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Health

Blacks get ill

Gene ExpressionBy Razib KhanMarch 4, 2008 1:05 AM

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There's a new paper which is getting some press buzz; here's a typical headline, Immune system differences found. That's as banal as can be: of course immune systems differ, there's a reason that MHC loci are very polymorphic. Our own immune diversity is the only way we can equalize the unfair "arms race" with the bugs who are always an adaptive peak ahead of us. It seems very likely that on the MHC loci many alleles become more fit as their frequency declines to very low levels because the pathogens which are optimized to "beat" them in the game of life can't find hosts and disappear. At that point the alleles can spread again until another round of adapted pathogens shows up, and so the game goes on and on. This eternal recurrence of evolution is why humans share some of these alleles with chimpanzees; that is, on one locus you may have a genotype which is like that of a chimp as opposed to your sibling! The high diversity is also why organ transplantation is such a touch-and-go affair. Matches on more loci means a progressively lower risk of massive rejection. But that's not why the paper, Evaluation of Genetic Variation Contributing to Differences in Gene Expression between Populations (Open Access), is getting a lot of press:

The researchers looked at expression levels - how active a gene is. They found significant differences, particularly in immune system genes involved in producing antibodies to combat bacterial infection. This backs up previous work which has shown African Americans may be more susceptible than Caucasians to infection, such as the gum disease bug Porphyromonas gingivalis.

Bingo, that's the big news! It shouldn't surprise you. Human populations have been subject to different pressures and have responded in kind. These pressures have had a major impact on the course of human history; the New World populations shrunk by 1-2 orders of magnitude in the generations after contact with the Europeans. In 1491 Charles C. Mann states that the native peoples were more well adapted to local parasites as opposed to pathogens. That might be due to the fact that the New World was relative free of human adapted pathogens for a host of reasons (e.g., few domesticates to jump from, lower population size and density, etc.).^1 Whatever the reason, it was, and it changed the course of human history. But there are inverted cases from that of the New World, where a new and highly deadly population invaded a new region where the locals were not ready for the pathogenic onslaught. One can make the case that the use of quinine, the first good treatment for malaria, was the necessary precondition for the Scramble for Africa. For centuries Europeans had been limited to coastal settlements characterized by high mortality rates, or restricted to less rigorous climes such as the Cape Colony in Southern Africa. Malaria kills. It seems possible that this disease is one of the most powerful selective forces in the last 10,000 years, spawning numerous biological responses on the part of humans. Of course Northern Europeans had none of these defenses (though some people from the Mediterranean did) because malaria was not endemic to the northern latitudes. This biological barrier meant that despite the fact that the European advantage over other peoples increased in the 19th century (China was defeated and India conquered in the first half of the 19th century^2), only near the end with the arrival of quinine could they leverage this in the "Dark Heart of Africa." It doesn't matter if you have a machine gun if you're dead within a month. Disease is ubiquitous. We all die, and quite often it is of disease. But it is also varied, and the shape of the attack determines the enormous range of responses. The same can be said of selective pressures in general. Placing different populations in the same environmental context, or even individuals, will result in the emergence of differences which can only attributable to varied genetic responses. Here's one that hits close to home, Why Is There Such A High Incidence Of Diabetes Among Asian Indians?:

The incidence of type 2 diabetes is rising, especially in urbanized parts of the world where sedentary lifestyles and obesity abound. In addition to weight and inactivity, race puts some people at increased risk for developing type 2 diabetes. The incidence of diabetes is rapidly increasing globally, and Asian Indians have the highest prevalence. An estimated 32 million Asian Indians have been diagnosed with this condition, and some experts expect this number to double over the next 30 years. ... The study yielded a number of interesting findings. Researchers observed that the Indian subjects, irrespective of their diabetic status, had a greater degree of insulin resistance than the American subjects of Northern European origin, even though the study subjects were not obese, a condition commonly associated with insulin resistance. Earlier research has established that people with insulin resistance typically have poorly functioning muscle mitochondria. Mitochondria are the part of cells responsible for converting energy from nutrients to ATP (adenosine triphosphate), the chemical form of cellular energy that the body uses for almost all functions. "Our study showed that the Indian diabetic and nondiabetic subjects with insulin resistance actually had mitochondrial function that was higher than those observed in the Northern European American subjects," says Dr. Nair. Dr. Nair hypothesizes that key to understanding this difference may lie in an examination of how populations adapt as they become more urbanized. Urban societies typically move away from lifestyles that involve a higher level of physical activity and diets dominated by low-calorie foods. "The higher capacity to produce ATP that the Indian subjects displayed may have been an adaptive advantage for the generations that preceded them, when energy content of their diet was lower. But today, this trait may be a disadvantage given the higher energy content of their current diets," explains Dr. Nair.

Remember how much Gandhi fasted? It's just too easy.... 1 - Native Americans did not bring many MHC variants to the New World, possibly because of the bottleneck, or possibly because they simply lost them over time due to lack of selective pressure. A good analogy to what happened are the diseases which can knock down monoculture fields, since the individuals are genetically very similar a highly efficient epidemic can result in the extinction of a whole population. 2 - In the case of India it was conquered in large part by native levies led by European or Eurasian officers. This might have blunted the affect of Indian diseases since you need just enough officers on the ground to maintain the colonial apparatus as opposed to a mass of troops.

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