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EEB210/396 Spring 2007

Class #26: Darwinian Medicine

Genetic diseases:

Why are some deleterious genes maintained in the population at significant frequencies?

a. some have pleiotropic effects: sickle cell anemia results from a recessive gene but when this gene is present in heterozygous state it confers some resistance to malaria---sickle cell gene leads to a single amino acid substitution in the hemoglobin molecule, and this leads to a change in configuration of the molecule and a change in the shape of red blood cells (sickling)---the sickle cell gene is most common in areas where malaria is prevalent

b. some genes do not manifest deleterious effects until reproductive life is essentially finished: Huntington’s chorea results from a dominant gene and the disease is usually fatal, but symptoms usually do not appear until after 35 years of age. The incidence in the U.S. is 5.15/100,000 births.

It is important to look for pleiotropic effects of other genes that lead to genetic disease

Pathogen-host interactions:

In co-evolutionary competition between pathogens and their hosts it is important to consider the relative generation times of each---generally pathogens have much shorter generation times than their hosts and thus can evolve faster and avoid host defenses

Old theory was that pathogens should evolve to be benign rather than virulent because they must be passed from host-to-host (therefore, it is best for the pathogen if it does not debilitate or kill the host); nevertheless, whereas many human pathogens are benign (i.e., common cold, most strains of influenza), others are extremely virulent (malaria, some strains of influenza)

What is the cause of virulence? Toxic substances produced by pathogens, tissue damage, etc. But, in general, a rapid rate of pathogen reproduction is likely to lead to virulence. Thus, other factors being equal, a particular type of bacterium or virus is most likely to be virulent if it reproduces rapidly. And rapid reproduction can have obvious advantages for the pathogen.

Paul Ewald: Proposes that pathogens that are transmitted by vectors (intermediate hosts) will tend to evolve to be more virulent as compared to pathogens that are transmitted directly from person-to-person (i.e., compare malaria to colds, influenza): 2

a. consider the virulence of diseases like malaria and yellow fever (bacteria transmitted by mosquitoes), sleeping sickness (bacterium transmitted by tsetse fly), and Lyme disease (transmitted by deer tick)

b. cholera also a very virulent disease, transmitted via the water supply (i.e., water supply essentially acts as a vector)---caused by the bacterium, Vibrio cholerae---the bacterium produces cholera toxin, which interacts with G proteins and cAMP in the lining of the intestine to open ion channels and lead to diarrhea

First known cholera pandemic was in 1816-1826 in India, with the Ganges River likely serving as a source of spread of the disease---later pandemics in Europe, Russia, North America, where it was spread mainly through water supplies that were not adequately filtered and chlorinated

It has been known for some time that certain pathogen-linked diseases show up in more virulent forms in hospitals as compared to the general population. Ewald suggest that this may be because hospital personnel act as vectors, transmitting the pathogen from patient-to-patient. Ewald also speculates on the appearance of the world-wide influenza epidemic of 1918, involving an especially virulent strain of the flu virus and resulting in deaths of over 20 million persons. The 1918 virus strain apparently originated in the trenches of WWI and/or in army hospitals. In these situations, persons were crowded and transmission from person-to-person was easily accomplished (from the point of view of the virus). Thus, there would be little “penalty” to a virus strain that became virulent, debilitating and even killing its host in a relatively short time. In less crowded conditions, debilitated hosts would be less likely to transmit the virus, so a virulent strain would be less likely to prosper.

In making decisions regarding treatment of pathogen-caused diseases, it may be important to distinguish between symptoms that are simply a direct result of pathogen activity vs. symptoms that represent a host defense mechanism:

a. fever is now thought to be a host defense mechanism that may aid in combating certain pathogens---much of current thinking about function of fever started with experiments in lizards, showing that when infected with a pathogen they would seek a source of heat and that by warming themselves they would increase resistance to the pathogen

b. coughing and sneezing help to rid the lungs and air passages of pathogens, but these reactions also help to transmit air-borne pathogens from host-to- host (so it would not be surprising if some pathogens that reside in the air 3

passages might evolve mechanisms to stimulate coughing and sneezing by the host) Many pathogens are able to change the behavior of the host organism in ways that facilitate transmission of the pathogen to another host: For example, one type of fluke infects ants and then sheep in two life-cycle stages. When the fluke has infected an ant, it alters the ant’s behavior so that the ant climbs to the top of a blade of grass where it is most likely to be ingested by a grazing sheep. Another type of fluke that infects snails causes the same type of behavior in the snail, so that the snail is more likely to be eaten by a bird, which is the secondary host for the fluke. Rabies virus enters an animal through the skin and then enters nerves and is transported through nerves into the brain. The virus can reach the salivary glands and lead to increased salivation and in the amygdala of the brain to stimulate aggression. Thus, the rabid animal will bite other animals and transmit the virus via the saliva.

Researchers have taken advantage of the characteristics of rabies virus to be transported in retrograde fashion in the nervous system (that is, transported form peripheral to central nerves). Thus, rabies virus can be injected into a peripheral structure (for example, into the retina of the eye) of an experimental animal. After some time, the virus will be transported through nerves of the visual system. The animal can then be sacrificed and the brain examined to determine the pathway (retrograde tracing).

Human responses that might seem ‘poorly evolved’ but which likely have adaptive significance:

a. Margie Profet: Hypothesis that “morning sickness” during pregnancy is an evolved mechanism to reduce likelihood of mother ingesting substances that would be toxic to her developing fetus b. pain receptors---very important for protection from injury

Environmental novelty:

Some human diseases or pathological conditions may occur in surprisingly high incidence as a result of environmental novelty---Human environments have been changing at a very rapid pace, especially since the invention of agriculture about 10,000 years ago, leading to considerably higher concentrations of population and technological advances

It has been suggested that much obesity may be related to eating habits, such as preference for sweet foods, that may have been adaptive in our fruit-eating ancestors (who did not have access to plentiful supplies of prepared foods)