Solving problems with phylogenetic trees

by Dr. Joel Cracraft

Phylogenetic trees are predictive tools. They represent the expectation that close relatives share characteristics not found in more distant relatives. If we plot similarities and differences on a tree, we have a hypothesis of how these characters changed across evolutionary time. Understanding this change—whether in anatomical, behavioral, or molecular characters—has many applications.

Trees are also useful identification tools. Typically, when an organism is discovered, scientists compare its features with those of specimens in collections to identify whether it is already known or it is a new species. For example, because it's quick and easy to obtain genetic data on viruses, bacteria, and other microbes and compare them to large sequence databases such as GenBank, scientists routinely use these comparisons to identify microbes. As a consequence, the health sciences, forensics, and bioprospecting industries all rely on phylogenetic sequence analysis. The following are several examples of this powerful approach at work.

In the summer of 1999 a small number of elderly residents of Queens, New York, were fatally stricken by an infection that doctors initially diagnosed as St. Louis encephalitis, a mosquito-borne virus. At the same time, wild crows began to die in startling numbers, along with captive birds in New York-area zoos. The two events were linked when phylogenetic analysis of the viral sequences revealed a new strain of West Nile virus, a mosquito-borne disease rarely seen outside Africa, the Middle East, and Europe. The virus circulates between birds and mosquitoes but can be transmitted to humans and other mammals. Since it emerged in New York, West Nile has spread to every state, killing small numbers of people and causing major bird mortality. Phylogenetic analysis proved invaluable in understanding the timing and direction of spread of this disease and in providing health officials with knowledge that has lessened its impact. Today, in the United States, the West Nile virus is the most common disease transmitted by mosquitoes, one of the more consequential examples of how invasive species can affect human health.

Phylogenetic analysis also helped scientists understand SARS-CoV-2, the virus behind the COVID-19 pandemic that killed nearly 7 million people in its first four years. Analyzing samples from people and animals, they found that SARS-CoV-2 was closely related to a viral sequence from a bat host. They also looked at SARS-CoV-1 and MERS-CoV-2, viruses related to SARS-CoV-2. These were responsible for SARS and MERS, infectious diseases that emerged as threats in the first two decades of the 21st century but were contained more readily than COVID-19. Both SARS and MERS were zoonotic—that is they jumped from the wild to humans. SARS-CoV-1 jumped from civets and MERS-CoV-2 from camels. As scientists can see from studying phylogenetic trees, SARS-CoV-2, MERS-CoV-2 and SARS-CoV-1 all have closely related viral sequences from bat hosts.

Earth's ecosystems abound with microbial life, but since most of those microbes cannot be cultured in a lab environment, identifying and studying them is extremely difficult. However, the tool of metagenomics—the study of DNA extracted from environmental samples like soils or water—offers great promise for increasing life's inventory. Metagenomic samples contain the DNA of thousands of organisms, mostly forms of bacteria. Comparing their gene sequences to those of known organisms using phylogenetic analysis often reveals new life forms.

Many of these new species are potential sources of bioproducts. Perhaps the best example is a bacterium called Thermus aquaticus that was discovered in the thermal hot springs of Yellowstone National Park. As its name implies, it lives in near-boiling waters, which is possible because its DNA polymerase, an enzyme that helps DNA to replicate, functions at very high temperatures. Scientists developed a process called polymerase chain reaction (PCR) that uses this enzyme to make millions of copies of a DNA strand (a process that requires heating the DNA) so that it can be sequenced easily. This single technology has enabled a revolution in the biomedical and genome sciences, including evolutionary biology, and has saved countless lives through diagnostic tests and vaccine development and production.

This discovery is just the tip of the iceberg. Applying phylogenetics and the principles of molecular evolution to the search for new life is leading to numerous other discoveries with important applications across the life sciences.