Chapter 12: Genetics and Evolution

In the 1860s, an Augustinian friar named Gregor Mendel spent eight years crossbreeding pea plants in a monastery garden. He tracked seven traits - flower color, seed shape, plant height, and others - across thousands of offspring. What he discovered became the foundation of modern genetics.

Before Mendel, people assumed inheritance was like mixing paint. A tall parent and a short parent should produce medium-height children. Mendel proved this was wrong. Traits do not blend - they are passed as discrete units that we now call genes.

The Language of Genetics

Before diving into Mendel’s laws, you need the vocabulary. Every genetics question on the MCAT uses these terms.

Mendel’s First Law: The Law of Segregation

Each organism carries two alleles for every gene - one from each parent. During gamete formation (meiosis), these two alleles segregate so that each gamete carries only one allele.

Think about it at the cellular level: homologous chromosomes separate during anaphase I of meiosis. Since each homolog carries one allele for a given gene, the alleles end up in different gametes.

When two gametes fuse at fertilization, the offspring receives one allele from each parent, restoring the pair.

Mendel’s Second Law: The Law of Independent Assortment

Genes on different chromosomes are inherited independently of each other. The allele you inherit for seed shape has no influence on which allele you inherit for flower color - as long as those genes are on separate chromosomes.

This happens because homologous chromosome pairs line up randomly at the metaphase plate during meiosis I. Which maternal chromosome goes to which pole is independent for each pair. With 23 chromosome pairs, there are $2^{23}$ (over 8 million) possible gamete combinations - and that is before crossing over adds even more variety.

Mendel’s Law of Dominance

When Mendel crossed true-breeding purple flowers (PP) with true-breeding white flowers (pp), all F1 offspring were purple (Pp). The purple allele completely masked the white allele. He called purple “dominant” and white “recessive.”

When he allowed the F1 generation to self-pollinate (Pp x Pp), the F2 generation showed a 3:1 phenotypic ratio - three purple flowers for every one white flower. The white trait had not disappeared; it was simply hidden in the heterozygotes.

The underlying genotypic ratio in the F2 is 1:2:1 (1 PP : 2 Pp : 1 pp). Both PP and Pp look purple because P is dominant, giving the 3:1 phenotypic ratio.

DNA as Genetic Material

Mendel knew traits were inherited as discrete units, but he did not know what those units were made of. Three key experiments established DNA as the hereditary molecule:

Griffith’s Experiment (1928): Mixed heat-killed virulent (smooth) bacteria with live nonvirulent (rough) bacteria. The rough bacteria were “transformed” into virulent smooth bacteria. Something from the dead bacteria - a “transforming principle” - changed the living ones.

Avery-MacLeod-McCarty (1944): Identified the transforming principle as DNA. When they destroyed the DNA with enzymes, transformation stopped. Destroying proteins or RNA had no effect.

Hershey-Chase (1952): Used bacteriophages labeled with radioactive sulfur (for protein) and radioactive phosphorus (for DNA). Only the phosphorus-labeled DNA entered the bacterial cells and directed the production of new phages. This confirmed DNA - not protein - carries genetic information.

A Punnett square is nothing more than a multiplication table for alleles. One parent’s possible gametes go across the top. The other parent’s gametes go down the side. Each box represents one possible offspring genotype. If you can multiply, you can do genetics.

The Monohybrid Cross

A monohybrid cross examines the inheritance of a single trait. The classic example is Mendel’s flower color cross.

Cross: Pp x Pp (two heterozygous purple flowers)

• Genotypic ratio: 1 PP : 2 Pp : 1 pp (1:2:1)
• Phenotypic ratio: 3 purple : 1 white (3:1)

The 3:1 ratio appears whenever two heterozygotes for a completely dominant trait are crossed. Memorize this ratio - it shows up constantly on the MCAT.

The Test Cross

What if you see a tall pea plant but do not know whether its genotype is TT or Tt? Both look the same. To find out, you perform a test cross - crossing the unknown genotype with a homozygous recessive individual (tt).

• If the unknown is TT: all offspring are Tt (100% tall)
• If the unknown is Tt: offspring are 50% Tt (tall) and 50% tt (short) - a 1:1 ratio

A 1:1 phenotypic ratio in a test cross tells you the unknown parent was heterozygous. Test crosses are also called back crosses.

The Dihybrid Cross

A dihybrid cross tracks two traits simultaneously. This requires a 4x4 Punnett square (16 boxes) because each parent produces four types of gametes.

Example: Cross two plants heterozygous for both flower color (Pp) and plant height (Tt).

Each parent (PpTt) can produce four gamete types: PT, Pt, pT, pt.

The resulting 16-box Punnett square gives the classic 9:3:3:1 phenotypic ratio:

• 9 purple, tall (at least one P and one T)
• 3 purple, short (at least one P, homozygous tt)
• 3 white, tall (homozygous pp, at least one T)
• 1 white, short (homozygous pp and tt)

Probability Rules

You do not always need to draw a Punnett square. Two probability rules let you solve genetics problems faster:

The Product Rule (AND): The probability of two independent events both occurring is the product of their individual probabilities.

What is the probability of a child being Pp AND Tt from a PpTt x PpTt cross?

• P(Pp) = $\frac{2}{4}$ = $\frac{1}{2}$
• P(Tt) = $\frac{2}{4}$ = $\frac{1}{2}$
• P(Pp AND Tt) = $\frac{1}{2}$ x $\frac{1}{2}$ = $\frac{1}{4}$

The Sum Rule (OR): The probability of one event OR another mutually exclusive event occurring is the sum of their individual probabilities.

What is the probability of a child being homozygous (PP OR pp) from a Pp x Pp cross?

• P(PP) = $\frac{1}{4}$
• P(pp) = $\frac{1}{4}$
• P(PP OR pp) = $\frac{1}{4}$ + $\frac{1}{4}$ = $\frac{1}{2}$

Modified Ratios to Recognize

When you see a ratio that deviates from the expected 9:3:3:1, 3:1, or 1:2:1, it signals non-Mendelian inheritance. We will cover those in the next section, but here are the key modified ratios to watch for:

Chi-Squared: Does the Data Fit the Expected Ratio?

MCAT passages sometimes ask whether observed offspring match a predicted Mendelian ratio. The chi-squared (χ²) goodness-of-fit test is the tool.

You will rarely compute a full χ² on the MCAT, but you may be asked to interpret a p-value. The convention: p < 0.05 rejects the predicted ratio (something non-Mendelian is going on, like linkage or selection); p ≥ 0.05 says the data fit.

Mendel got lucky with his pea plants. Every trait he studied showed clean, complete dominance - one allele fully masked the other. But most real-world traits are messier. Sometimes neither allele wins. Sometimes both show up. Sometimes one gene blocks another gene entirely. These “exceptions” to Mendel’s rules are collectively called non-Mendelian inheritance, and they are heavily tested on the MCAT.

Incomplete Dominance

In incomplete dominance, the heterozygote phenotype is a blend of the two homozygous phenotypes. Neither allele is fully dominant.

The classic example is snapdragon flower color:

• RR = red flowers
• rr = white flowers
• Rr = pink flowers (intermediate)

The F2 ratio from crossing two heterozygotes (Rr x Rr) is 1:2:1 - one red, two pink, one white. Notice the phenotypic ratio equals the genotypic ratio because you can distinguish all three genotypes by phenotype.

Codominance

In codominance, both alleles are fully expressed simultaneously in the heterozygote. There is no blending - both phenotypes appear side by side.

The most important example for the MCAT is the ABO blood type system:

The $I^{A}$ and $I^{B}$ alleles are codominant with each other - a person with genotype $I^{A}$ $I^{B}$ expresses both A and B antigens. Both $I^{A}$ and $I^{B}$ are dominant over i, which produces no antigen.

This system also illustrates multiple alleles - there are three possible alleles ($I^{A}$, $I^{B}$, i) in the population, though any individual can only carry two.

Epistasis

Epistasis occurs when one gene controls or masks the expression of a different gene at a separate locus. The gene doing the masking is called the epistatic gene; the gene being masked is the hypostatic gene.

A classic example is coat color in Labrador retrievers:

• Gene E/e controls whether pigment is deposited at all
• Gene B/b determines whether the pigment is black or brown
• ee dogs are yellow regardless of their B genotype - the E gene is epistatic to B

If you cross two EeBb dogs, the expected 9:3:3:1 ratio becomes 9:3:4 because the 3 + 1 (both ee groups) are combined into a single yellow phenotype.

Polygenic Inheritance

Some traits are controlled by multiple genes, each contributing a small additive effect. These traits show a continuous distribution (bell curve) rather than distinct categories.

Examples: skin color, height, eye color, blood pressure.

Because many genes contribute, polygenic traits are strongly influenced by environmental factors. Height is polygenic, but nutrition also plays a major role - this is the nature vs. nurture interaction.

Pleiotropy

Pleiotropy is the opposite of polygenic inheritance: one gene influences multiple, seemingly unrelated traits.

The best MCAT example is sickle cell disease. A single point mutation in the hemoglobin gene causes:

• Sickle-shaped red blood cells
• Anemia
• Organ damage from blocked capillaries
• Resistance to malaria (in heterozygotes)

One gene, many phenotypic effects.

Penetrance and Expressivity

These two concepts describe how consistently a genotype produces its expected phenotype:

Penetrance = the percentage of individuals with a given genotype who actually show the phenotype.

• Complete penetrance (100%): Everyone with the genotype shows the phenotype (e.g., Huntington’s disease - if you carry the expanded repeat, you will develop symptoms)
• Incomplete penetrance: Not everyone with the genotype shows the phenotype (e.g., BRCA1 mutations increase breast cancer risk but not all carriers develop cancer)

Expressivity = the degree to which a phenotype is expressed among individuals who do show it.

• Constant expressivity: Everyone who expresses the trait shows it the same way
• Variable expressivity: The severity differs between individuals (e.g., neurofibromatosis type 1 - some patients have mild skin spots, others have debilitating tumors)

Genomic Imprinting

In imprinting, only the allele from one parent is expressed; the other is chemically silenced (methylated) during gamete formation. So phenotype depends on which parent contributed which allele, not just the genotype itself.

If the active copy is deleted or mutated, the silenced copy cannot compensate. Prader-Willi syndrome results from loss of the paternal copy of a region on chromosome 15; Angelman syndrome results from loss of the maternal copy of the same region. Same DNA region, different phenotypes, based entirely on parental origin.

Mitochondrial Inheritance

Not all genes are in the nucleus. Mitochondria contain their own circular DNA (mtDNA), which is inherited exclusively from the mother. Sperm contribute essentially no mitochondria at fertilization.

Key features of mitochondrial inheritance:

• Affected mothers pass the trait to all children (sons and daughters)
• Affected fathers pass the trait to no children
• There is no carrier state - you either have the mutation or you do not
• mtDNA does not follow dominant/recessive rules

Humans have 22 pairs of autosomes (non-sex chromosomes) and one pair of sex chromosomes. Females are XX. Males are XY. This unequal setup creates unique inheritance patterns for genes on the X and Y chromosomes.

Sex Determination

The SRY gene on the Y chromosome is the master switch for male development. It triggers testis formation, which leads to testosterone production and male sex characteristics. Without SRY, the default developmental pathway is female.

X-Linked Recessive Inheritance

The X chromosome carries hundreds of genes. Males have only one X, so they express whatever allele is on it - they are hemizygous for X-linked genes. Females have two X chromosomes, so they can be carriers (heterozygous) without showing symptoms.

Key features of X-linked recessive traits:

• Affected individuals are almost always male (one bad copy is enough)
• Carrier females ($X^{A}$ $X^{a}$) are usually unaffected but can pass the allele to sons
• Affected fathers cannot pass the trait to sons (fathers give Y to sons, not X)
• All daughters of an affected father are at least carriers (they inherit his X)

Classic examples: hemophilia A, red-green color blindness, Duchenne muscular dystrophy.

X-Linked Dominant Inheritance

X-linked dominant traits are expressed in both males AND females who carry even one copy. However, because females have two X chromosomes and X-inactivation occurs randomly, affected females may show milder or more variable symptoms than affected males.

Key features:

• Affected fathers pass the trait to ALL daughters (they all get his X) but NO sons (they get Y)
• Affected mothers pass the trait to approximately half of all children regardless of sex
• Both males and females are affected, but females may show variable expressivity

Y-Linked Inheritance

The Y chromosome is small and carries very few genes (about 50-60 protein-coding genes). Y-linked traits pass exclusively from father to son.

The most important Y-linked gene is SRY (sex-determining region Y). Y-linked traits are rare and always appear in all male descendants of an affected father.

X-Inactivation and Barr Bodies

Females have twice as many X-linked genes as males. To balance gene dosage, each female cell randomly inactivates one X chromosome early in embryonic development. The inactivated X condenses into a Barr body - a dark, inactive clump visible at the edge of the nucleus.

This process is random: in some cells the maternal X is active, in others the paternal X is active. The result is a mosaic of two cell populations.

The classic example is the calico cat. Coat color is X-linked, with one allele for orange and one for black. A heterozygous female ($X^{O}$ $X^{B}$) randomly inactivates one X in each patch of skin, producing a patchwork of orange and black fur. Male cats (XY) can only be orange or black, never calico.

Pedigree Analysis

A pedigree is a family tree that tracks a trait across generations. The MCAT expects you to look at a pedigree and determine the most likely inheritance pattern.

Pedigree symbols:

• Circles = female, Squares = male
• Filled = affected, Open = unaffected
• Half-filled = carrier (for recessive traits)
• Horizontal line = mating pair
• Vertical line = parent-to-offspring connection

How to Read a Pedigree

Use this decision tree:

Step 1: Is it dominant or recessive?

• If two unaffected parents have an affected child, the trait is recessive (both parents must be carriers)
• If every affected individual has at least one affected parent, the trait is likely dominant

Step 2: Is it autosomal or X-linked?

• If affected fathers have affected sons, it is NOT X-linked (must be autosomal)
• If the trait appears much more frequently in males, consider X-linked recessive
• If an affected father passes the trait to ALL daughters, consider X-linked dominant

Quick Reference: Inheritance Pattern Clues

Mendel’s law of independent assortment works perfectly - as long as the two genes are on different chromosomes. But what happens when two genes sit on the same chromosome? They tend to be inherited together, violating independent assortment. This is called genetic linkage.

Linked Genes and Parental Types

When two genes are linked (on the same chromosome), the allele combinations inherited from each parent tend to stay together. These original combinations are called parental types.

For example, if a parent has alleles AB on one chromosome and ab on the homolog, most gametes will be either AB or ab (parental types), not Ab or aB.

If genes were truly unlinked, a dihybrid test cross (AaBb x aabb) would produce offspring in a 1:1:1:1 ratio. Linked genes deviate from this ratio - parental types are overrepresented.

Crossing Over Creates Recombinants

During prophase I of meiosis, homologous chromosomes pair up and exchange segments of DNA. This is crossing over (recombination). If a crossover event occurs between two linked genes, it separates them into new allele combinations called recombinant types.

The closer two genes are on a chromosome, the less likely crossing over will occur between them. Genes that are far apart on the same chromosome are crossed over so frequently that they behave as if they are on different chromosomes.

Recombination Frequency

Recombination frequency measures how often crossover produces recombinant offspring. It is calculated as:

Key facts about recombination frequency:

• RF = 0% means the genes are completely linked (no crossover ever separates them)
• RF = 50% means the genes assort independently (either on different chromosomes or very far apart on the same chromosome)
• RF can never exceed 50% because at most, half the gametes from a single meiosis can be recombinant

Gene Mapping

By measuring recombination frequencies between pairs of genes, you can determine their relative positions on a chromosome. This is called gene mapping.

Example: Three genes - A, B, and C - have the following RFs:

• A-B: 8 cM
• B-C: 5 cM
• A-C: 13 cM

Since 8 + 5 = 13, the order must be A - B - C, with B in the middle.

If the numbers do not add up perfectly (e.g., A-C = 12 instead of 13), the discrepancy is due to double crossovers between A and C, which can restore the parental arrangement and make the apparent distance slightly smaller than the true distance.

All genetic variation begins with mutations - changes to the DNA sequence. Some mutations are harmless. Some are lethal. A rare few are beneficial. Together, they provide the raw material for evolution and are the reason no two individuals (except identical twins) have the exact same genome.

The detailed molecular mechanisms of mutation, DNA repair, and replication are covered in the Biochemistry book (Chapters 6-7). Here we focus on the types of mutations, their consequences, and how they change the composition of a population’s gene pool - the total collection of alleles in a population.

Point Mutations

A point mutation changes a single nucleotide in the DNA sequence. There are three types:

Silent mutation: The nucleotide change does not alter the amino acid. This happens because the genetic code is degenerate - multiple codons code for the same amino acid, especially at the third (wobble) position.

Missense mutation: The change produces a different amino acid. The effect ranges from harmless (conservative substitution of a similar amino acid) to devastating. The classic example is sickle cell disease: a single A-to-T substitution changes glutamic acid to valine in hemoglobin, causing red blood cells to sickle.

Nonsense mutation: The change creates a premature stop codon, producing a truncated, usually nonfunctional protein.

Trinucleotide repeat expansion: A short DNA sequence (e.g., CAG) is repeated many extra times during replication. Each generation can add more repeats, so the disease often worsens or appears earlier (anticipation). Examples: Huntington’s disease (CAG) and fragile X syndrome (CGG).

Frameshift Mutations

Insertions or deletions of nucleotides (in numbers that are NOT multiples of 3) shift the reading frame of the mRNA. Every codon downstream of the mutation is read incorrectly, usually producing a completely nonfunctional protein.

Insertions and deletions that ARE multiples of 3 add or remove whole amino acids without disrupting the reading frame - these are non-frameshift insertions/deletions.

Chromosomal Mutations

Larger-scale changes can affect entire segments of chromosomes:

Aneuploidy - having an abnormal number of chromosomes - results from nondisjunction during meiosis. Homologous chromosomes (meiosis I) or sister chromatids (meiosis II) fail to separate properly.

Consequences of Mutations

Mutations can be:

• Neutral - no effect on fitness (most mutations fall here, especially in non-coding DNA)
• Beneficial - confer a selective advantage (e.g., heterozygous sickle cell trait protects against malaria)
• Deleterious - reduce fitness or cause disease

Germline mutations occur in eggs or sperm and are passed to offspring. Somatic mutations occur in body cells and are NOT inherited but can cause diseases like cancer in the affected individual.

Mutagens

Mutagens are environmental agents that increase mutation rates:

• Chemical mutagens: Alkylating agents, base analogs, intercalating agents (e.g., benzopyrene in cigarette smoke)
• Radiation: UV light causes thymine dimers; ionizing radiation (X-rays, gamma rays) causes double-strand breaks
• Biological mutagens: Certain viruses insert into the host genome

All carcinogens are mutagens, but not all mutagens are carcinogens. A mutagen becomes a carcinogen when it causes mutations in genes controlling cell growth (proto-oncogenes, tumor suppressors).

Changes in the Gene Pool

The gene pool is the total collection of alleles in a population. Several forces change allele frequencies over time:

Genetic Drift

Genetic drift is a random change in allele frequencies, most significant in small populations. By chance, some alleles may become more or less common - not because they are beneficial or harmful, but simply due to random sampling.

Two special cases of genetic drift:

Bottleneck effect: A catastrophic event (natural disaster, epidemic) kills a large portion of the population at random. The surviving population’s gene pool may differ dramatically from the original.

Founder effect: A small group splits off from a larger population and starts a new colony. The founders carry only a subset of the original alleles, so rare alleles may be overrepresented. This explains why some rare diseases are unusually common in certain isolated communities.

Gene Flow (Genetic Leakage)

Gene flow is the movement of alleles between populations through migration. It tends to reduce genetic differences between populations. When individuals from one population breed with another population, they introduce new alleles.

Inbreeding

Inbreeding is mating between close relatives. It does not change allele frequencies, but it increases homozygosity. This can expose harmful recessive alleles, leading to inbreeding depression - reduced fitness in a population with high levels of inbreeding.

The opposite - outbreeding (mating between unrelated individuals) - increases heterozygosity and can increase a population’s fitness.

Evolution is the change in allele frequencies in a population over time. That is it. It is not “progress” or “improvement” - it is simply that some alleles become more or less common from one generation to the next. The mechanisms that drive these changes include natural selection, genetic drift, gene flow, and mutation.

Natural Selection

Natural selection is the process by which organisms with traits better suited to their environment survive and reproduce more successfully. Over generations, the alleles responsible for those advantageous traits increase in frequency.

Four conditions are required for natural selection:

1. Variation exists in the population (different alleles for a trait)
2. The variation is heritable (genetically based, not just environmental)
3. There is a differential in reproductive success (some individuals produce more offspring)
4. The variation affects fitness (the ability to survive and reproduce in a given environment)

Fitness in evolution does not mean “strongest” or “fastest.” It means reproductive success - how many viable, fertile offspring an organism produces. A scrawny bird that raises six chicks has higher fitness than a powerful bird that raises one.

Three Types of Natural Selection

Natural selection does not always push a population in one direction. Depending on the environment, it can act in three different patterns:

Stabilizing selection favors the average phenotype and selects against extremes. The bell curve becomes narrower. Example: human birth weight - babies that are too small or too large have lower survival rates.

Directional selection favors one extreme phenotype. The bell curve shifts in one direction. Example: antibiotic resistance in bacteria - the most resistant individuals survive, shifting the population toward higher resistance.

Disruptive (diversifying) selection favors both extremes and selects against the average. The bell curve splits into two peaks. Example: beak size in certain finch populations where medium beaks are less efficient than either very large or very small beaks.

Sexual Selection

Sexual selection is selection driven by mate choice, not survival. Traits that improve reproductive access (bright plumage, antlers, courtship songs) can spread even when they make survival harder, because the fitness payoff comes from extra offspring. Peacock tails are the classic example: the tail is a metabolic burden, but it wins mates.

Two flavors show up in passages:

• Intersexual selection: one sex (usually females) chooses mates based on a trait.
• Intrasexual selection: members of one sex compete directly with each other for access to mates (e.g., males fighting for a harem).

Hardy-Weinberg Equilibrium

The Hardy-Weinberg principle describes a theoretical population where evolution is NOT occurring. It is the null hypothesis of population genetics. If a population is in Hardy-Weinberg equilibrium, allele frequencies remain constant from generation to generation.

Five conditions must be met for Hardy-Weinberg equilibrium:

1. No mutation (no new alleles being created)
2. No natural selection (all genotypes are equally fit)
3. No gene flow (no migration into or out of the population)
4. Large population (no genetic drift)
5. Random mating (no sexual selection or assortative mating)

Using Hardy-Weinberg on the MCAT

The most common MCAT application: you are given the frequency of a recessive phenotype and asked to find carrier frequency.

Example: 1 in 2,500 people has cystic fibrosis (autosomal recessive).

Step 1: $q^2 = 1/2500$, so $q = 1/50 = 0.02$

Step 2: p = 1 - q = 1 - 0.02 = 0.98

Step 3: Carrier frequency (2pq) = 2(0.98)(0.02) = 0.0392, or approximately 1 in 25 people

Speciation

Speciation is the formation of new species. It occurs when populations become reproductively isolated - they can no longer interbreed to produce viable, fertile offspring.

Speciation is closely related to polymorphism - the existence of two or more distinct phenotypes in a population. Polymorphism provides the raw variation that speciation acts upon. For example, a polymorphic population of finches with large and small beaks may eventually split into two species if the intermediate beak size is selected against.

Allopatric speciation: Geographic separation (a river, mountain range, or migration to an island) divides a population. Over time, the isolated groups accumulate genetic differences until they can no longer interbreed even if reunited.

Sympatric speciation: A new species arises within the same geographic area, without physical separation. This can occur through polyploidy (common in plants - an organism gains an extra set of chromosomes) or habitat isolation (different groups within the same area specialize in different niches).

Reproductive Isolation Mechanisms

Adaptive Radiation

Adaptive radiation occurs when a single ancestral species rapidly diversifies into many species, each adapted to a different ecological niche. The classic example is Darwin’s finches on the Galapagos Islands - a single ancestor species diversified into over a dozen species with different beak shapes suited to different food sources.

Convergent vs Divergent Evolution

Divergent evolution: a single ancestor splits into lineages that become more different over time (Darwin’s finches, mammalian forelimbs). The shared structures are homologous - same embryonic origin, different function. Human arm, whale flipper, and bat wing all use the same bone plan.

Convergent evolution: unrelated lineages independently evolve similar traits because they face similar selective pressures. The shared structures are analogous - different embryonic origin, same function. Bird wings and insect wings both fly, but evolved from completely different tissues.

Phylogenetic Trees

A phylogenetic tree diagrams evolutionary relationships. Each branch point (node) is a common ancestor; each tip is a species. Two species are most closely related when their nearest shared node is the most recent, not when their tips happen to be drawn next to each other. Rotating a branch around a node does not change the relationships.

The Molecular Clock

A molecular clock uses the rate of neutral mutations to estimate how long ago two species diverged. The more DNA differences between two species, the longer ago they shared a common ancestor. The logic: neutral mutations are not filtered by selection, so they accumulate at a roughly constant rate.

Clocks are calibrated against the fossil record. Different genes tick at different rates - highly conserved genes (e.g., ribosomal RNA) are slow clocks good for deep splits, while less constrained genes (mitochondrial DNA) tick faster and resolve recent divergences.