Lecture 7 BIO200
Allele frequencies and populations
Evolution is defined as changes in allele frequencies over time within a population. If allele proportions change, evolution has occurred.
Allele frequency vs genotype frequency:
Allele frequency is the proportion of a given allele in the population, not a property of an individual. In a class example, the population of students shares a gene locus, but individuals have different alleles there.
For a gene like tongue-rolling, the allele for rolling (R) is dominant to the non-rolling allele (r).
Population example:
Population can be all students in a course section (e.g., bio 200 section A). They share the same gene locations, but differ in which alleles they possess.
If the dominant rolling allele (R) frequency is
and the recessive non-rolling allele (r) frequency is
then This ignores heterozygotes for simplification, used here for teaching the concept of allele frequencies.
Allele frequency interpretation:
Frequencies are the number of times an allele occurs in the population, represented as a proportion (typically a decimal).
The currency of evolution: the change in allele frequencies.
The five microevolutionary forces can change allele frequencies and thus drive evolution:
gene flow
nonrandom mating
genetic drift
mutation
selection (not covered in depth in this lecture; saved for a later one)
Population vs. allele frequencies:
Population is a group of individuals of the same species; allele frequencies describe the population’s genetic makeup.
Allele frequencies are the currency of evolution because they reflect how the population’s genetic variation changes over time.
Gene flow
Definition: movement of alleles from one population to another, typically via migration of individuals or their gametes.
Simple intuition: alleles move among populations when individuals migrate.
Example (flowers):
Meadow A has white flowers due to a recessive allele (ww). Dominant yellow allele (W) is in another meadow B, where flowers are yellow.
A bee moves pollen from meadow B to meadow A. If pollen from yellow flowers (W) fertilizes white flowers (ww), some yellow alleles appear in meadow A, changing allele frequencies and causing evolution.
Key point: gene flow changes allele frequencies between populations; the original rates depend on migration distance, pollination vectors, and distance between populations.
Nonrandom mating
Nonrandom mating vs random mating:
In random mating, every allele has an equal chance of pairing with any other allele in the population.
Nonrandom mating occurs when phenotypically similar individuals mate more often than expected under random mating (assortative mating) or when dissimilar phenotypes mate more often (disassortative mating).
Assortative mating (like-with-like):
Increases homozygosity, decreases heterozygosity.
If the trait has a genetic basis, assortative mating raises homozygote frequency and lowers heterozygote frequency.
Disassortative mating (opposites attract):
Increases heterozygosity, decreases homozygosity.
Practical example: humans often mate with partners of similar height, leading to more similar-height gene variants pairing and increasing homozygosity for height-related genes.
Extreme case: self-fertilization (common in some plants and hermaphroditic animals) drastically reduces variation because there is no new combination of alleles from different individuals.
Quick recap:
Assortative mating increases homozygosity and decreases heterozygosity.
There is no separate widely used term for disassortative mating; some instructors call it “opposites attract.”
Nonrandom mating changes genotype frequencies without necessarily changing allele frequencies unless it alters heterozygosity distribution over time.
Genetic drift
Genetic drift is a random force that changes allele frequencies due to sampling effects in small populations.
Two main mechanisms: 1) Founder effect: a new population is started by a small number of individuals who carry only a subset of the original population’s alleles.
Example: lizards on a log drift downstream and establish a new island population with a random subset of alleles. A rare mutation (e.g., blue toes) could become common purely by chance in the new isolated population, illustrating evolution by drift.
Distinction from gene flow: in founder effect, the new location does not already contain a population of the species; hence it is not gene flow.
2) Bottleneck effect: a drastic reduction in population size (e.g., a tidal wave reducing penguin numbers) leaves a small surviving subset with a different allele frequency from the original population.As the population recovers, allele frequencies may differ from the original.
Effectiveness of drift depends on population size:
Drift is less powerful in larger populations because sampling variation averages out over more individuals.
Summary: genetic drift causes random, environmentally independent changes in allele frequency in small populations, via founder effects or bottlenecks.
Mutation
Mutation is the ultimate source of genetic variation; without mutation, there would be no new variation for evolution to act upon.
Mutation rate and impact:
Mutation events are rare; typical gene mutates about once every cell cycles.
Most mutations have small or no effect on the organism.
How mutations affect gene expression and protein sequences (context from Crick & Brenner):
The genetic code is read in triplets (codons). Since there are 4 nucleotides, 4^3 = 64 possible codons, which is more than enough to encode 20 amino acids, implying the code is degenerate (multiple codons code for the same amino acid).
Codons are read in a reading frame; there are no spaces between codons in the reading frame. The start codon sets the reading frame for all subsequent codons.
If nucleotides are added or removed, the reading frame can shift (frameshift mutation). Frameshifts are particularly disastrous when they occur early in the sequence because downstream codons are read in the wrong frame and premature stop codons often arise.
In contrast, deleting or inserting a multiple of 3 nucleotides (3, 6, 9, …) removes or adds whole amino acids without shifting the reading frame, so the downstream codons remain in frame (though the protein sequence is altered).
Types of single-nucleotide substitutions (point mutations):
1) Silent (synonymous) mutation: the same amino acid is encoded due to degeneracy; often no functional change.
2) Missense mutation: a different amino acid is substituted, which can disrupt protein function depending on position and role of the amino acid.
3) Nonsense mutation: a stop codon is introduced in place of an amino acid, truncating the protein and usually abolishing function.These point mutations can be categorized as either:
Frame shifts (deletions/insertions not in multiples of 3) → alter reading frame and often terminate translation early.
Substitutions (base substitutions) → silent, missense, or nonsense outcomes.
Chromosomal mutations (larger-scale changes):
Deletions: large segments of a chromosome are missing (chromosome-level deletions).
Duplications: a chromosome region is copied one or more times.
Inversions: a chromosome segment is cut out, reversed, and reinserted, changing gene order.
Translocations: a piece of one chromosome breaks off and attaches to a different chromosome.
These chromosomal changes can disrupt gene function or regulation, and may drive larger phenotypic shifts.
Aneuploidy and polyploidy:
Aneuploidy: abnormal number of chromosomes in a cell (e.g., monosomy - missing a chromosome; trisomy - an extra chromosome).
Nondisjunction: failure of homologous chromosomes or sister chromatids to separate during meiosis, leading to aneuploid gametes and zygotes.
In humans, many aneuploid conceptions do not survive; monosomies are often lethal, but some trisomies survive (notably trisomy 21, Down syndrome).
Common aneuploidies in sex chromosomes include Turner's syndrome (XO) and Klinefelter syndrome (XXY); Turner's is usually more severe than Klinefelter.
The incidence of aneuploidy is surprisingly high: estimates suggest about 5 ext{ %} of all conceptions involve aneuploidy, with many conceptions terminated before pregnancy is recognized.
Polyploidy: duplication of the entire genome. In animals, often lethal; in plants, common and evolutionarily important. Example: bananas can be diploid (2n), triploid (3n), tetraploid (4n), pentaploid (5n), or higher.
Outcomes of mutations (three broad categories):
Harmful (often deleterious or lethal)
Neutral (no fitness effect; includes silent mutations or duplications in noncoding regions)
Beneficial (improve fitness and can fuel adaptive evolution; though potentially rare)
Protein-level or phenotypic changes can arise from any of the above mutations, providing the raw material for natural selection. While beneficial mutations may be rare, when they arise and spread, they can have large population-level effects.
Important connections:
Mutations generate new alleles; without mutation there is no new variation for selection or drift to act upon.
The vast majority of mutations are neutral or slightly deleterious; beneficial mutations are the primary driver of rapid evolutionary shifts when they occur and are maintained by selection.
Frameshift mutations are especially disruptive if they occur early in a gene, because they alter every downstream codon and frequently introduce a premature stop codon.
Quick question example recap (conceptual):
If a DNA sequence is transcribed and a single nucleotide is altered (as in the example with ACG vs ACA), sometimes the amino acid remains the same (silent mutation) due to codon degeneracy, leading to no change in the protein.
If a single nucleotide change changes an amino acid, this is a missense mutation; if it creates a stop codon, it is a nonsense mutation.
Chromosomal mutations and aneuploidy in depth
Chromosomal-level changes and their potential impact:
Deletion: loss of a large DNA segment; can be fatal or disrupt multiple genes.
Duplication: copy of a region; copy number variation can alter gene dosage and phenotypes.
Inversion: a chromosomal segment reverses orientation; effect depends on whether it disrupts gene function or regulatory elements.
Translocation: segment moves to a different chromosome; can disrupt meiosis by preventing proper homologous pairing.
Nondisjunction: failure of proper chromosome separation during meiosis; produces aneuploid gametes.
Aneuploidy and its clinical relevance:
Monosomy: monosomy of a chromosome (e.g., XO) often results in severe health consequences or lethality.
Trisomy: an extra chromosome (e.g., Trisomy 21, Down syndrome) can be viable; other trisomies are typically lethal.
The presentation of sex chromosome aneuploidies (e.g., Klinefelter XXY, Turner's XO) shows variable phenotypes and survival.
Polyploidy in evolution:
Whole-genome duplication (polyploidy) can occur due to errors in meiosis or hybridization between species.
In animals, polyploidy is rare and often lethal, but in plants, it is common and can contribute to speciation and novel traits.
Example: bananas can be diploid (2n), triploid (3n), tetraploid (4n), pentaploid (5n), and so on, with different ploidy levels affecting fertility and fruit characteristics.
Outcomes and significance for evolution
Three broad outcomes of mutations in the context of evolution:
Harmful mutations: often reduce fitness or are lethal.
Neutral mutations: do not affect fitness or have minor/no effect on phenotype (e.g., silent mutations, noncoding changes, or inversions that do not disrupt function).
Beneficial mutations: enhance fitness; although rarer, they can be the key fuel for adaptive evolution.
The role of mutation in evolution:
Mutation is essential as the source of new genetic variation; without it, other microevolutionary forces would have nothing to act upon.
The balance between mutation rate, selection, drift, and other forces shapes the evolutionary trajectory of populations.
Reading frame, codons, and the nature of the genetic code (context from Crick and Brenner)
How codons were inferred to be read in triplets:
With four nucleotides and twenty amino acids, a one-to-one or a two-nucleotide-per-amino-acid code would be insufficient. Three nucleotides per codon provide 64 possible codons, enough to encode all 20 amino acids and some stop signals.
Code degeneracy: more than one codon codes for the same amino acid; e.g., four different codons code for proline.
Reading frame and starting point:
The start codon defines the reading frame; shifting the reading frame by even one nucleotide changes every downstream codon, often catastrophically.
Frameshift mutations occur when a single nucleotide is inserted or deleted, shifting the reading frame; these can introduce premature stop codons and truncate proteins.
Crick and Brenner experiment (conceptual summary):
They deleted one, two, or three nucleotides in a viral RNA sequence and observed the effect on translation.
Findings:
Deleting 1 or 2 nucleotides changed downstream codons, indicating reading frame dependence.
Deleting 3 nucleotides removed one amino acid but kept downstream codons in the same frame, supporting that codons are read in triplets and that there are no spaces between codons.
Stop codons and frameshifts:
Among the 64 codons, some are stop codons; frameshifts early in translation increase the likelihood of premature termination, severely affecting protein production.
DNA to RNA to protein flow (central dogma) and mutations:
DNA (template strand) in the nucleus is transcribed into RNA, which leaves the nucleus to be translated into a protein.
The central dogma underpins how mutations at the DNA level can influence the protein product and phenotype.
Mutations and reading frame in practice:
Example from class: a single base substitution at a codon position may be silent if the codon still encodes the same amino acid due to degeneracy; if not, it can be missense or nonsense depending on the codon change.
Key terms and quick reference
Allele frequency: proportion of a particular allele in a population.
Population: group of individuals of the same species living in the same area.
Microevolutionary forces: gene flow, nonrandom mating, genetic drift, mutation, selection (the latter covered in a later lecture).
Gene flow: transfer of alleles between populations due to migration.
Nonrandom mating: mating patterns that are not random with respect to genotype; includes assortative and disassortative mating.
Assortative mating: prefer mating with similar phenotypes/genotypes; increases homozygosity.
Disassortative mating: prefer mating with different phenotypes/genotypes; increases heterozygosity.
Genetic drift: random changes in allele frequencies due to sampling error, pronounced in small populations.
Founder effect: new population established by a small subset, often with different allele frequencies than the original population.
Bottleneck: sharp reduction in population size, followed by recovery, with potential changes in allele frequencies.
Mutation: source of new genetic variation; can be point mutations or chromosomal mutations.
Point mutations: single-nucleotide changes (silent, missense, nonsense).
Frameshift mutation: insertion or deletion not in multiples of 3, shifts reading frame and often causes premature termination.
Chromosomal mutations: deletions, duplications, inversions, translocations.
Nondisjunction: failure of chromosome separation during meiosis, producing aneuploid gametes.
Aneuploidy: abnormal number of chromosomes in a cell; monosomy or trisomy.
Monosomy: missing one chromosome (2n-1).
Trisomy: an extra chromosome (2n+1).
Turner's syndrome: XO.
Klinefelter syndrome: XXY.
Polyploidy: multiple sets of chromosomes (e.g., 3n, 4n); common in plants.
Reading frame: the way codons are grouped into triplets starting from a start codon.
Degenerate code: multiple codons code for the same amino acid.
Codon length: 3 nucleotides per amino acid; total codons available: