Recent Human Evolution to Altitude

Hypoxia on Cotopaxi

I took the above photo from 18,700 feet near the summit of Cotopaxi, an (active) volcano in the Ecuadorean Andes. We were suffering from a bit of exertional and hypoxic stress in this photo. On the other hand, native people of the Andes can cope with hypoxia at altitude better than us geentic lowlanders. How is this so? The evolutionary biology of high altitude peoples of the Andes, Himalayas, and Ethiopian Plateau is the topic for September 1st.

We will explore the different routes to physiologic adaptation to altitude in Tuesday’s class.

For discussion: How might gene-environment mismatch account for acute mountain sickness in Europeans? How many generations does it take to evolve solutions to the problem of living in a high altitude environment?

Updated! Writing assignment: Native people in the Ecuadorean Andes have more red blood cells than we do. Is that trait adaptive? What about Ecuadoreans who migrate to the US? Is that trait still adaptive? Can you think of any tradeoffs or downsides to having elevated numbers of red blood cells?

Handout for Tuesday’s lecture:

High Altitude Cultures

Readings for September 1st:

1. Beall

2. Genes at high altitude

3. Genomic Signatures Reveal High Altitude Adaptation

Optional altitude readings:

http://news.nationalgeographic.com/news/pf/92910801.html

A Novel Candidate Region for Genetic Adaptation to High Altitude in Andean Populations

Adaptation and Maladaptation to Ambient Hypoxia: Andean Ethiopian, and Himalayan Patterns.

All the way to senescence

Spawn til you die by Ray Troll

Spawn til you die by Ray Troll

Class, here is the link to Baba Brinkman’s ode to senescence (with lyrics):

http://music.bababrinkman.com/track/senescence

Understanding age-related risk of death and age-related disease are the result of tradeoffs and occur because of evolved life history traits.

We are going to cover evolutionary hypotheses of senescence for next weeks class. These hypotheses include antagonistic pleiotropy, declining power of selection, and mutation accumulation.  This link does a nice job of explaining the concepts.

Antagonistic pleiotropy is the concept that a gene for survival or a gene that promotes
reproduction early can be selected for even if it kills you at a later
age. So selection favors juvenile survival at the expense of old age survival. This hypothesis recognizes that most traits have both costs and benefits, and are tradeoffs. The tradeoff in antagonistic pleiotropy is improved health in youth, but disease in old age.

Haldane and Medawar proposed the declining power of selection hypothesis of aging. This proposes that genes for maintenance and repair of the body are selected for more strongly at early ages (pre-reproduction) than after reproductive age. For this: imagine a hypothetical gene that prevents cancer at age 10 and another gene that prevents cancer at age 100. The gene that prevents cancer at age 100 will not have any effect most of the time because most people are dead by age 100 (this remains true even if you take senescence out of the equation – random accidents will claim many lives). The gene that affects 10 year olds is more likely to be expressed and have a benefit simply because most people are alive at age 10. Therefore the old-age gene will be invisible to natural selection, the gene that affects 10 year old will be subject to positive selection.

Medawar extended his idea to include mutation accumulation. This idea posits that the body accumulates deleterious mutations at late ages that, because of the declining power of selection, are not selected against, and thus accumulate. In wild populations, not enough organisms reach advanced age, so these mutations are invisible. If allowed to achieve advanced chronological age, these mutations exert damaging effects, reducing fitness and contributing to senescence.

The disposable soma hypothesis is another idea to explain aging. This hypothesis recognizes that the nonreproductive part of the body (the soma) exists only to support the reproductive part of the body. At any moment in time an adult can devote energy to the maintenance of the body or to reproduction. Put simply, after successful reproduction, the soma is “disposable”, and genes are passed on. This tradeoff is vividly illustrated in adult salmon, which appear to do all their aging at once, immediately after a single reproductive effort. In many animals, bearing offspring shortens lifespan. There is some evidence of this in humans too.

For discussion:

Menopause is a strange phenomenon, because it represents premature aging of the female reproductive organs, asynchronous with the rate of decline in function for the rest of the body. It is paradoxical because it would seem that natural selection would favor maximal reproduction throughout the lifespan for humans. Given the fitness benefits of continued reproduction, why does the female reproductive organ age faster than the rest of the body? Humans are nearly unique in having a menopause; apparently killer whales are another example (see below).

Some suggest that menopause evolved because grandmothers are more successful at passing on their genes by investing in grandchildren than in more babies of their own. Others argue that menopause is a consequence of modern medicine prolonging the lifespan of women past 60 when most pre-historic women would be dead. So in the past reproductive aging would have been in sync with aging of the rest of the body. In this view menopause reflects the early mortality in pre-history and is a gene-environment mismatch.

Readings for next week:

1. Fabian, D. & Flatt, T. (2011) The Evolution of Aging. Nature Education Knowledge 3(10):9

2. Why do we age? Kirkwood Austad Nature 2000

3.  Menopause in killer whales

(Read also the Alcock and Schwartz 2011 and Stearns 2013 papers in the previous post.)

Optional Extra: as mentioned by James Gurney. His article, The Microbial Olympics

Here are the slides from the 8/18/15 class: Introduction to Evolutionary Medicine 2015

Writing Assignment, due Tuesday August 26th in class (Remember hardcopy only, and the assignment here is the correct one):

I want to know if humans are still evolving. What do you think? Specifically, do you think that modern medicine will affect human evolution? Will that evolution shape human longevity? (3/4 to 1 page total)

Extra credit: Do you think modern medicine will affect the evolution of human menopause?

Introduction to Evolutionary Medicine

Why is evolution important for medicine? Because evolution kills. Evolution also cures. We will explain in this first session.

For the first meeting of the 2015 Evolutionary Medicine Course we will define evolutionary medicine, give a broad overview, and discuss the evolution of antibiotic resistance.

JG

Special guest James Gurney PhD

We are also lucky to have research collaborator James Gurney join us on August 18 to describe our recent work using bacteriophages to combat a dangerous and increasingly common pathogen, Methicillin resistant Staphylococcus aureus (MRSA)

Phage

Each whitish circular colony is MRSA. The clear spots on the top row are caused by lytic bacteriophage. We are evolving bacteriophage to be a more efficient predator of MRSA in the lab at UNM.

The syllabus is here (subject to change):evo-med-schedule-2015

2015 Evolutionary Medicine Course

The 2015 UNM Evolutionary Medicine course begins in 1 week, August 18th, 2015!

If you are lucky enough to be enrolled, prepare to have your mind blown. You will learn:

  1. Amazing case studies that show why evolution matters to real patients.
  2. Cutting edge topics from expert guest lecturers in evolutionary medicine.
  3. Why evolution is indispensable for physicians and biomedical researchers.
  4. How we evolved with the human microbiome, with far-reaching consequences.
  5. And much more!

We will post the syllabus tomorrow, August 12, 2015. Check back soon.

Readings for next week include:

1. Alcock and Schwartz 2011 A clinical perspective in Evolutionary Medicine: What we wish we had learned in medical school. Evolution: Education and Outreach, 2011.

2. Stearns . Evolutionary Medicine: Its Scope, Interest, and Potential. Proceedings of the Royal Society B, 2013.

Obesity paradox: a benefit of fat in sepsis?

Screen Shot 2015-07-17 at 9.33.13 AM

Obesity is on the rise, as has been widely covered in the media and scientific literature. This would not be a problem, except that obesity is linked with increased diabetes and cardiovascular disease, and a higher rate of all-cause mortality. However, obesity is not all bad. In fact, the most exhaustive study of mortality and BMI showed a survival benefit for overweight and no increased mortality for mild (grade 1) obesity.  Indeed, for some conditions, it might be helpful to be fatter, a phenomenon known as the obesity paradox. The obesity paradox might be a factor in for patients with sepsis, bloodstream infections that are often fatal.

A study by Wurzinger and colleagues that was published in 2010 pointed to a survival benefit for larger people with greater BMI who have septic shock. Interestingly normal weight people had the highest mortality in this series of 301 septic patients. Overweight and obese subjects fared the best:

Screen Shot 2015-07-17 at 8.39.50 AM

With the usual caveats that this was an observational study and a relatively small sample at that, it does raise the possibility that fatter is better if you are unlucky enough to have a systemic blood infection and septic shock.

We have covered obesity in previous posts. A study by Wang and colleagues showed an increased risk of death from sepsis only among patients with the highest BMIs. In that study, only those in the population with a BMI greater than 40 indicating morbid obesity were more likely to become septic. The same study suggested that waist circumference was a better predictor of sepsis than BMI, per se. So, being fat itself up to BMI 40 may not be risky in terms of acquiring septic shock.

In addition to the Wurzinger study, another more recent observational study by Kuperman et al, indicated that survivors of sepsis had higher BMIs than nonsurvivors. (Interestingly, Kuperman’s results suggest that the benefit might be attributable to higher incidence of diabetes in the fatter group. That’s right, diabetes was linked with survival!) Wacharasint et al. (2013) published a similar survival benefit for obese septic patients. The survival benefit appears to be durable as well: Prescott et al. showed improved 1 year survival for obese ICU patients with sepsis. The biggest study examining sepsis mortality and BMI, involving 2882 subjects, was undertaken by Arabi et al. Like the others, this study showed improved survival in obese and very obese patients, although this effect disappeared when baseline characteristics were taken into consideration. Taken together, however, these results suggest that once septic, it might be of benefit to be fatter. Why might that be?

My colleague at the University of New Mexico, Jon Femling, has suggested that  increased blood lipids in the obese might be of benefit, by reducing virulence properties of invasive bacteria, such as Staphylococcus aureus. Higher levels of the blood Apoliprotein B, inhibit virulence gene expression in S. aureus, which might explain why trauma patients with higher Apo B suffer fewer infections.

Obesity, then, might benefit sepsis patients, because of virulence inhibition. We will explore alternative hypotheses in future posts.

Late breaking addition:

Interestingly, a recent study by Borel et al, showed that critically ill obese patients have a significant delay in the initiation of nutritional treatment (e.g. delayed calorie replacement). We have argued on this blog that full replacement of caloric needs might be harmful in the critically ill. Obese people may be buffered from the potential harm of malnutrition during critical illness, and the most likely to accrue an adaptive benefit from illness anorexia.

Wolbachia in the gut makes fruit flies wimpy

D. melanogaster

Rohrscheib et al have a recent paper in Applied and Environmental Microbiology showing a new way that microbes can manipulate host behavior.

Male Drosophila inoculated with Wolbachia were found to engage in fewer aggressive behaviors than uninfected controls. In effect, Wolbachia transformed male fruit flies into pacifists. How does this happen? The mechanism of passive behavior caused by Wolbachia involves downregulation of octopamine, a neuropeptide that has been previously shown to modulate aggressive behavior in fruit flies.

Read the entire paper here:

Wolbachia Influences the Production of Octopamine and Affects Drosophila Male Aggression

Read the abstract here: Continue reading

Less is more in blood transfusion

A recently published study in the Lancet continues to reinforce the view that less is more for blood transfusions.

Jairath and colleagues tested whether a restrictive approach (in which patients were transfused when hemoglobin concentration fell below 80 g/L) versus a liberal approach (in which transfusion was initiated when the hemoglobin concentration fell below 100 g/L). The liberal approach was not superior to the restrictive approach, suggesting we should tolerate lower hemoglobin levels in patients before starting blood transfusions.

As far as I know, most studies along these lines have shown either improved outcomes or no difference when restrictive transfusion thresholds are compared to liberal ones. These data support a less interventionist perspective on blood transfusion.

Read the Lancet paper here.