discussion DNA versus RNA
Scientists are thinking that the life on Earth appeared about 3.7 – 3.5 billion of years ago . The first life forms were very primitive single cell organisms. They established the molecular mechanisms to synthesize organic molecules that we are observing today common to all living organisms . One of the characteristics of life is that all living things have DNA as a carrier of genetic information . However, the scientists think that this was not always the case, the life begin using RNA as a genetic material and later switched to DNA .
What do you think, why this could be? Which processes that promotes preserving the genetic information and at the same time allowing for Genetic variation were made possible when Nature started to use DNA instead of RNA? Why it is so difficult, if not impossible, to acquire immunity against RNA viruses? Does it have something to do with the different nature of the viruses, or with the higher mutation rates in the RNA world?
1. Early Life on Earth – Animal Origins
2. The Universal Features of Cells on Earth
3. RNA was the first genetic molecule.
There are many RNA viruses like Ebola, SARS, HIV, but the one we are most familiar with, of course, is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID19) . As of June 14th, the death toll was 600 thousand in the US and 30.1 million worldwide . In order to understand why it is so difficult to acquire immunity against RNA viruses, we must first understand the origins of RNA.
Currently, all living species have DNA as a carrier of genetic information, but scientists contemplate that RNA came first then evolved into DNA; a hypothesis known as ‘RNA World Hypothesis’ [3,4]. Many speculate pre-RNA molecules carried genetic information and had catalytic and structural functions which evolved into RNA . The RNA enzyme, ‘ribozyme,’ copied RNA molecules and evolved into the ribosome. This would mean that protein enzymes existed before DNA and the RNA polymerase in this ‘RNA World’, with lack of proofreading indefinitely replicated. These replicated RNAs would have undergone survival of the fittest leading to single stranded DNA then eventually to double stranded DNA . The chemical differences between RNA and DNA give clues to this hypothesis. Ribose, found in RNA can be created from formaldehyde (HCHO) which existed on primitive earth whereas deoxyribose, found in DNA, is produced from ribose–signifying that ribose came before deoxyribose . By doubling RNA and using deoxyribose instead of ribose, DNA became more stable and took the role of passing on genetic information . This hypothesis is useful in explaining varying immunity to different viruses.
Viruses contain either RNA or DNA genome surrounded by a virus-coded protein shell . RNA viruses make up 70% of all viruses and have a higher mutation rate than DNA viruses due to RNA replication being more susceptible to error than DNA . The lack of proofreading by RNA polymerase in RNA viruses accounts for one mistake for every 10^-4 nucleotides copied into RNA, this leads to continuous generation of new variants which are more adaptable to new hosts . Whereas DNA has DNA polymerase which has proofreading abilities and therefore does not mutate as rapidly . This explains why immunity against RNA viruses is more difficult to attain–they are constantly evolving and becoming more resistant.
RNA polymerase and its inability to proofread made way for the evolution of DNA, but it also allows for rapid mutation and short replication times . After researching for this discussion post, I can’t help but think this is all paradoxical. It seems that the hypothesized mechanisms which gave rise to the evolution of RNA to DNA, and thus current day life as we know it, may also be the reason why 30.1 million people have died due to the RNA virus, COVID19.
I believe that the first life forms used RNA as a genetic material instead of DNA because it is a simpler molecule. RNA is one strand, compared to DNA which is two strands, allowing for less energy and “cellular machinery” to be used to copy new genetic material. Additionally, RNA mutates at a rate a million times greater than DNA (Duffy). More mutations lead to more genetic variation and more variation increases the species chance of survival. Especially considering that during this time period, the earth’s environment was known as primordial soup, containing hot gaseous and liquid elements, thus making it difficult for any species to survive.
When DNA started to be used instead of RNA, it allowed for more consistent gene replication because a mutation would have to occur in both strands of DNA, and the emergence of mismatch repair proteins (MMR). Because of this, fewer mutations that would eventually be expressed occurred. This is both a beneficial and harmful thing. It is beneficial because the mutations that are being avoided could be deadly. However, it could be harmful because it decreases genetic diversity in the population.
As mentioned previously, the mutation rate in RNA, and thus RNA viruses, is incredibly high. Thus, it is difficult to acquire immunity against these viruses because they are changing so rapidly. You could become immune to one specific variant of an RNA virus, but it could quickly evolve into another strain that you are not immune to. This is precisely what is happening with the ongoing COVID-19 pandemic. Those vaccinated are not fully immune to the relatively recently identified B1351 variant and still can experience symptoms (Bollinger).
First, let’s talk about the three major chemical differences between RNA and DNA. RNA has a hydroxyl group on it’s 2’ carbon of the sugar molecule, while DNA lacks the hydroxyl group and just has a hydrogen. Thus, RNA is called ribonucleic acid and DNA is called deoxyribonucleic acid. In addition, DNA and RNA have the same bases except one. RNA contains uracil instead of thymine. Lastly, DNA is large and double stranded but RNA is most often single-stranded and has less nucleotides. These differences lead DNA to be much more stable than RNA (Hartwell, 2018). Higher stability can explain why there was a switch from RNA as the genetic material to DNA.
Since DNA has a second, complementary strand, it allows for redundancy. This means that either strand of the double helix can code the sequence of the opposite strand. This helps provide a way to check and repair errors that may arise. In addition to this, DNA polymerase I and III have proofreading ability which helps maintain low mutation rates during DNA replication (Hartwell, 2018). Contrastingly, RNA polymerases lack a proofreading ability and this leads to a high rate of mutations. If the RNA polymerases make mistakes, they don’t have the ability to correct them and the mutations remain in the newly synthesized strand (Concept 26 RNA was the first genetic molecule). Although mutations in DNA are relatively rare, they still occur. Mutations, along with independent assortment and crossing over during meiosis, lead to genetic variation when using DNA.
The high mutation rate and rapid replication of RNA viruses is a main reason why it is extremely difficult to have immunity against RNA viruses. There is most likely variation between the progeny viruses and therefore immunity against one may not mean immunity against another