The 2011 UNM Evolutionary Medicine course meets for the first time today in Castetter Hall room 55. (The illustration above shows a timeline of first antibiotic use and date of first recorded antibiotic resistance – from Clatworthy et al. 2007 Nat Chem Biol 3, 541-8). In this class we will discuss antibiotic resistance and a wide variety of other evolutionary topics in medicine.

Click here for the complete syllabus: The syllabus for this semester is here: evo-med-schedule-2011 (and is located on the permanent link above).

The handout for lecture on 8/23/11: Evolutionary Medicine 2011

Readings (for next week)

1. The Great Opportunity: Evolutionary applications to medicine and public health. Nesse, RM and Stearns SC. Evolutionary Applications 1 (2008) 28-48.

Writing project (due next tuesday).

Give an example of gene-environment mismatch and modern illness.

In addition to the syllabus please read the following overview:

Evolutionary medicine principles can generate hypotheses to explain why we:

1) have body parts that are vulnerable to disease

2) suffer infectious diseases

3) are susceptible to diseases of aging (and more!)

Brief Overview of Topics that We Will Cover in this Course:

Evo Med hypotheses fall broadly into two main categories: Phylogeny and Fitness Effect

I. Phylogeny  (history)

How does evolutionary history explain a trait? For instance, “accidents of history” explain why we have a hole in our retina and why the spermatic cord punches an unnecessary hole in the abdomen, predisposing males to hernias.

1) Constraints include inverted arrangement of photoreceptor cells and ganglion cells whose axons carry the neural signals to the brain. Constraints can be thought of as by accidents of history. Early vertebrates likely featured eyes with this inverted arrangement of photoreceptors and transmitting neurons.  Octopus and squid have the opposite pattern. It is thought that the inverted photoreceptors may contribute to the likelihood of retinal detachments in humans and other vertebrates.

2) Demographic effects, such as population bottlenecks and the founder effect, can be grouped with phylogenetic explanations of traits. One example is provided by genetic diseases such as  Tay Sachs disease, which is common in Ashkenazi Jews, likely because of a founder effect.

II. Fitness Effect – (adaptive benefit)

What fitness benefit – often hidden – might be associated with a disease. Remember that the reproductive benefit, often does not accrue to the sufferer. The effect may be expressed in a pathogen, a sexual partner, in a different environment, or in someone with a different combination of genes.

Adaptation hypotheses include the following:

1) Mismatch: gene – environment mismatch and novel conditions (example: abundance of fast food restaurants and diabetes epidemic). In the Pleistocene, genes responsible for type II diabetes might have promoted survival. Potential reproductive benefit -> humans living hunter gatherer lifestyle.

2) Tradeoffs: tradeoffs involving host defense occur when host immune defense costs exceed benefits (example: Major Histocompatibility Complex – MHC – diversity promotes survival from infections. However, some combinations of MHC alleles are associated with auto-immune diseases. Benefit -> individuals with combinations of MHC alleles not shared by others. see also item 6.

Another category of tradeoffs involve somatic costs of traits that confer reproductive benefits. (examples include cancers of the reproductive tract; for example, without prostate glands there would be no prostate cancer but presumably less reproductive success as well.) Benefit -> individual reproduction at the expense of longevity. What do you think about the multiple effects of testosterone…?

3) Pathogen virulence strategies: disease severity relates to mode and frequency of transmission (vector-borne pathogens do not rely on host mobility for transmission and are often more virulent). Benefit -> pathogen.

4) Host-pathogen arms race: emerging diseases can reflect arms race involving one or more hosts (H1N1 influenza and West Nile Virus are examples). Deadly infections promote selection favoring increasingly costly host defenses (red blood cell mutations protect against malaria – see also item 6). Benefits -> compete between host defense and pathogen infectivity.

Those cancers that are caused by viruses, e.g. human papillomavirus and cervical cancer may reflect an arms race struggle. Benefit -> Virus

5) Genetic conflict in reproduction: placenta and embryo can cause maternal disease from imprinted genes derived from the father (examples include pregnancy induced hypertension, gestational diabetes, and Prader Willi Syndrome) Differing degrees of relatedness correlate with step-children’s risk of abuse. Benefit -> sometimes paternal-derived genes. These gene imprinting effects reflect an arms race between maternal and paternal derived alleles.

6) Balancing selection – The benefits of a trait, sometimes obscure, outweigh the disease-inducing costs. (example: heterozygote advantage for sickle cell trait. Sickle cell anemia kills most individuals who are homozygous for the trait and does not permit reproduction in most sufferers. Heterozygotes, however, do not get sick and are protected against falciparum malaria. The infection-fighting benefits for heterozygotes outweigh the mortality of sickle cell anemia in homozygotes. As a result of this balancing effect – tilted in favor of the heterozygote advantage- the sickle cell gene persists in populations exposed to falciparum malaria. The apolipoprotein E allele provides another possible example. Apo E is assoicated with Alzheimers disease, but may confer some benefits against pathogens. Benefit -> Individuals with certain combinations of genes.

7) Evolution of aging – antagonistic pleiotropy, the declining power of selection with age, as well as balancing selection, help explain the evolution of senescence. Benefit -> Age and lifecycle dependent: genes promoting youthful survival and reproduction are favored even if they cause illness and death later in life.

8 ) Cellular level reproductive advantage – uncontrolled cellular division is a feature of cancer. This process resembles natural selection, but of course the cellular lineage perishes along with its human “host”. Benefit -> time limited, usually dead-end lineages of cells. However, some cancers behave like infectious diseases, most dramatically illustrated in Tasmanian Devil facial tumors.

We will discuss hypotheses in all these categories during this course.

Writing Project grading:

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Joe Alcock

Emergency Physician, Educator, Researcher, interested in the microbiome, evolution, and medicine