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Evolution of viruses

Virus evolution and genetic variation. Drug-resistant HIV. Reassortment of flu viruses.

Key points:

  • Viruses undergo evolution and natural selection, just like cell-based life, and most of them evolve rapidly.
  • When two viruses infect a cell at the same time, they may swap genetic material to make new, "mixed" viruses with unique properties. For example, flu strains can arise this way.
  • RNA viruses have high mutation rates that allow especially fast evolution. An example is the evolution of drug resistance in HIV.


Have you ever wondered why a different strain of flu virus comes around every year? Or how HIV, the virus that causes AIDS, can become drug-resistant?
The short answer to these questions is that viruses evolve. That is, the "gene pool" of a virus population can change over time. In some cases, the viruses in a population—such as all the flu viruses in a geographical region, or all the different HIV particles in a patient's body—may evolve by natural selection. Heritable traits that help a virus reproduce (such as high infectivity for influenza, or drug resistance for HIV) will tend to get more and more common in the virus population over time.
Not only do viruses evolve, but they also tend to evolve faster than their hosts, such as humans. That makes virus evolution an important topic—not just for biologists who study viruses, but also for doctors, nurses, and public health workers, as well as anyone who might be exposed to a virus. (Hint: that means all of us!)

Variation in viruses

Natural selection can only happen when it has the right starting material: genetic variation. Genetic variation means there are some genetic (heritable) differences in a population. In viruses, variation comes from two main sources1:
  • Recombination: viruses swap chunks of genetic material (DNA or RNA).
  • Random mutation: a change occurs in the DNA or RNA sequence of a virus.
    We can see variation and evolution of viruses all around us if we know where to look—for instance, in the new flu strains that appear each year.

Mixing it up: Recombination

Before we look specifically at the flu, let's examine how viruses swap DNA and RNA in a process called recombination.
Recombination usually happens when two viruses have infected the same cell at the same time. Since both viruses are using the cell to crank out more virus particles, there will be lots of virus parts – including newly made genomes – floating around in the cell at once.
Reassortment between two viral strains that infect the same cell.
Strain A has eight segments of genetic material. Strain B also has eight segments, which bear similar genes but in different versions.
Both strains co-infect the same host cell. The segments get mixed up in the host cell.
This results in the production of a reassortant virus. The reassortant virus has segments 3, 6, 7, and 8 from strain A and segments 1, 2, 4, and 5 from strain B.
Image credit: "Segment reassortment," by ViralZone/Swiss Institute of Bioinformatics, CC BY-NC 4.0.
Under these circumstances, recombination can happen in two different ways. First, similar regions of viral genomes can pair up and exchange pieces, physically breaking and re-connecting the DNA or RNA. Second, viruses with different segments (kind of like tiny chromosomes) can swap some of those segments, a process called reassortment. 2,3

Recombination and influenza ("the flu")

Influenza ("flu") viruses are masters of reassortment. They have eight RNA segments, each carrying one or a few genes.4
When two influenza viruses infect the same cell at the same time, some of the new viruses made inside of the cell may have a mix of segments (e.g., segments 1-4 from strain A and segments 5-8 from strain B).
Human influenza virus and bird influenza virus infect same pig cell. Each has eight segments of RNA in its genome.
The segments get mixed up as new viruses are made in the cell.
Various different combinations could be made. For example, we could get one virus particle with segments 1-4 from the human virus and segments 5-8 from the other, and vice versa.
Pigs in particular are well-known "mixing vessels" for influenza viruses.5 Pig cells can be recognized, and thus infected, by both human and bird influenza viruses (as well as pig viruses).6 If a cell in the pig is infected with two types of virus at the same time, it may release new viruses that contain a mixture of genetic material from the human and bird viruses.
This kind of swap is common for influenza viruses in nature. For example, remember the H1N1 influenza strain ("swine flu") that caused a pandemic in 2009? H1N1 had RNA segment from human and bird viruses, as well as pig viruses from both North America and Asia. This combo reflects a series of reassortments that occurred step by step over many years to produce this H1N1 strain.5,7

Viral mutations

We've seen how recombination can affect virus evolution, but what about mutation? A mutation is a permanent change in the genetic material (DNA or RNA) of a virus. A mutation can happen if there is a mistake during copying of the DNA or RNA of the virus.
Some viruses have very high mutation rates, but this is not universally the case. In general, RNA viruses tend to have high mutation rates, while DNA viruses tend to have low mutation rates.8
Why is this the case? The key difference lies in the copying machinery. Most DNA viruses copy their genetic material using enzymes from the host cell, called DNA polymerases, which “proofread" (catch and fix mistakes as they go). RNA viruses instead use enzymes called RNA polymerases, which don't proofread and thus make many more mistakes.9

Case study: HIV drug resistance

Human immunodeficiency virus (HIV) is the virus that causes acquired immune deficiency syndrome (AIDS). HIV is an RNA virus with a high mutation rate and evolves rapidly, leading to the emergence of drug-resistant strains.

HIV's high mutation rate

Because RNA viruses like HIV have a high mutation rate, there will be lots of genetic variation in the population of HIV viruses in a patient's body. Many of the mutations will be harmful, and the mutant viruses will simply "die" (fail to reproduce). However, some mutations help viruses reproduce under specific conditions. For instance, a mutation may provide resistance to a drug.10

Evolution of drug resistance in HIV

Certain drugs can block the replication of HIV by inhibiting key viral enzymes. Taking one of these drugs will at first reduce a patient's viral levels. After awhile, however, the HIV viruses typically "bounce back" and return to high levels, even though the drug is still present. In other words, a drug-resistant form of the virus emerges.10
To see why this took place, let's use the example of a specific type of antiviral drug, a reverse transcriptase inhibitor. Reverse transcriptase inhibitors, like the nevirapine molecule shown in the diagram below, bind to a viral enzyme called reverse transcriptase (the red-and-brown structure). The drug keeps the enzyme from doing its job of copying the RNA genome of HIV into DNA. If this enzyme is inactive, an HIV virus can't permanently infect a cell.11
Ball-and-stick molecular model of HIV reverse transcriptase enzyme with the reverse transcriptase molecule nevirapine bound to it.
Image modified from "Exploring the structure," by David S. Goodsell, RCSB PDB Molecule of the Month, CC BY 4.0.
Most HIV viruses are stopped by nevirapine. However, a very small fraction of the viruses in the HIV population will (by random chance) have a mutation in the gene for reverse transcriptase that makes them resistant to the drug. For instance, they might have a genetic change that alters the drug's binding site on the enzyme, so that the drug is no longer able to latch on and inhibit enzyme activity.
The viruses with this resistance mutation will reproduce despite the presence of the drug and, over generations, can re-establish the viral levels present before the drug was administered. Not only that, but the entire virus population will now be resistant to the drug!

HAART drug resistance

If HIV can evolve its way around a drug, how can the virus be stopped? What seems to work best is a combination approach, with three or more drugs taken at the same time. This approach to treatment is called highly active antiretroviral therapy, or HAART for short. The drugs given in a HAART "cocktail" typically target different parts of the HIV lifecycle.12,13
The HAART approach works because it's relatively unlikely that any one HIV virus in a population will happen to have three mutations that give resistance to all three drugs at the same time. Although multi-drug-resistant forms of the virus do eventually evolve, multi-drug combinations considerably slow the evolution of resistance.10
To learn more about the biology of HIV, please see the article on virus lifecycles. To learn more about symptoms, treatment, and prevention of HIV and AIDS, please see the Health & Medicine section on HIV and AIDS.

Why do viruses evolve so fast?

Viruses evolve faster than humans. Why is this the case?
As we saw in the case of HIV, some viruses have a high mutation rate, which helps them evolve quickly by providing more variation as starting material. Two other factors that contribute to the fast evolution of viruses are large population size and rapid lifecycle.14
The bigger the population, the higher the odds that it'll have a virus with a particular random mutation (e.g., one for drug resistance or high infectivity) on which natural selection can act. Also, viruses reproduce quickly, so their populations evolve on shorter timescales than those of their hosts. For instance, the HIV virus goes through its lifecycle in just 52 hours, as compared to roughly 20 years for the human lifecycle!15
What tools do we have to combat fast-evolving viruses? Taking steps to prevent transmission, identifying new drugs for treatment, and developing and using vaccines are all important strategies.

Want to join the conversation?

  • winston baby style avatar for user jesusgomez.JG119
    I know this will most likely be impossible but is it possible for a virus to evolve rapidly enough to spread and wipe out life on earth, I mean the H1N1 pandemic looked bad enough right?
    (12 votes)
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    • starky ultimate style avatar for user ++§ Αλεκσανδαρ
      Viruses could never wipe out life on Earth. There are two reasons for that.

      1) The more successful the host is, the more successful is the virus going to be. Humans are very widespread specie, which means that viruses that attack us have very good chances of spreading from one victim to another. But, as the population of their hosts declines, viruses will have more trouble in spreading. In the end, when there would be only a few isolated groups of people left, our imaginary deadly virus wouldn't be able to spread anymore.

      2) Someone will be immune to virus. Those people will survive and continue the humanity. Their children will have their genes and they will all be immune to that specific virus. Spanish flu couldn't affect everyone, HIV can't affect everyone, none virus can affect everyone. It's just how things work.
      (32 votes)
  • duskpin ultimate style avatar for user Novalis Proximus
    If the HIV virus only has a lifespan of 52 hours, then wouldn't the HAART "cocktail" therapy be able to block the HIV virus for at least 52 hours, thus causing the death of the virus? Unless the HIV virus evolves and mutates within those 52 hours, which I highly doubt is always and/or mostly the case.
    (4 votes)
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  • leaf green style avatar for user meghanmilstead
    What does rna mean?
    (1 vote)
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  • blobby green style avatar for user Logan Bennett
    What would happen if 3 viruses combined?
    (2 votes)
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  • area 52 blue style avatar for user Alexander Liu
    Can a virus wipe out the dinosaurs or cause a mass extinction event?
    (2 votes)
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    • starky ultimate style avatar for user ++§ Αλεκσανδαρ
      I know there will be people who disagree with me, but i firmly believe the answer to both questions is no.

      (Just as a side note, dinosaurs aren't extinct. Present-day birds are indeed dinosaurs.)

      To cause a mass extinction, a virus would have to be able to infect a broad variety of species and cause disease with a mortality rate of 100 %. To my knowledge, no known type of viral disease has such a high mortality rate (even though some are close to that number!). The more lethal a virus is, the sooner it will run out of possible hosts. Earlier types of ebola virus were very lethal (the highest recorded mortality rate was 90 % during the 2003 epidemic in DR Congo), but those viruses didn't cause massive epidemics. Each outbreak had several hundreds of casualties.

      Some scientists speculate that viruses could have caused several smaller extinctions in the history of life on Earth. Fossil records confirm that in between so-called mass extinctions, there were also smaller extinction events which happened during periods of relatively stable environmental conditions. So what was the cause? Even though some believe it was because of the viruses, as of now we have no evidence to support that claim.

      That's just my opinion. The topic is still very controversial, and i would be interested to hear others' opinions.
      (4 votes)
  • duskpin ultimate style avatar for user katlee25
    how does the virus affect human population?
    (3 votes)
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  • leaf red style avatar for user marchgeffar
    How does the influenza virus affect the human body?
    (2 votes)
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    • duskpin ultimate style avatar for user Arki🖤
      Influenza virus has two different glycoproteins on it's lipid envelope called neuraminidase (helps the virus to leave the host cell)and haemaglutinin(aids the virus to enter the host cell).

      In humans,haemaglutinin binds to (saliac acid) receptors on the epithelial cells in the upper respiratory tract and then the virus enters the cell through a process called 'endocytosis'.
      Once in the cell , the negative sense Rna is replicated into positive sense ss rna which then helps in the process of progeny production.
      Now viruses mutate very rapidly...Therefore the daughter viruses have slightly different glycoproteins than their parent and other progeny viruses.
      This is why you can get flu every year or even twice or more in a year.

      Now, neuraminidase is a receptor destroying protein which is why it aids the virus to elude from the cell by destroying saliac acid receptors.
      (5 votes)
  • blobby green style avatar for user jademill14
    Vaccines provoke the host's immune system to produce appropriate antibodies against the antigen in the vaccine. In relation to the section, Case study: HIV, why do vaccines for viral infections/viruses become ineffective over time? Is it because as viruses mutate, antigens develop on their surfaces which are different to the original antigens on the virus before mutation, and hence require the production of different antibodies to be granted immunity against the new, mutated virus?
    (3 votes)
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  • blobby green style avatar for user Lia F
    Do viruses require energy for metabolism?
    (2 votes)
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  • boggle blue style avatar for user 𝚡.𝚊𝚜𝚙𝚎𝚛
    Why is it that the article says that the average human cycle is only 20 years?
    (2 votes)
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