Prologue to the Kingdom of Genes: What is genetic material?

Produced by: Science Popularization China

Author: Li Lei

Producer: China Science Expo

Today, genes have become a common knowledge among everyone. Whether it is nucleic acid, paternity testing, or professional magazines, they have always been paying attention to genes.

For example, in 2022, Science magazine published six articles at the same time and introduced the latest results of the Human Genome Project on its cover, calling it a new milestone in the Human Genome Project.

Science Magazine Cover

(Image source: Science official website)

What is a genome? How is it related to genes? Why do top journals still devote so much space to genes? What is the significance of genes to us? We will use five articles to tell you the story of the genetic kingdom.

Before introducing the genome, we must understand genes.

Today, gene is a very familiar word to the general public, and people of all ages know this word. However, many people may not know that the word gene is actually a new word, and it has only been around for more than a hundred years.

Let’s start from the very beginning.

A long exploration—what is genetic material?

What influences the characteristics of people and various life forms is an eternal topic. Humans have been thinking about this question for a long time and have made some guesses, such as the Eastern legend of Nuwa creating people out of clay, and the Western Pythagoras's theory that earth, air, water, and fire make up life. These guesses often differ due to cultural and historical differences.

However, there is a phenomenon that allows people to have some more essential guesses about the factors affecting this trait, that is, similarity , especially the similarity between blood families. This suggests that these determinants are closely related to kinship.

This gave birth to another important word - heredity .

Compared with other unpredictable factors, the variables of heredity are much smaller, mainly parents and children. Therefore, there are many simple cognitions about the nature of heredity, such as folk sayings such as "Dragons give birth to dragons, phoenixes give birth to phoenixes", which means that there are common genetic factors between parents and offspring, and these factors should be rooted in the body.

Following this line of thought, people began to look for what substance in organisms is responsible for heredity.

Of course, this road is very long. As early as the time of Pythagoras, he proposed the theory of heredity. He believed that heredity should come from semen, which circulates throughout the body to obtain various information and then passes it on to the next generation. Later, people gradually realized that both parents should be involved in the matter of heredity, but what exactly are these factors?

For example, Darwin, a well-known biologist, proposed a hypothesis that various cells of organisms have specific reproductive particles, called "microbuds" or "pansons", which are passed on during reproduction. Of course, there are other speculations, such as blood as a genetic factor.

However, there are always some great people who can transcend the times and come up with refreshing theories, a typical example being Mendel . Without knowing what genetic material is, he creatively proposed that "genetic factors" exist in organisms, and proposed Mendel's laws of inheritance - the law of gene segregation and the law of independent assortment - through statistical methods.

This law was not proven to be correct until decades later, and it still amazes people today.

Several decades after Mendel's death, Danish geneticist Johnson formally proposed the word "gene" for the first time. Gene comes from Greek, meaning "life". It can be seen that this word has been related to reproductive inheritance from the beginning. As a worker in the field of life sciences, I think the Chinese translation of the word "gene" is a model of faithfulness, expressiveness and elegance, achieving harmony between transliteration and literal translation.

Gene

(Image source: wiki, translated by the author)

However, the concept of genes at that time is actually quite different from that of genes today. But since then, humans have at least reached a consensus that there is a part of the body that is responsible for transmitting genetic information, that is, genetic material.

So, what is the nature of genetic material? Scientists have been exploring for decades. Of course, the road was not smooth, and it took countless scientists a lot of effort. It was not until the last century that the development of life sciences, especially biochemistry and genetics, finally allowed us to determine the nature of genetic material. Among them, three experiments played a key role.

Three ingenious experiments reveal that the essence of genetic material is nucleic acid

To study the properties of genetic material, we first need to find some relatively simple models to reduce the difficulty of the experiment as much as possible. At this time, viruses and bacteria with relatively simple structures have become the research objects.

Compared to the vast majority of eukaryotic organisms represented by humans, the structures of viruses and bacteria are much simpler. Take DNA as an example. In viruses and bacteria, DNA often exists independently, while in eukaryotic organisms, DNA is wrapped by many proteins such as histones to form chromatin (meaning an object that can be dyed), which contains both DNA and proteins, as well as structures such as the centromere in the middle and the telomeres at both ends, which is very complex.

Of course, when we review these experiments, we still have to pretend that we don’t know what the nature of genetic material is, so that we can appreciate the subtleties of these three famous experiments.

However, it is not that we are completely ignorant. At least in the early stages of exploring the nature of genetic material, researchers have generally locked down the scope of genetic material, which is nucleic acid or protein. This is because through biochemical methods, it can be determined that the core structures of extremely simple life forms such as viruses are only two types, namely nucleic acid and protein.

Everyone is familiar with these two. Nucleic acid was discovered by Michel in white blood cells in 1869, and it was named nuclide at that time. Later, Altmann found that this molecule was acidic, so it was called nucleic acid. Protein was discovered even earlier, in 1838 by scientist Mulder.

After making this basic judgment, the next step is to distinguish which one is the genetic material, nucleic acid or protein, or whether they are both?

1. The classic transformation experiment proved that DNA is the genetic material

This experiment was conducted successively by Griffith and Avery. The so-called transformation is to transform one type of pneumococcus into another type.

First, we need to introduce the two types of pneumococci. One is the toxic S-type pneumococcus (smooth) with a smooth surface and a capsule, and the other is the non-toxic R-type pneumococcus (rough) with a rough surface and no capsule. They can be distinguished directly from the appearance.

Griffith then conducted four sets of experiments.

In the first group, mice were injected with live R-type bacteria and did not die.

The second group was injected with live S-type bacteria, and the mice died, and live S-type bacteria were found in the mice's bodies.

The third group of mice were injected with heat-killed S-type bacteria, but they did not die.

The fourth group was injected with live R-type bacteria and heat-killed S-type bacteria. The mice died and live S-type bacteria were found in their bodies.

Griffith's four experiments

(Image source: wiki, translated by the author)

Through a simple comparison, we can see that groups 1 and 2 of experiments proved the activity of the R and S types themselves, experiment 3 proved that the S type can be killed, and experiment 4 proved that a certain substance in the toxic S-type dead bacteria can be transferred to the non-toxic R-type live bacteria and make them toxic.

However, with the technology at the time, it was impossible to distinguish the chemical composition of this "conversion factor" and what it was, so the Avery experiment came about.

Avery was lucky because at that time humans had already distinguished components such as DNA, protein and polysaccharides from bacteria. So Avery added these components to the heat-killed S-type bacteria. It was found that only the addition of DNA could make the bacteria regain their infectivity.

This experiment also confirmed for the first time that DNA was the transforming factor.

With this experiment, the next experiment is a natural progression, that is, does DNA, as a conversion factor, contain partial genetic information or all genetic information?

This time, Hershey and Chase worked with simpler bacteriophages.

2. DNA contains all genetic information—evidence from bacteriophages

As the name suggests, bacteriophage is an organism that can invade bacteria. It is a virus with a simpler structure than bacteria. It mainly consists of two parts: a protein capsid on the outside and DNA inside.

Since proteins and DNA have different chemical element compositions, for example, proteins contain S (sulfur), while DNA basically does not contain S. On the contrary, P (phosphorus) mainly exists in DNA. Therefore, proteins and DNA can be labeled by radioactive isotope technology, so that they can be distinguished.

Next, they used radioactive isotope-labeled phages to infect bacteria and found that during the infection process, proteins did not enter the host bacteria, only DNA did. The entered DNA could further guide the bacteria to synthesize a complete phage. The capsid protein of this newly synthesized phage did not contain the isotope-labeled S element.

This not only further proves that DNA is the genetic material rather than protein, but also proves that DNA contains all the genetic information.

Related experiments

(Image source: wiki)

3. Tobacco mosaic virus infection proves that RNA can also be used as genetic material

With the above experiments, people began to think about another question: there are two types of nucleic acids. DNA is deoxyribonucleic acid, so is RNA, which is not deoxygenated, genetic material? So there was the Conradt experiment.

Conrath chose the tobacco mosaic virus containing only RNA to infect tobacco, and found that the virus containing only RNA could also infect and replicate, which confirmed that RNA is also genetic material.

Conrad's experiment

(Image source: Reference 1)

At this point, the controversy over genetic material has basically come to an end, and scientists now have a basic consensus that nucleic acids are genetic material.

Now that we know that genetic material is nucleic acid, what are genes?

The next article will tell you.

Editor of this article: Sun Chenyu

References:

1.Russell,P., I Genetics, a molecula approach, 3rd edition, 2009, edited by Yue-Wen Wang. Pearsons,USA