Almost 70 years after Watson and Crick, what have we learned about humans and DNA?

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66 years ago today, you might have picked up a copy of the scientific journal Nature and flipped to page 737. If you had, you’d be staring at some freshly minted history and, for most people, it would be wholly unimpressive. Barely extending beyond a page, the article you’d find there is entitled: A Structure for Deoxyribose Nucleic Acid [1]. There’s no new experimental evidence provided, and only one figure. Though it’s short, its impact was immense: The authors, James Watson and Francis Crick, provided a theoretical structure for the life giving molecule known as DNA.

Nowadays, we often take it for granted that we know what DNA is and what it does. Almost anyone can have their DNA sequenced, and then use that information to learn about their potential risks for conditions like breast cancer, or Alzheimer’s. Most people understand that our DNA links us to one another and can tell us where our ancestors may have lived thousands of years ago. But when Watson and Crick’s paper was published in 1953, buoyed by the work of Rosalind Franklin, they knew none of that. We’ve come a long way since then. In honor of DNA Day—the holiday commemorating their seminal paper—we thought we’d reflect on just how much we’ve learned over these past six decades.

DNA and cancer are closely linked

Researchers have found that one person’s DNA can differ from another’s (usually differing in about 3.2 million locations on average). Sometimes, these differences occur in parts of our DNA that protect us from cancer. One such location is known as BRCA1, a gene whose DNA sequence tells our body how to build the BRCA1 protein. In the early 1990s, a team of scientists led by Mary-Claire King announced that specific changes to the DNA coding for BRCA1 could significantly increase a person’s risk for specific types of breast cancer [2]. In the years that followed, numerous other locations in the DNA were found to increase or, in some cases, decrease a person’s odds of developing cancer [3].

We’ve come a long way since Watson and Crick

Humans have known about breast cancer for centuries, but treating it—much less preventing it—was not very effective [4]. Fortunately, DNA can now be used to identify those who are at an increased risk of developing breast cancer and, in some cases, possibly even prevent it.

The blurry line between Neanderthals and us

In the early 1800s, a series of skeletons were discovered throughout Europe. Though they appeared to be human, they were… different. The brow ridge, for example, was much more pronounced, and they didn’t seem to have a chin. Years of debate led to the conclusion that these skeletons belonged to a related species of hominin, now known as Homo neanderthalensis.

On the tree of life, with its many branches depicting the evolutionary relationship between different species, Neanderthals occupy the branch closest to ours—or so we thought. In the late 1960s and early 1970s, researchers began to use genetics as a way to understand how people are related to one another, as well as how species are related to one another [5,6]. Population geneticists learned that they could identify patterns in the DNA sequences of people from one population, like Europeans, that were slightly different from more distant populations, like Americans. This eventually lead to ancestry testing as we know it—something Watson and Crick may only have dreamed of.

Around the same time, similar studies were exploring how modern humans relate to other species. These studies have found that the tree of life is less of a tree, and more of a tangled bush6. Put another way, the evolution of modern life has not been a simple linear progression. Emblematic of this was the recent revelation that Neanderthals, often characterized as fumbling cavemen, may not have been a different species at all. In fact, many people alive today inherit a small amount of Neanderthal DNA.

DNA evidence suggests that Neanderthals may have initially begun to form a different human species, likely due to significant amounts of time separated from the groups of humans that would eventually be known as modern humans. But not enough time had passed. About 100,000 years ago, modern humans left Africa and encountered Neanderthals. The fact that they were able to integrate and form hybrid humans suggests that Neanderthals weren’t a definitively different species [7]. This surely would have been news to Watson and Crick.

A foreign passenger lives within us

Mitochondria, the “powerhouses” found in most of our cells, are tiny structures that provide cells with energy. They are absolutely vital to our health. In fact, almost every life form that can be seen with the naked eye relies on mitochondria (or a related structure) for survival. Scientists have known about these microscopic power plants for a long time, but it wasn’t until recently that we learned of their surprising origins.

Mitochondria, it turns out, used to live on their own as a type of bacteria. But billions of years ago, they likely invaded another bacteria-like organism. Finding shelter there, the mitochondrial ancestor was able to survive longer and provide its host with energy. It’s not clear exactly how it all went down, but researchers have found that mitochondria have their own DNA and that patterns within that DNA indicate bacterial origins [6,8].

Humans have around 20,000 different genes

The early 1900s saw a rush of scientific discovery, including the finding that DNA was the biological material that carries genetic information from one generation to the next. What we didn’t know was just how much information was contained in our DNA. We had long known that discrete units of genetic material—genes—were responsible for influencing our traits. But how many genes does one person have? When Watson and Crick published their paper, the notion of sequencing an entire genome was little more than fantasy. But that’s what it would take to truly identify how many genes we have.

The human genome is 500x longer than the Harry Potter book series

As DNA sequencing technology improved, it became clear that we would eventually be able to accomplish this lofty goal. That day came in 2003, 16 years ago today, when the Human Genome Project published the full human DNA sequence—almost every one of its 3.2 billion letters [9]. To give you an idea of how big that is, 3.2 billion letters is equivalent in length to 507 copies of the complete Harry Potter book series (books one through seven)!

So, how many genes were in there? It’s hard to say, exactly. What defines a gene is ambiguous, but scientists generally agree that there are close to 20,000 identifiable genes in our DNA which combine to influence our traits (everything from hair color, to insulin production, to height). The precise number is in a state of flux, because we’re still adding and subtracting genes as we learn more about the complex workings of the human genome [10].

Now, 66 years after Watson and Crick’s paper appeared in Nature—and just 16 years after the human DNA sequence was published—we know more about DNA than we ever have. With so much growth in such a short time, it’s exciting to look to the future and think about what we might be able to do with DNA in another 66 years.

References

1. James Watson and Francis Crick. “A structure for deoxyribose nucleic acid” Nature 171 (1953): 737–738. Web. 23 April. 2019.

2. Hall, J M et al. “Linkage of early-onset familial breast cancer to chromosome 17q21” Science 250.4988 (1990): 1684-1689. Web. 23 April. 2019

3. “Oncogenes and Tumor Suppressor Genes.” American Cancer Society, www.cancer.org/cancer/cancer-causes/genetics/genes-and-cancer/oncogenes-tumor-suppressor-genes.html.

4. Mukherjee, Siddhartha. The Emperor of All Maladies a Biography of Cancer. Gale, Cengage Learning, 2012.

5. Woese, C R, and G E Fox. “Phylogenetic structure of the prokaryotic domain: the primary kingdoms.” Proceedings of the National Academy of Sciences of the United States of America vol. 74,11 (1977): 5088-90.

6. Quammen, David. Tangled Tree: a Radical New History of Life. Simon & Schuster, 2019.

7. Rogers, Alan R., Ryan J. Bohlender, and Chad D. Huff. “Early History of Neanderthals and Denisovans.” Proceedings of the National Academy of Sciences of the United States of America 114.37 (2017): 9859–9863. PMC. Web. 19 Oct. 2018.

8. “The Origin of Mitochondria.” Nature News, Nature Publishing Group, www.nature.com/scitable/topicpage/the-origin-of-mitochondria-14232356.

9. “What Is the Human Genome Project?” NHGRI, www.genome.gov/human-genome-project/What.

10. Pertea, Mihaela, and Steven L Salzberg. “Between a Chicken and a Grape: Estimating the Number of Human Genes.” Genome Biology 11.5 (2010): 206. PMC. Web. 7 Feb. 2018.