Ch 21.1 The Evolution of Populations - Genetic Variation Makes Evolution Possible

Darwin's theory of evolution by natural selection hinges on the presence of heritable trait variation within a population.
While Darwin recognized the importance of this variation, he lacked a detailed understanding of the mechanisms of inheritance.
Mendel's work on inheritance in pea plants laid the groundwork for understanding how genetic differences arise and are passed on.

Phenotypic Variation: Individuals of a species exhibit differences in observable traits (phenotypes).
- Examples in humans include facial features, height, and blood type.
- Phenotypic variation often reflects underlying genetic variation.
Genetic Variation: Differences in DNA sequences, including genes, among individuals.
- Some phenotypic differences are discrete (e.g., Mendel's pea flower colors, either purple or white, influenced by a single gene).
- Other traits show continuous variation (e.g., height), often due to multiple genes influencing a single trait (e.g., coat color in horses).

Gene Variability: Measured as the average percentage of heterozygous loci within a population.
- Heterozygous individuals have two different alleles at a locus.
- Homozygous individuals have two identical alleles at a locus.
- Example: Fruit flies (Drosophila melanogaster) are heterozygous at approximately 14% of their loci.
Nucleotide Variability: Measured at the molecular level of DNA.
- Much nucleotide variation doesn't result in phenotypic variation.
  - Many variations occur in introns (non-coding DNA sequences).
  - Even within exons (coding sequences), many variations don't alter the amino acid sequence of the encoded protein.
- Example: In a gene sequence comparison, only one out of 18 variable sites within exons resulted in an amino acid change, leading to two forms of the ADH enzyme.
- Only genetic variation that affects phenotype is exposed to natural selection.

Phenotype is a product of both genotype and environmental influences.
Phenotypic Plasticity: The ability of a single genotype to produce different phenotypes under different environmental conditions.
- Example: Caterpillars that develop different colors based on diet.
- Bodybuilders altering their phenotypes dramatically but do not pass their huge muscles on to the next generation.
Only genetically determined phenotypic variation is heritable and drives evolutionary change.

Genetic variation arises from:
- Mutation
- Gene duplication
- Other processes that produce new alleles and genes

Mutation: Changes in the nucleotide sequence of DNA.
- Caused by errors in DNA replication, UV light, radiation, or chemicals.
- A single base change (point mutation) can significantly impact phenotype (e.g., sickle cell disease).
- Most new mutations that alter phenotype are harmful because organisms are already adapted to their environments.
- Harmful recessive alleles can persist in diploid organisms through heterozygote protection, where their effects are masked by dominant alleles.
- This maintains a pool of alleles that may become beneficial if the environment changes.
Neutral Variation: Differences in DNA sequence that don't confer any selective advantage or disadvantage.
- Point mutations in noncoding regions often result in neutral variation.
- Redundancy in the genetic code can also lead to neutral variation, where amino acid sequence/protein function is not altered.
- Occasionally, a mutation can be beneficial and enhance reproductive success.
In multicellular organisms, only mutations in cell lines producing gametes are heritable.

Chromosomal changes (deletions, disruptions, rearrangements) are typically harmful. However, if genes remain intact, there may be no phenotypic effect.
Rarely, chromosomal rearrangements may be beneficial by linking genes in a positive way.
Gene Duplication: A key source of variation resulting from errors in meiosis (unequal crossing over), DNA replication slippage, or transposable elements.
- Duplication of large chromosome segments is usually harmful.
- Duplication of smaller DNA pieces can persist, allowing mutations to accumulate.
- This leads to an expanded genome with new genes that may acquire new functions.
- Example: Olfactory receptor genes in mammals have undergone many duplications, resulting in enhanced ability to detect and distinguish smells.
  - Humans have ~380 functional olfactory receptor genes.
  - Mice have ~1,200.

Organisms with short generation times can accumulate genetic variation more quickly.
Mutation rates are low in plants and animals ( $1$ mutation per $100,000$ genes per generation).
Prokaryotes and viruses have many more generations per unit time, leading to rapid genetic variation.
Example: HIV
- Generation time of ~2 days.
- RNA genome with high mutation rate due to lack of RNA repair mechanisms.
- Single-drug treatments are ineffective due to rapid proliferation of drug-resistant mutants.
- Drug cocktails (multiple medications) are more effective because it is less likely for mutations conferring resistance to all drugs to occur simultaneously.

Sexual reproduction shuffles existing alleles
Creates unique allele combinations.
Three mechanisms contribute to this shuffling:
- Crossing Over: Homologous chromosomes exchange alleles during meiosis.
- Independent Assortment: Chromosomes are randomly distributed into gametes.
- Fertilization: Random fusion of gametes from different genetic backgrounds.
These mechanisms rearrange alleles into new combinations each generation, generating genetic variation.
- Humans have 23 pairs of chromosomes.
- Independent assortment alone results in $2^{23} = 8,388,608$ combinations in each parent.
- When considering crossing over, the number of possible outcomes approaches infinity.