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Unformatted text preview: Sources of illness Why do we get sick? and Is it because of evolution? Genetic diseases Infectious organisms (e.g. bacteria, viruses, protozooans) p ) Environmental factors
Chemicals endocrine disruptors Radiation ozone hole Interactions of genetics and environment Human genetic diseases recessive allele
Sickle Cell Anemia Homozygous individuals affected About 1 in 500 children of AfricanAfrican-American origin affected Gene mutation expressed in protein synthesis
e.g., substitution of valine for glutamic acid at amino acid position 6 in hemoglobin protein results in expression of sickle cell disease Normal red blood cells Sickled Red Blood Cells 1 Human genetic diseases
Where did sickle-cell anemia sicklearise as a genetic disease?
About 10% of AfricanAfricanAmericans and 20% of Africans carry 1 copy of the sickle cell gene Malaria
Disease caused by protozooan Plasmodium sp. Tropical and subtropical Africa, Asia, South America Transmitted by Anopheles sp. mosquitoes What role does evolution play in it? Malaria
Initially anemia, fever, chills, sweating, nausea Enlarged spleen, liver Kidney problems hemoglobin in urine Clots - strokes Coma, death 400 million cases per year; 1-1.5 1million deaths, mostly children sporozoites g Plasmodium zygotes develop inside the gut of female mosquitoes. They become sporozoites, which migrate to the insect's salivary glands. sporozoites Malaria as a disease and the sickle cell gene
Severe malaria destroys red blood cells (RBC) and causes anemia Heterozygous genotype parasite enters RBCs and RBCs deform Destroyed by body and parasite cannot reproduce in blood stage of life cycle a Mosquito bites human, bloodstream carries the sporozoites to liver. d Some of the merozoites enter liver, cause more malaria episodes. e Others develop into male, female gametocytes that are released intobloodstream. b Sporozoites asexually reproduce in liver cells. merozoite f Female mosquito bites, sucks blood from infected human. Gametocytes in blood enter her gut, mature into gametes, which fuse to form zygotes. male gametocyte in red blood cell c Offspring (merozoites) enter blood, invade red blood cells, reproduce asexually. They can do so often, over a prolonged period. Disease symptoms (fever, chills, shaking) get more and more severe. 2 Interaction between malaria and the sickle cell trait
Phenotype: normal Prognosis: early death from malaria Interaction between malaria and the sickle cell trait
Under high selection pressure from malaria, the sickle cell trait is a positive In the absence of malaria, it's a negative it s The evolutionary "value" of a mutation is dependent on the environmental context! Genotype: ss yp
Phenotype: sickle cell disease Prognosis: early death from the disease Genotype: Ss
Phenotype: carrier Prognosis: resistant to malaria; few sickle cell symptoms Living with sickle cell disease
Advancements in treatment over the last 20 years all people with sickle cell disease to lead a relatively normal life Antibiotic treatments Immunizations Blood transfusions Hydroxyurea supplement Human genetic diseases
Sickle Cell Anemia Cystic fibrosis
Excessive secretion of very thick mucous by lungs, pancreas Homozygous recessive individuals are affected 1 in 2500 children of Caucasian origin are affected; 1 in 28 is a carrier 1 in 17,000 African-Americans African1 in 90,000 Asian-Americans Asian- Human Genetic Diseases
Most human genetic disorders are not evenly distributed across ethnic groups Geographic isolation of populations People with more recent common ancestors are more likely to carry a recessive allele than unrelated people Inbreeding increases chance of offspring homozygous for a recessive trait Human Genetic Diseases
Sickle cell anemia Cystic fibrosis
Hemophilia x-linked recessive Males affected frequently, females rarely Royal Family of England 3 Human Genetic Diseases Dominant disorders
Achondroplasia form of dwarfism; normal head and torso with short arms and legs Homozygous dominant is lethal to y embryo Heterozygous is affected Normal is homozygous recessive Lethal dominant alleles are less common than recessive alleles Cannot be carried by heterozygotes with causing an effect Human Genetic Diseases Other reasons
Down syndrome About 1 in 700 children in the US Extra chromosome 21 (trisomy 21) Caused b non-di j C d by non-disjunction of ti f chromosomes during meiosis Members of chromosome pair fail to separate Meiosis of chromosome 21 trisomy 3 chromosomes Sources of illness
Genetic diseases Infectious organisms ( g , ) (e.g. bacteria, viruses) Environmental factors Interactions of genetics and environment Response to an infection by a bacteria or virus Immune system successfully fights off invader Immune system fails; result is debilitation or death How does antibiotic therapy (=chemical warfare) affect this? 4 Antibiotics can assist the immune system in fighting the infection, IF:
Infection is fungal or bacterial Causative organism is susceptible to the antibiotic Antibiotic is i A tibi ti i given i hi h enough in high h dosage for long enough to kill (virtually) the whole population If it wasn't already too late when you began the antibiotic therapy Antibiotics are useless against the infection, IF: Infection is viral The bacteria or fungi are resistant to that particular antibiotic How do bacteria become resistant to antibiotics?
Spontaneous mutation: bacterial DNA may change spontaneously
e.g., Drug-resistant tuberculosis Drug- How do our actions magnify this evolutionary problem?
Wrong dosage or time course
MultiMulti-drug resistant tuberculosis in prisons Wrong disease
Antibiotics for the flu Transformation: uptake of naked DNA from the surrounding environment
PenicillinPenicillin-resistant gonorrhea Wrong animal
Heavy use in poultry feed Plasmid transfer: Plasmids are small rings of
DNA that can move from one bacterium to another In 1968, 12,500 died in Guatemala from Shigella diarrhea caused by a microbe with a plasmid that conferred resistance to four antibiotics All of which set up a natural selection environment that favors resistant genotypes! 5 From a local radio station morning show...
"I didn't feel that great this morning so I took some antibiotics I had left over from a previous prescription" What s wrong with this? What's
Didn't finish previous prescription No diagnosis for why he didn't feel well Perpetuates public misunderstanding of antibiotic use From a student
Wrestler small spot like a big pimple Grew to about 3" in one day Methicillin Resistant Staphylococcus aureus (MRSA) Treated with high-powered antibiotics highDeveloped 6 other spots during the season One could only be treated by IV vancomycin (last line of treatment) $1,000/session From a student
S. aureus infections range from impetigo to MRSA to flesh-eating fleshdisease to vancomycin-resistant vancomycinstrain Found in nursing homes, hospitals More common in wrestling rooms; hot , stagnant areas People need to be aware that these conditions and organisms exist What's News?
"Drug"Drug-resistant bacteria creeping beyond hospitals", Columbus Dispatch, 12 Jan 07, A5 Cancer patient chemotherapy, double mastectomy Then developed methicillin-resistant methicillinStaphylococcus aureus (MSRA) infection despite home health care 2 million Americans contract MSRA annually What's News?
90,000 deaths from MSRA infections Cases expanding beyond hospital athletic facilities, military bases, prisons Continued evolutionary arms race with bacteria Problem: pharmaceutical companies producing more lucrative drugs What's News?
Infectious Disease Society of America asked Congress to pass legislation providing incentives for developing new antibiotics Doctors think there are two strains:
Health care settings can get in blood and be fatal Skin infections 59% of skin infections in surgery rooms 6 What's News?
How can MSRA be treated?
HighHigh-powered IV antibiotics Some older penicillin-based antibiotics penicillinmay be effective 7 ...
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