We expect selection to keep lethal recessive alleles low in frequency

We expect selection to keep lethal recessive alleles low in frequency What explains these exceptions?

Tay Sachs due to Founders Effect parent population founders of new population FF FF FF FF FF FF FF FF FF FF Ff Ff FF Ff Ff Ff = 2/12 = 0.16 Ff = 2/3 = 0.67

Sickle cell trait due to Heterozyote Advantage aa Aa AA aa Aa AA What type of selection?

The sickle cell allele results from a single point mutation in the gene coding for hemoglobin dominant Negatively charged recessive Hydrophobic

With the changed amino acid, in low O2 situations the behavior of the molecule changes Normal Hb Mutant Hb Bonding forms chains

Sickled RBC Are more likely to burst Cause flow problems

Heterozygote Advantage Heterozygotes maintain a deleterious allele in a population These carriers typically do not express the disease Who are carriers? Which offspring has the disease?

Observed: tropical Africa harbors malaria Most common in Africa: 225million cases 781,000 deaths Mostly children, under the age of five. Fact Sheet. Us Global Health Policy. March 2011

The distribution of the sickle cell allele and the incidence of malaria are correlated Yellow = malaria zone Striped = sickle cell in high frequency

Aa aa AA Likely to die from malaria Dies from sickle cell disease Infected cells more readily sickle Sickling kills the parasite (low K+) Sickled cells removed in immune response

Both AA and aa children high risk of death; Aa beats both diseases

Sickle Cell trait (Aa) results in greater malaria survival – fewer infected cells, fewer sickled cells

Heterozygous Homozygous normal RBC Homozygous sickled

PRACTICE • If 9% of an African population is born with sickle-cell disease (ss), what percentage of the population will be more resistant to malaria because they are heterozygous (Ss) for the sickle-cell gene? • Use q2 approach

Practice • If 9% of an African population is born with sickle-cell disease (ss), what percentage of the population will be more resistant to malaria because they are heterozygous (Ss) for the sickle-cell gene? • q2= .09 • q = .3 • p = .7 • 2pq = 2(.7)(.3) = .42

Parasite • Vector • Host 4 species of Plasmodium Impacts mostly children, under the age of five. Anopheles mosquito 40 species transmit malaria

Global Malaria Eradication Program WHO 1955 • • DDT already available as an agricultural pesticide • • Success dependent upon, temperate climate, seasonal malaria cycle, good healthcare • • Successful eradication on islands : Taiwan, Jamaica

Problem : Natural selection • Reduction often followed by resurgence of now- resistant Anopheles populations Resistant Anopheles selected for

Evidence Conclusion Not possible to eradicate malaria In tropical areas how quickly the population evolves!

We expect selection to keep lethal recessive alleles low in frequency