The McDonald-Kreitman tests on genes from human and chimpanzee genomes revealed an excess of nonsynonymous variation within species. Dr. Noor proposed that this indicates numerous mutations persist without becoming fixed. In class, he suggested that this likely stems from our species' difficulty in eliminating some harmful mutations. Why is this elimination challenging?

The elimination of harmful mutations from a species is challenging for several reasons:

1. Large population size: Humans and chimpanzees both have large population sizes, making it harder for natural selection to effectively remove every instance of a harmful mutation. In a large population, even detrimental mutations can persist through genetic drift, which can overshadow the more subtle effects of selection.

2. Reduced effectiveness of natural selection: If a harmful mutation does not significantly reduce an individual's reproductive success, it may persist in the population. Some harmful mutations can be nearly neutral in effect, especially in a stable environment where there is less pressure to eliminate them.

3. Heterozygote advantage: In some cases, a mutation that is harmful in a homozygous state (where an individual has two copies of the mutation) may confer an advantage to heterozygous individuals (carrying only one copy of the mutation). This maintains the mutation within the population, as those heterozygous individuals have higher fitness.

4. Mutation-Selection Balance: There is a constant influx of new mutations in every generation. Natural selection works to remove harmful mutations, but as long as new mutations continue to arise, there will always be some present in the population. The equilibrium between the rates of new mutations and the rates of elimination by selection can lead to a persistent presence of harmful mutations.

5. Genetic linkage: Sometimes, a harmful mutation can be linked to a beneficial gene on the same chromosome, making it more difficult for natural selection to target and eliminate the harmful mutation without also affecting the beneficial one.

6. Variation in selection pressures: Different environments may exert varying selection pressures, which can change the fitness impact of mutations. This variation can prevent the consistent purging of certain mutations across the entire species range.