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Why should anyone care about phylogeny?

- One of the best tools for understanding the spread of contagious disease

Uses of phylogenies: Medicine

• Learn about the origin ofdiseases

• Look for diseaseresistance mechanismsin other hosts to identifytreatment and therapy inhumans

Multiple origins of HIV from SIV(Simian Immunodeficiency Virus)

Example of disease phylogeny

Source of Severe Acute Respiratory Syndrome coronavirus wasunknown… phylogenetic analyses traced it to civets and bats.

USINGPHYLOGENY TO

SOLVE A HEALTHMYSTERY

In 1990, a womanwith no HIV riskfactors contractedHIV. The hypothesiswas put forward thatshe contracted it fromher HIV positivedentist.

A phylogenetic tree ofHIV sequences fromthe dentist, sevenpatients, and severallocal controls clearlyshows that 5 of thepatients had HIV virussequences closest tothose of the dentist.

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- One of the best tools for understanding the adaptive evolution of viralpathogens (aids vaccine design)

Beating Flu with Evolutionary Biology

Human Flu Viruses (Influenza A and B)cause frequent flu epidemics

Flu viruses evolve very rapidly; this iswhy there is a new flu vaccine each year

The body protects itself against flu byproducing antibodies to hemagglutininon the flu virus protein coat

One might hypothesize that flu viruseswith novel hemagglutinins would befavored under natural selection

In the late 90’s, WalterFitch, Robin Bush, andco-workers produced aphylogeny of flu virusesover more than 10 yearsusing DNA from frozenviral samples.The resultingphylogenetic tree showeda non-random pattern ofwhich flu strain from eachyear would become thedominant strain in thenext year.Indeed, they found thatstrains with amino acidchanges at hemagglutininsites tended to become thedominant strain next year.This has since beenhelpful in selecting fluvaccines




- Phylogeny provides a “road map” that can lead you to previously unknownbiological sources of valuable chemical compounds (e.g. pharmaceuticals)

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Plant secondary chemicals have proven to be a vast reservoir foruseful pharmaceuticals — these include analgesics, diuretics, laxatives, tranquilizers, contraceptive agents, and cough drops.

Clinically proven drugs derived from higher plants include morphine, codeine, atropine, quinine, digitalis, and many others.

Scientists have only examined about 1 percent of existing plant speciesfor such useful pharmaceuticals.

The powerful anti-cancer drug Paclitaxel (Taxol) caused asensation when it was discovered in the bark of Pacific YewTrees, Taxus brevifolia.

However, almost 100,000 pounds of bark were needed forclinical trials alone, and bark collection kills the tree. It wasestimated that if Paclitaxel were used regularly to treatmelanomas and ovarian cancer in the U.S., 360,000 treeswould have to be destroyed each year. (!!!!!)

In the 90’s, phylogenetic studies of yew trees guided scientiststo other species of Taxus that could be used as sources fortaxol (including Taxus baccata)

Now Taxus genes in transformed bacterial genomes producepaclitaxel at large scales

Currently, spider,snake, and fishphylogenies arebeing used in asurvey to search formedically valuablecompounds in thevenoms of theseanimals.

Powerful anticancerand antistrokedrugs have alreadybeen isolated fromvenoms of snakes





- In gene and protein research, phylogeny allows one to make scientificallysound comparisons between different genes, proteins, and species

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Question:

Pretend you are a medical researcher interested in theexpression and function of a particular human gene.

You are interested in comparing the gene withhomologous genes in other species, to compare theirsimilarities and differences. Which species would havea gene most similar to the human gene of interest?

a.) chimpanzee

b.) rat

c.) cow

d.) puffer-fish

Answer: it depends entirelyon which 2 genes you arecomparing. Speciesrelatedness alone is not areliable guide!

heart &skeletalmuscle

Nav1.5

skeletalmuscle

Nav1.4

PNS

Nav1.7

PNS

Nav1.9

PNS

Nav1.8

CNSPNS

embryonicCNS

CNSCNSPNS

Nav1.6Nav1.3Nav1.2Nav1.1

Example: Consider the voltage-gated sodium channels. Vertebrateanimals can have ten or more sodium channel genes in their genomes,each of which has specialized expression in different excitable tissues.

Gene nomenclature and expression profile in mammals.CNS=Central Nervous System. PNS=Peripheral Nervous System.

Chromosomal locations: Blue, HC2; Black, HC17; Orange, HC3; Green, HC12

Because of gene families, a human sodium channel genecan be more closely related to a sodium channel gene inanother species, than to another sodium channel in thehuman genome. For example, Nav1.4 (from skeletalmuscle) is more closely related, evolutionarily, to theNav1.4 gene of fish, than it is to any other human gene.

The common ancestor tofish and mammals hadonly four of these genes.Gene duplicationsoccurred in the twolineages after theevolutionary split betweenthem. This is what thephylogeny looks like, for 10mammalian genes and 8fish genes. Depending onwhich pair of genes youcompare, sometimes amammal gene is moreclosely related to a fishgene, than to anothermammal gene.

Copy A Copy B

Gene duplication

Original gene

Duplication event

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So why are they interesting?

• New gene functions

• Gene duplications structure genomes

• Important for comparative genetics

Orthology and Paralogy

A B C1 2 34 5 6

1 2 3 4 5 6OrthologousOrthologous

Paralogous

α β

Gene duplication

Why orthology matters

• Inference of structure or function isbest made between orthologoussequences (paralogues may be moregreatly divergent).

• For phylogenetic analyses, inference ofspecies relationships should be basedon orthologous genes






- Phylogenetic information plus knowledge of coevolutionary symbioses canhelp in the design of strategies for biological control of agricultural pathogensand pests

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USING PHYLOGENY FOR BIOPROSPECTING

Many plants and animals are beneficial to human beings formedicine, or for biological control of pests, parasites, or pathogens

Phylogeny can help guide a search for potentially beneficial speciesbased on what is known about their close relatives

1 2 3 4 For example, if a valuable medicine canbe produced from natural compounds inplant species 3, it would make sense tosearch for similar compounds in theclosely related plant species 4.Or, if wasp species 3 helps control pestcaterpillar C, then wasp species 4 may bea good candidate for natural control ofpest caterpillar D.

A B C D Phylogeny reveals specialized parasite/hostrelationships. Eucharatid wasps can be used forbiological control of imported red fire ants






- Phylogenetic information plus knowledge of coevolutionary symbioses canhelp in the design of strategies for biological control of agricultural pathogensand pests

- To conserve biological diversity in threatened ecosystems or habitats,phylogeny can aid in selecting priority species for monitoring and protection

For example: frogs areundergoing a worldwidemass extinction, due toseveral factors. It isunlikely that we can savethem all -- but whichones should we save?

Use phylogeny tochoose conservationstrategies that maximizebiological diversity… andchoose geographicareas that contain themost diversity

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The clouded leopard(Neofelis nebulosa)lives in parts ofsoutheast Asia,Malaysia, andIndonesia.

The clouded leopard was long treated as a single species,but recent phylogenetic analyses indicate that leopards onBorneo and Sumatra are different. This is supported by newmorphological evidence as well.

As a result of information provided by phylogeny, twospecies are now recognized and have separate conservationstatus. The new species Neofelis diardi has even beendesignated into Sumatran and Bornean subspecies.

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