appearance, all because of an environmental signal’s influence on the genome.⁴

Lastly, let’s discuss the topic of “dark DNA” also known as introns. Here’s another astounding finding that came out of the Human Genome Project: genes that encode a cell’s protein building blocks, known as exons, constitute less than 2% of the genomes total amount of DNA, so the vast majority of DNA does not contribute to the cell’s protein population. The belief that this DNA lacked function led Francis Crick to label it as “junk DNA.” Though readily accepted by the public, that term irritates large numbers of biologists who cannot fathom the idea that cells carry massive amounts of useless DNA. That’s why geneticists prefer to use the term dark matter, dark DNA, or introns when referring to non-coding DNA. Bent on unlocking the mysteries of dark DNA, a consortium of genetic scientists created the Encode Project to assess the function of junk DNA. Their research revealed that over 80% of non-coding DNA regulates the production and assembly of gene-encoded proteins. A significant discovery also found that dark DNA contains mechanisms by which environmental information could modify the readout of protein-encoding genes. It turns out that dark DNA uses epigenetic mechanisms that enable a human cell with 19,000 blueprints to code for over 100,000 different protein molecules!⁵

This answers the question as to how humans with 21,000-25,000 protein-coding genes have a similar number of protein-coding genes as underdeveloped organisms on the evolutionary totem pole. Yet, we have so many more proteins that we must make. Well, this is where our dark DNA comes into play. Introns and exons are controlled by epigenetic factors: environment and proteins. Hence, allowing the genome to express so many different proteins in our body. That’s how we became so complex as human beings. This is similar to using an erector set or Lego blocks, you have the same building blocks, but you’re arranging them differently. The blueprint for each organism is encoded in the dark DNA, which is directly connected to the dynamic environment through epigenetic mechanisms. Such mechanisms allow us to interpret, translate, and control the activity of these protein-encoding genes. What do you guys think?! Any questions? Please comment below!