Monday, April 6, 2009
Diseases Causing a Selective Advantage
On page 176, Carroll talks about malaria, and how it has caused the sickle cell trait to become a selective advantage, as those with the sickle cell condition are somewhat resistant to malaria. Describe other instances in which widespread diseases have caused selective advantages in certain populations. Your discussion does not have to be limited to human examples.
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A good example of a disease causing selective advantages is Cystic Fibrosis. Cystic Fibrosis (CF) is disease affecting the respiratory and digestive systems. The body has channels in cell membranes that chloride ions flow through. In this lungs this washes away bacteria, mucus, and other debris. In the intestines it washes away pathogens and brings digestive enzymes in contact with food. In sweat glands, these channels recycle salt out of the glands and back into the skin. In a person with CF, mucus blocks these channels, meaning that the body cannot perform a lot of those vital functions. The mucus builds up in the lungs over time, and provides a suitable habitat for bacteria. In the small intestine the enzymes that break down fat can’t get to the food, and digestive problems may come up as a result. A person with CF is at risk to dehydration on a hot day.
ReplyDeleteWith all these harmful effects, it is a wonder that CF has stayed in the population for so long. It is, after all, a lethal disease, and is especially prevalent among Caucasians. Why has it not died out? In the US, Canada, and the UK, about 1 in every 2500 children are born with CF. 1 in 25 Caucasians are carriers of the gene that causes CF. This disease often kills its victims before they can even reproduce. For it to have survived for so long, it must have a selective advantage of some sort.
Turns out the mutant CF gene does possibly have some beneficial effects. In 1967 A.G. Knudsen, L. Wayne, and W.Y. Hallett published an article in the American Journal of Human Genetics. They found that, on average, the number of offspring for grandparents of CF children was higher (4.34) than the grandparents of a random control group (3.43), with 0.30 standard error. This implies that the CF gene is associated with successful childbirth.
More recently, there have been studies that suggested that CF carriers survive cholera at a relatively high rate compared to non-carriers. Cholera is a lethal disease. It produces a toxin that binds to the cell of the small intestine opening all of the transmembrane regulating ducts pumping out a lot of chloride ions and water- about 5 gallons per day. If the salt and water aren’t replaced quickly, the infected person will die of dehydration. Sherif Gabriel, a physiologist at UNC Chapel Hill, did an experiment with mice that carried the CF mutation and cholera. He found that the intestines of mice with cystic fibrosis infected with cholera secreted no fluid, unsurprisingly. The chloride channels were, of course, blocked. He discovered that mice that carried one CF gene secreted only half the liquid than the non-carrying mice. Gabriel concluded that when cholera infected humans that carried a mutant CF gene, only half as much fluid had to be secreted to flush the intestines of the toxin without leading to diarrhea, dehydration, or death. Cholera outbreaks happened most frequently among Europeans; this probably explains the high frequency of CF in Caucasian people.
http://www.smccd.net/accounts/hirzel/260/supplements/resources/cases/cftr3b.htm
http://www.cdc.gov/nczved/dfbmd/disease_listing/cholera_gi.html
http://en.wikipedia.org/wiki/Cystic_fibrosis
http://serendip.brynmawr.edu/biology/b103/f02/web1/emyers.html
http://www.sciencemag.org/cgi/content/abstract/sci%3B266/5182/107
Even though smoking is not a disease, it is a very hazardous activity that causes various diseases such as lung cancer and mouth cancer. There is an estimated 4.8 million deaths worldwide due to smoking. Even though smoking causes various diseases including cardiovascular diseases, chronic obstructive pulmonary diseases, and increase risk of infections, recent studies have shown that the immunosuppressive properties may be beneficial to some inflammatory diseases, such as hypersensitivity pneumonitis. Studies have shown that smokers have a lower serum antibody response to hypersensitivity pneumonitis-inducing agents. These findings suggest that smoking may inhibit the development of granulomatous inflammation. This can become a selective advantage to patients with hypersensitivity pneumonitis. When smoking causes lower serum antibody response, the
ReplyDeleteUsing the antigen Saccharapolysora rectivirgula to induce granulomatous inflammation in mouse and cell line models of disease, the investigators demonstrate that simultaneous nicotine exposure reduces the bronchoalveolar lavage cellular response, including the total lavage white blood cell and lymphocyte cell count, the extent of lung inflammation on biopsy, and interferon- but not interleukin-10 mRNA expression in the lung. Using a macrophage cell line treated concomitantly with lipopolysaccharide or Saccharapolysora rectivirgula and nicotine, decreased tumor necrosis factor protein, and tumor necrosis factor, interleukin-10, and interferon- mRNA were observed.
This study and others suggest that smoke and its components affect cellular constituents in bronchoalveolar fluid, with a relative increase in macrophages and a decrease in lymphocytes and dendritic cells. Relevant cellular functions are likely impaired, as macrophages demonstrate decreased antigen phagocytosis and clearance and T cells display altered antigen-mediated signaling and proliferation, indicative of impaired cell-mediated immunity. As evolution occurs by variation, selection, and time (Carroll 35), the different transcription of genes that make different proteins and antigens for cell-signaling may become a selective advantage for some inflammatory diseases such as hypersensitivity pneumonitis and become a genetic trait that was induced by the nicotine of cigarettes.
http://ajrccm.atsjournals.org/cgi/content/full/169/8/893
Even though smoking is not a disease, it is a very hazardous activity that causes various diseases such as lung cancer and mouth cancer. There is an estimated 4.8 million deaths worldwide due to smoking. Even though smoking causes various diseases including cardiovascular diseases, chronic obstructive pulmonary diseases, and increase risk of infections, recent studies have shown that the immunosuppressive properties may be beneficial to some inflammatory diseases, such as hypersensitivity pneumonitis. Studies have shown that smokers have a lower serum antibody response to hypersensitivity pneumonitis-inducing agents. These findings suggest that smoking may inhibit the development of granulomatous inflammation. This can become a selective advantage to patients with hypersensitivity pneumonitis. When smoking causes lower serum antibody response to hypersensitivity pneumonitis-inducing agents, smoking can actually, despite all of its other harmful effects, prevent the disease.
ReplyDeleteInvestigators have performed an experiment using the antigen Saccharapolysora rectivirgula to induce granulomatous inflammation in mouse and cell line models of disease. They have proven that nicotine reduces the bronchoalveolar lavage cellular response, including the total lavage white blood cell and lymphocyte cell count, the extent of lung inflammation, and interferon expression in the lung. Interferons stimulate the production of proteins in surrounding cells that inhibit viral replication, so the decrease in interferons decreases the sensitivity of cells towards foreign microbes. This decrease in sensitivity, thus, prevents the development of hypersensitivity pneumonitis. Also, using a macrophage cell line treated concomitantly with lipopolysaccharide or Saccharapolysora rectivirgula and nicotine, decreased tumor necrosis factor protein, and tumor necrosis factor, interleukin-10, and interferon- mRNA were observed.
This study and others suggest that smoke and its components affect cellular constituents in bronchoalveolar fluid, with a relative increase in macrophages and a decrease in lymphocytes and dendritic cells. Relevant cellular functions are likely impaired, as macrophages demonstrate decreased antigen phagocytosis and clearance and T cells display altered antigen-mediated signaling and proliferation, indicative of impaired cell-mediated immunity. As evolution occurs by variation, selection, and time (Carroll 35), the different transcription of genes that make different proteins and antigens for cell-signaling may become a selective advantage for some inflammatory diseases such as hypersensitivity pneumonitis and become a genetic trait that was induced by the nicotine of cigarettes.
http://ajrccm.atsjournals.org/cgi/content/full/169/8/893
Cystic Fibrosis is a lethal disease and many of the people who have the disease die before they may reproduce to pass on the disease. According to natural selection, the disease should have left the population long ago. Since CF still affects many people today it is suggested that it contains a selective advantage which allows the affected people to live longer and reproduce.
ReplyDeleteCystic Fibrosis is a disease that has been proven to cause selective advantages to an individual who has the disease. The cystic fibrosis transmembrance regulator is the gene that has a mutation to cause CF. This protein normally forms channels in the cell membrane for chloride ions to flow into the cell. When a person has CF they lack this ability and bacteria and mucus begin to build up inside their lungs.
The people who have CF have been noticed to have a greater success rate for having children. This would explain that people with CF can pass the disease to the next generation quickly. Another study found that a lethal disease was rarer in carriers of Cystic Fibrosis. Cholera causes dehydration of an individual by pumping out too much water and chloride. Also, hot climates are a disadvantage for people with CF, they become dehydrated much quicker then a normal person. CF may have lasted through the years because cold temperatures had a less affect on the person then warm temperatures. Cystic Fibrosis is lethal but protects against cholera and increase the success rate of childbirth. CF should have left the population due to selective advantages of people without the disease, but the selective advantages caused by the mutated gene have allowed the disease to continue to spread and be passed through the generations.
http://www.nytimes.com/specials/women/warchive/961203_1950.html
http://serendip.brynmawr.edu/biology/b103/f02/web1/emyers.html
The CCR5-d32 mutation is a mutation of the CCR5 gene. The CCR5 protein is a chemokine receptor in the CC chemokine group. The natural chemokine ligands that bind to this receptor are RANTES, MIP-1α and MIP-1β. CCR5 is mostly expressed on T cells, macrophages, dendrite cells and microglia, and it is thought to play a role in inflammatory responses to infection, though its exact role is unclear. Most highly concentrated in European populations, it has been traced back to the time of the Black Plague, leading scientists to believe that the Plague, in killing off 1/3 of the world’s population at the time, created a very strong natural selection coefficient for the mutation. Although it has a negative effect on the function of T cells, it provides protection from smallpox and HIV. It also appears to play a role in mediating resistance to the West Nile virus. It is found in 5-14% of European populations, but is very rare in Africans and Asians. Since HIV uses the CCR5 protein to enter cells, the mutation blocks HIV from entering the cell.
ReplyDeleteAs Theodore also pointed out, cystic fibrosis, as an extremely lethal disease, should have been selected against and died out long ago. But as it has not, the gene must have some benefit that caused to be selected for despite the disease. The cystic fibrosis transmembrance regulator mutant gene affects the CFTR protein that acts as a chloride ion channel in cell membranes, helping the lungs wash away mucus and the intestines move enzymes. Victims of cystic fibrosis have a build up of mucus in their lungs, forming a prime breeding ground for bacteria. Digestive problems arise when the enzymes cannot be brought in contact with food. The lethal strain of Cholera, Vibrio cholerae, makes a toxin that binds to the cells of the small intestine, opening all of the transmembrance regulating ducts pumping out large amounts of chloride ions and water, about five gallons a day. If the salt and water are not quickly replaced, the infected person dies of dehydration. With no ion channels, no fluid was produced. When cholera infected humans that carried a mutant CFTR, half as much fluid secreted may have been enough to rid the intestines of the toxin without resulting in diarrhea, dehydration and death. This selective advantage may have been what kept the CFTR mutant gene around.
http://en.wikipedia.org/wiki/CCR5
http://serendip.brynmawr.edu/biology/b103/f02/web1/emyers.html