Chapter 1 of Zimmer and Emlen text--The virus and the whale: how scientists study evolution.

Assigned readings

Chapter 1 of Zimmer and Emlen text--The virus and the whale: how scientists study evolution.

Biological evolution

Any change in the inherited traits (genetic structure) of a population that occurs from one generation to the next.

Note that evolution is a population process that occurs from generation to generation.

The above definition is a definition of Microevolution.

Biological evolution

The microevolutionary changes in genetic structure of a population over time can lead to substantial changes in the morphology of organisms over time and the origin of new species.

Such changes are referred to as Macroevolution.

Why study evolution?

Evolution explains the diversity of life. All living things are related to each other and are the products of millions of years of evolution.

Understanding evolution allows us to understand why the living world is the way it is. We can understand e.g., the similarities and differences between species, as well as their adaptations and their distributions.


There are also practical reasons to study evolution.

Evolution allows us to understand the evolution of disease organisms such as viruses and bacteria and combat them.


Evolution also gives us insight into such “big” questions as:

“How did we get here?” and “How did thought and language

evolve?”

Evolution case studies

Whales: mammals gone to sea Viruses: the deadly escape artists

How do we know whales are mammals?

Whales share synapomorphies (shared derived characters) with mammals› Mammary glands› Three middle ear bones› Single jaw bone (dentary)› Hair (in developing embryos)

Similarities with fish [streamlining, fins] arose through convergent evolution

Whale evolution

Whales are aquatic mammals that evolved from terrestrial ancestors through the process of natural selection by which individuals that possessed traits that best fitted them to life in water left behind the most offspring.

Fossil whales

The evolution of whales is well documented by fossil discoveries.

Modern whales have peg-like teeth or baleen for feeding. Early fossil whales such as Dorudon (40 mya) however had more complex teeth that were similar to those of contemporary terrestrial mammals.

Dorudon

Dorudon and modern whales share numerous features of the skull in common, including a distinctively thick-walled ectotympanic bone.

The same distinctive bone is found in Pakicetus a terrestrial wolf-like animal from 50 mya.

Pakicetus

Pakicetus also possesses a distinctive ankle bone called the astragalus. In Pakicetus it has a double-pulley like morphology and this structure is found only in artiodactyls (hoofed mammals such as cows, pigs and deer).

Fossils reveal links to land mammals

• Shape of astragalus connects to artiodactyls

These and other fossil discoveries have enabled biologists to construct a phylogentic tree (a tree of branching relationships) that depicts the evolutionary history of the group.

Evolution case studies

Whales: mammals gone to sea Viruses: the deadly escape artists

Viruses

Your text has a nice discussion of the evolution of the flu virus. You need to read it and be familiar with it.

We will discuss a different example in class– the HIV virus to illustrate the process of natural selection.

Natural History of HIV/AIDS

Acquired immune deficiency syndrome (AIDS) caused by Human Immunodeficiency Virus (HIV).

Disease first described in 1981. Transmitted through transfer of bodily

fluids. Immune system attacked. Victim dies

of secondary infections.

Scale of problem

More than 60 million people so far infected.

Mortality so far about 20 million. Projected mortality by 2020 --90 million

lives Responsible for about 5% of all deaths

worldwide. Approx. 8,000 deaths per day.

The Human Immunodeficiency Virus

HIV, like all viruses, is an intracellular parasite

Parasitizes macrophages and T-cells of immune system

Uses cells enzymatic machinery to copy itself. Kills host cell in process.

HIV binds to two protein receptors on cell’s surface : CD4 and a coreceptor, usually CCR5.

Host cell membrane and viral coat fuse and virus contents enter cell.

What the virus inserts

RNA genome Reverse transcriptase: transcribes viral

RNA into DNA Integrase: this enzyme splices DNA into

host DNA Protease: this enzyme involved in

production of viral proteins

Viral DNA inserted in host DNA produces HIV mRNA and all components of virus

Viral particles self assemble and bud from host cell.

HIV budding from human immune cell

HIV hard to treat

Because HIV hijacks the host’s own enzymatic machinery: ribosomes, transfer RNAs, polymerases, etc. it is hard to treat.

Drugs that targeted these would target every cell in the hosts body

Progress of an HIV infection

Three stages› Acute› Chronic› AIDS

Acute

Viral load increases rapidly CD4 helper T cell level declines Immune system mobilizes Viral load declines, CD4 T cell level

increases

Chronic

HIV not eliminated Viral load increases slowly CD4 helper T cell levels slowly decline

AIDS

CD4 helper T cell level drops so low immune system fails.

Patient vulnerable to all infections Life expectancy of only 2-3 years

How HIV causes AIDS

Human body responds to infection with HIV by mobilizing the immune system.

The immune system destroys virus particles floating in bloodstream and also destroys cells infected with virus.

Unfortunately, the cells that HIV infects are critical to immune system function.

How HIV causes AIDS

HIV invades immune system cells especially helper T cells.

These helper T cells have a vital role in the immune system.

When a helper T cell is activated (by having an antigen [a piece of foreign protein] presented to it, it begins to divide into memory T cells and effector T cells.

Memory T cells

Memory T cells do not engage in current fight against the virus.

Instead they are long-lived and can generate an immune response quickly if the same foreign protein is encountered again.

Effector T cells

Effector T cells engage in attacking the virus. They produce signaling molecules called chemokines that stimulate B cells to produce antibodies to the virus.

Effector T cells also stimulate macrophages to ingest cells infected with the virus.

In addition effector T cells stimulate killer T cells to destroy infected cells displaying viral proteins.

Why is HIV hard to treat?Viral disguise

First round of infection with HIV reduces the pool of CD4 Helper T cells (those that can recognize and attack HIV).

Loss of CD4 cells costly, but immune system now primed to recognize viral protein.

What’s the problem?


Virus mutates and the proteins on its outer surface (gp120 and gp41) change.

These surface proteins are not recognized by the immune systems memory cells.

Mutants survive immune system onslaught and begin new round of infection


Each round of infection reduces the numbers of helper T cells because they are infected by virus and destroyed.

Furthermore, because each lineage of T cells has a limited capacity for replication after a finite number of rounds of replication the body’s supply of helper T cells becomes exhausted and the immune system eventually is overwhelmed and collapses.

Why is HIV hard to treat?Drug resistance.

AZT (azidothymidine) was the first HIV wonder drug

It works by interfering with HIV’s reverse transcriptase, which is the enzyme the virus uses to convert its RNA into DNA so it can be inserted in the host’s geneome.


AZT is similar to thymidine (one of 4 bases of DNA nucleotides) but it has an azide group (N3) in place of hydroxyl group (OH).

An AZT molecule added to DNA strand prevents the strand from growing. The azide blocks the attachment of next nucleotide in the DNA chain.


AZT successful in tests although with serious side effects.

But patients quickly stopped responding to treatment.

Evolution of AZT-resistant HIV in patients usually took only about 6 months.

How does resistant virus differ?

The reverse transcriptase gene in resistant strains differs genetically from non-resistant strains.

Mutations are located in active site of reverse transcriptase.

These changes selectively block the binding of AZT to DNA but allow other nucleotides to be added.

How did resistance develop?

HIV reverse transcriptase very error prone.

About half of all DNA transcripts produced contain an error (mutation).

HIV highest mutation rate known. There is thus VARIATION in the HIV

population in a patient.

High mutation rate makes the occurrence just by chance of AZT-resistant mutations almost certain.

NATURAL SELECTION now starts to act in the presence of AZT

Selection in action

The presence of AZT suppresses replication of non-resistant strains.

Resistant strains are BETTER ADAPTED to the environment.

Resistant strains reproduce more rapidly. There is thus DIFFERENTIAL REPRODUCTIVE SUCCESS of HIV strains. Resistant strains produce more offspring.

Selection in action

Resistant strains replicate and pass on their resistant genes to the next generation.

Thus resistance is HERITABLE.

Selection in action

AZT-resistant strains replace non-resistant strains. The HIV gene pool changes from one generation to the next.

EVOLUTION has occurred: Remember EVOLUTION is change in the gene pool from one generation to the next.

Evolution of HIV population in an individual patient

Process of natural selection

There is variation in population – some members of population better adapted than others

That variation affects reproductive success – there is differential reproductive success as a result of natural selection.

Because the variation is heritable – beneficial alleles passed to offspring and alleles become more common in next generation.

Using selection to devise better treatment regimens.

Several different types of drugs have been developed to treat HIV.› Reverse transcriptase inhibitors (e.g. AZT).› Protease inhibitors (prevent HIV from

producing final viral proteins from precursor proteins).

› Fusion inhibitors prevent HIV entering cells.› Integrase inhibitors prevent HIV from

inserting HIV DNA into host’s genome.


Because HIV mutates so rapidly treatment with a single drug will not be successful for long.

Is there a better way?


Most successful approach has been to use multi-drug cocktails (referred to as HAART [Highly Active Anti-Retroviral Treatments]

HAART cocktails usually use three different drugs in combination (e.g. two reverse transcriptase inhibitors and a protease inhibitor).


Using multi-drug cocktails sets the evolutionary bar higher for HIV.

To be resistant a virus particle must possess mutations against all three drugs. The chances of this occurring is a single virus particle are very low.


If the same drugs were provided in sequence to an HIV population each time it faced a new drug it would need only a single mutation to gain resistance, which would then spread through the population.


Offering drugs one at a time is analagous to providing a stairway that HIV must climb. Offering multiple drugs at once requires HIV to leap from the bottom to the top in a single bound, which is much more difficult


Multi-drug treatments have proven very successful in reducing viral load and reducing mortality of patients.


However, HIV infection is not cured. Reservoir of HIV hides in resting white blood cells. Patients who go off HAART therapy experience increased HIV loads.


For patients on HAART whether HIV replication is stopped completely or not is crucial. In some HIV appears dormant and no replication means no evolution.

In other patients replication occurs, although slowly. However, this allows HIV to mutate and resistance to develop. So far, few HAART regimens are effective for more than 3 years.


Other downside of HAART therapy is that many patients experience severe side effects.

These patients have difficulties maintaining their treatment regimen.


Because of severe side effects of HAART therapy some doctors have advocated “drug holidays” for their patients (i.e. to have patients stop taking drugs for a while). From an evolutionary perspective does this seem like a good idea or not?

Origins of HIV

Where did HIV come from?

HIV similar to viruses in monkeys called SIV (simian immunodeficiency virus).

To identify ancestry of HIV scientists have sequenced various HIV strains and compared them to various SIV strains.

Origins of HIV

HIV-1 is most similar to an SIV found in chimps and HIV-2 is most similar to an SIV found in a monkey called the sooty mangabey.

Origins of HIV

HIV-1 occurs in three different subgroups (called M,N and O) and each appears closely related to a different chimpanzee SIV strain.

Origins of HIV

Thus appears that HIV-1 jumped to humans from chimps on at least 3 occasions.

Most likely acquired through killing and butchering chimps and monkeys in the “bushmeat” trade.

When did HIV move to humans?

Sequence data from several group M strains has been used estimate when HIV moved from chimps to humans.

Korber et al. (2000) analyzed nucleotide sequence data for 159 samples of HIV-1 strain M. Constructed a phylogenetic tree showing relatedness to a common ancestor of the 159 samples.

When did HIV move to humans?

Extrapolating based on rates of change of different strains suggests that subgroup M probably infected humans in the early 1930’s.

Benefits of evolutionary understanding

To summarize: our understanding of evolutionary biology has enabled us to understand why HIV is so hard to treat, devise treatment methods that take evolution into account and reconstruct the likley history of the disease.

Common misconceptions about Evolution

The process of Evolution is widely misunderstood and most people have only a vague understanding of the principle mechanisms (natural selection, genetic drift) by which it occurs.

As a result there are many misperceptions about how evolution occurs.

Evolution is “just” a theory

All scientific theories are backed by multiple lines of evidence› A theory is not just a “hunch.” All theories provide

broad, overarching explanations for major aspects of the natural world and have been extensively tested over time.

Other scientific theories› Gravity› Plate tectonics› Germ theory

Evolutionary theory is overwhelmingly accepted by scientists

Evolutionary biologists understand everything about the history of life

Biologists continually discover new information about life and the biological world.› All that new information fits or is

understood within the context of an evolutionary framework , because evolutionary theory provides a unifying framework for all biology.

Evolution explains the origin of life

Evolution deals with how life has changed after it originated

Other scientific fields address the origin of life, but an understanding of evolution especially the process of natural selection, is relevant to discussions of life’s origins.

Evolutionary biologists search for missing links

Newspaper reports always seem to focus on “missing links.” In reality, the fossil record is very incomplete and finding a direct ancestor of a particular organism is unlikely.

Available evidence strongly supports relationships between current and past species and fossil evidence sheds light on how traits evolved.

Evolution violates the second law of thermodynamics

The second law holds that disorder increases in closed systems (entropy always increases).

However, the Earth is not a closed system because the sun provides a constant input of energy.

Evolution is natural selection

Natural selection is a crucially important mechanism of evolutionary change but it is not the only one

Other mechanisms include:› Genetic drift› Sexual selection

Evolution is entirely random Evolution includes random and non-random

components› Mutations occur randomly› However, natural selection is completely non-

random and it results in the spread of mutations that increase the survival and reproduction of the organisms that possess them.

Convergent evolution also demonstrates that evolution is non-random › Phenotypes are predictable when environments

are similar

Organisms evolve adaptations they “need”

Evolution cannot identify or anticipate the needs of an organism› Mutations do not occur because they

would be adaptive in an environment› If beneficial mutations happen to occur by

chance they may increase in frequency through selection

Evolution is a march of progress

Evolution is not ladder-like› New species result from branching events› Evolutionary patterns are bush-like not ladder-like.

Evolution always moves from simple to complex

Evolution can also move from complex to simple› e.g. mitochondria evolved from free-living

bacteria› Parasitic tapeworms do not possess a gut

because they live attached to the intestines of their host and have no need to digest their own food. They just absorb predigested nutrients from their surroundings.

Evolution results from individuals adapting to environment

Evolution only works on inherited traits› Acquired changes are not passed to

offspring. No matter how much you practice a musical instrument you cannot pass that ability on to your child.

Populations evolve; individuals do not› Evolution results from changes in allele

frequencies that result from the success or failure of individuals to reproduce (e.g. as a result of natural selection or sexual selection)

Organisms are perfectly adapted to their environment

Natural selection can only work with available variation› Constrained by physical limitations and

development Many traits involved in trade-offs

› e.g. human brain size› Structures may have to perform multiple

different tasks and cannot be equally good at all of them

Evolution happens for the good of the species

Evolution selects traits that are beneficial for individuals or their genes› Traits that are bad for individuals (or

genes) will not be selected even if they are good for the species

Evolution promotes selfishness and cruelty

Natural selection favors traits that increase reproductive success› Different conditions select for different

traits› Cooperative traits are beneficial under

many conditions.› Cruelty is a human concept Nature is not

cruel. Rather Nature is pitilessly indifferent.

Evolution seeks peaceful harmony in nature

Natural selection favors traits that increase reproductive success› Can result in overexploitation of resources,

habitat destruction, the extinction of other species and many other non-harmonious outcomes.

Life can be divided into higher and lower forms

All of life is adapted to the environment in numerous ways› Environments differ so the adaptations to succeed

in different environments differ also.› One organism is not “superior” to another

organism just because we think it’s simpler. For example, a jellyfish is beautifully adapted to the role of a floating sit-and-wait predator even though it has no brain.

› Remember all living organisms are the product of many millions of years of evolution and it’s hard to improve them. That’s why most mutations are harmful.

Evolution has produced a stable diversity of life

Extinction means diversity is not stable› More than 99% of all species that have ever

existed are extinct.

› There has and always will be constant turnover in the diversity of life.

Chapter 1 of Zimmer and Emlen text--The virus and the whale: how scientists study evolution.

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Transcript of Chapter 1 of Zimmer and Emlen text--The virus and the whale: how scientists study evolution.