Molecular evolution is used to study and combat diseases

Many of the most problematic human diseases are caused by living, evolving organisms that present a moving target for modern medicine. Recall the example of influenza described in the opening story of this chapter and that of HIV in Chapter 21. The control of these and many other human diseases depends on techniques that can track the evolution of pathogenic organisms over time.

The transportation advances of the past century have allowed humans to move around the world with unprecedented speed and frequency. Unfortunately, this mobility has allowed pathogens to be transmitted among human populations, and between humans and other animals, at increasing rates. Cross-species transmission of viruses has led to the global emergence of many “new” diseases.

In the opening of this chapter, we described the devastating influenza pandemic of 1918–1919. Michael Worobey and his colleagues used evolutionary analyses of influenza genomes to explore the reasons why this particular flu epidemic was so much more severe than any before or since (Investigating Life: Why Was the 1918–1919 Influenza Pandemic So Severe?). They reconstructed the evolutionary history of influenza viruses in birds, pigs, horses, and humans and found that influenza viruses have repeatedly been transferred from birds to the various mammals. Most cross-species transfers have been accompanied by a major epidemic in the new host. The 1918–1919 epidemic occurred immediately after such a transfer between hosts. Human immune systems had no experience with the newly acquired virus, and the strong resulting reaction caused many of the strongest symptoms and deaths. Now that cross-species transmission has been associated with major flu epidemics, health workers around the world are constantly monitoring flu cases for indications of new cross-species transmissions. When emerging viruses are identified early on, efforts to control and irradicate them have a good chance of being successful. So far, our understanding of molecular evolution has prevented a repeat of the devastating flu pandemic of 1918–1919.

Studies of the genomes of many infectious agents have advanced our understanding and treatment of the diseases they cause. For example, rodent-borne hantaviruses were identified as the source of widespread respiratory illnesses, and the virus (and its host) that causes Sudden Acute Respiratory Syndrome (SARS) was identified using evolutionary comparisons of genes. Studies of the origins, the timing of emergence, and the global diversity of many human pathogens depend on the principles of molecular evolution, as do the efforts to develop and use effective vaccines against these pathogens. For example, the techniques used to develop modern polio vaccines, as well as the methods used to track their effectiveness in human populations, rely on molecular evolutionary approaches.

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investigating life

Why Was the 1918–1919 Influenza Pandemic So Severe?

experiment

Original Papers: Tumpey, T. M. et al. 2005. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science 310: 77–80.

Worobey, M., G.-Z. Han, and A. Rambaut. 2014. A synchronized global sweep of the internal genes of modern avian influenza virus. Nature 508: 254–257.

As conveyed in the story that opens this chapter, the 1918–1919 influenza pandemic killed more than 50 million people worldwide—many more than the number of World War I–related combat deaths. Unlike flu epidemics before or since, the flu viruses that circulated in the 1918–1919 epidemic triggered an especially intense reaction in the human immune system. What was different about the flu viruses circulating at that time?

Terrence Tumpey and his colleagues at the Centers for Disease Control and Prevention isolated and sequenced a complete flu virus from biopsies of 1918 victims of the pandemic. Michael Worobey of the University of Arizona and his colleagues then analyzed and compared the genomes of flu viruses that have been collected from 1918 to the present, from birds, pigs, horses, and humans. The viruses are largely transmitted within each of these host groups, but rarely jump between host groups. Worobey and his colleagues reconstructed the phylogeny of the viruses to determine if the 1918 virus had recently “jumped” into human populations from another species.

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work with the data

Original Paper: Worobey, M., G.-Z. Han and A. Rambaut. 2014.

Michael Worobey and his colleagues were able to reconstruct many of the cross-species transmissions of influenza virus that have occurred over the past 150 years, and to determine a likely reason that the 1918–1919 pandemic in humans was so severe. Can you replicate their conclusions?

QUESTIONS

Question 1

All the influenza viruses shown in the tree in the experiment are thought to have arisen in one group of host animals. Which group of animals do you think is the original source of the virus, and why?

Birds appear to be the original source of influenza viruses that now cause flu in the various mammal species (horses, pigs, and humans). The bird lineages extend to the base of the tree, and appear to be closely related to each lineage of influenza virus that occurs in a mammal.

Question 2

How many cross-species transmissions are shown on the tree? What hosts were involved (as source and recipient) of each transmission event?

The tree shows five cross-species transmissions: two from birds to horses, two from birds to pigs, and one from birds to humans. The human flu viruses are most closely related to viruses in pigs (hence the common name “swine flu”), and it is possible that the virus was transferred from birds to pigs and then from pigs to humans in a short period of time late in the second decade of the 1900s.

Question 3

What do you think is a likely explanation for the severity of the 1918–1919 influenza pandemic in humans?

In 1918, a new strain of influenza had just entered human populations (as well as pig populations). Humans' immune systems would not have had any prior experience with this new strain of influenza, and so would not have been prepared for an effective defense.

Question 4

Influenza was known in humans well before the 1918–1919 pandemic. Why do you think that no human influenza viruses are indicated on the tree before about 1918?

Earlier flu cases were likely caused by other cross-species transfers of different strains of influenza into human populations. Those flu strains appear to have been eliminated from human populations, and so were not available for sampling in this study (and therefore do not appear on the tree).

A similar work with the data exercise may be assigned in LaunchPad.

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In the future, molecular evolution will become even more critical to the identification of human (and other) diseases. Once biologists have collected data on the genomes of enough organisms, it will be possible to identify an infection by sequencing a portion of the infecting organism’s genome and comparing this sequence with other sequences on an evolutionary tree. At present it is difficult to identify many common viral infections (those that cause “colds,” for instance). As genomic databases and evolutionary trees increase, however, automated methods of sequencing and rapid phylogenetic comparison of the sequences will allow us to identify and treat a much wider array of human illnesses.