Lecture 43 Prof Duncan Shaw

Alleles & Fitness “Fitness” means the relative ability of organisms to survive and pass on genes Alleles can affect fitness: In most cases not at all (neutral) Sometimes to decrease it (deleterious) Very rarely to increase it (advantageous) The frequency of alleles in the whole population affects the health of the population, so it’s important to know about “population genetics”

Calculating Allele Frequencies We have a gene with alleles A and a Count number of individuals in population with each genotype: 300 AA 500 Aa 200 aa Allele frequency of A is (2x300 + 500)/2000 = 0.55 Allele frequency of a is (500 + 2x200)/2000 = 0.45

Allele & Genotype Frequencies In previous example, we had 300 AA, 500 Aa, and 200 aa individuals Genotype frequencies are therefore: 0.3 AA 0.5 Aa 0.2 aa Allele frequencies and genotype frequencies are related, but not the same thing

The Hardy-Weinberg Law Frequencies of alleles ‘A’ and ‘a’ are p and q, respectively (so p + q = 1) Calculation involving a Punnet square shows that genotype frequencies will be: AA p2 Aa 2pq aa q2 Also, p2 + 2pq + q2 = 1 These frequencies stay the same over time, if population is large, randomly mating, and alleles have same fitness Such a population is in “equilibrium”

Recessive alleles & carrier frequencies For a rare allele, heterozygotes (called “carriers” if the allele is recessive) are much more frequent than homozygotes: 2pq >>q2 Cystic fibrosis is caused by a recessive allele and affects 1/1700 Caucasian newborns: q2 = 1/1700 = 0.00059  q = 0.024  p = 1 - q = 0.976  2pq = 0.047 About 1 in 21 Caucasians is a carrier for CF

X - linked genes Males only have 1 copy of each gene on the X chromosome (“hemizygous”), from mother Therefore, for X-linked genes in males, genotype frequency is the same as allele frequency For rare X-linked recessive alleles, more males than females will be affected Example: X linked colour blindness affects 1/20 males q = 0.05 q2 = 0.0025 About 1/400 colour-blind females

Population Evolution Changes in the gene pool resulting a species adapting to its environment Dependent on genetic variation Driven by natural selection - differences in fitness make better adapted individuals more likely to pass on their genes Can be described in terms of allele frequencies in the population

Factors that change allele frequencies Mutation - formation of new alleles, leading to new capabilities of organism Migration - movement of individuals between populations Natural selection - different abilities of organisms to survive and reproduce Genetic drift - in small populations, random changes in allele frequency

Heterozygote advantage Sickle-cell anaemia is caused by a recessive allele - homozygotes have reduced fitness (without modern medical care), so it should disappear But heterozygotes have increased fitness - don’t have anaemia, but are more resistant to malaria than individuals without allele Distribution of sickle-cell anaemia in the world is similar to that of the malaria parasite, Falciparum