Monday, June 11, 2007

Disease, genes, and evolution

Sometimes it’s good to be bad

As with many things in life, it turns out that the practice of combating disease is often not as clear cut as one would like to think. Yes, you would think a laceration needs sutured, an infection requires antibiotics, and high fevers have to be lowered. However, looking around the corner beyond the basic pathophysiology of disease you may be surprised to discover the long reach of evolutions shadow blanketing everything around you.

Life on this earth has proven to be tenacious, desperate, and highly adaptable grasping at whatever it can to survive by taking advantage of circumstances such as climateor beneficial genetic mutations to stay alive. This has been guided by natural selection which can be basically defined as the inherited differences in the chances of passing on genes (some genes are passed on better than others depending on the situation).

Among the primates, humans have a supreme ability to flex with the variations of environmental change. This has expressed itself by a rapid evolution over the ages-especially in recent times. It also suggests that humans have been under a very powerful form of natural selection. These forces have produced rapid changes in cranial size and leg length and may have opened opportunities for other selective forces(although other forms of genetic change-i.e., drift and "artificial"/cultural selection likely have played important roles). Studying genetic differences in today’s human population sheds light on these selective forces, among them something called directional selection. This is a type of selection that favors the propagation of one genotype over another leading to an evolutionary change. This particular form of selection is rare, but seems to have played a singular role in recent human evolution.

Among the factors influencing directional selection, the process of disease plays a surprising role in human development. For example, individuals of differing genotypes may have varying degrees of resistance to infectious diseases. This phenomenon implies that many diseases are evolutionarily associated with genes. For example, Steve Jones* states that: “Carriers of blood group B may be resistant to plague and this might possibly be why these types are common in areas of past epidemics. The Duffy blood-group cell surface antigen locus has two alleles, one of which (Fy-) is predominant only in West Africa. The distribution of this allele is associated with one form of malaria caused by the parasite Plasmodium. The parasite recognizes the Duffy antigen and uses it as an attachment site before burrowing through the membrane of the red blood cell. It is less able to attach to the Fy- antigen.”

Therefore, there can be a close tie between the relationship of disease prevalence and the genetic distribution of human populations. This interaction provides a potent force for directional natural selection. It implies that what can be good in a group of people in one given time and place can be the seed to major illness and even death in another time and place.

For example, populations living in tropical and subtropical countries commonly suffer from a number of serious blood diseases. The “pure” version of these maladies; the genetically homozygous individuals, are severely affected by an often fatal hemolytic anemia. South of the African Sahara; an area endemic with malaria, the sickle- cell gene is very common and up to 5-6% of newborns are affected with a severe homozygous form of sickle-cell anemia. What is interesting is that the heterozygous form of this condition confers an increased resistance to malaria resulting in a balance where, in spite of the severe cases, the general evolutionary population trend is to maintain a stable strategy sacrificing a few for the benefit of many. In areas without endemic malaria any version of the sickle-cell gene is disadvantageous.

Another interesting example of gene/ disease interaction is the fact that European populations are commonly affected by diseases such as dermatitis, asthma, and hay fever all of which have strong genetic links. Curiously, these genotypes seem to afford protection against intestinal parasite loads; a common cause of diarrhea and anemia (due to low standards of hygiene) common to most European populations until the last century. Today, their descendants are left with the historical legacy of many of these now hated common allergic diseases (often erroneously attributed to poor diet or mental maladies) that once conferred a general survival advantage to their ancestors.

This sets the stage for allowing many diseases to play the curious role of “savior” depending upon the presiding variables and directed selections. It is indeed important that this be taken into account when gaining insight on how to formulate therapeutic goals. There are diseases that have deep historical ties to events in humanities past, many of them unknown. Evolution has played a vital role in the distribution of many of these diseases through this convoluted history, how humanity has adapted to them, and how diseases have been turned into beneficial qualities in many circumstances. This comprehensive understanding provides unique and often critical insight into managing and dealing with those diseases that have a long, complex, and nuanced relationship with humanities struggle to survive.

*Ch7.6, Natural selection in humans. Jones,S. Human Evolution 9th ed.

Ref: Human evolution 9th ed. Jones, S, Martin, R, et al. Cambridge Univ Press. UK. 2004

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