Mendel & Single-Gene Inheritance

General Biology: Mendel & Single-Gene Inheritance

Student Expectations Overview

Students are expected to:

• Compare and contrast blending inheritance with the segregation of alternative alleles.

• Outline the historical development of ideas about inheritance, including Mendel's contributions.

• Relate F1 and F2 generations to monohybrid and dihybrid crosses.

• Understand and apply Mendel's Law of Segregation of alternative alleles and the Law of Independent Assortment.

• Outline Mendel's experimental protocol for plant crosses.

• Define key genetic terms: gene, allele, dominance/recessive, phenotype, and genotype.

• Outline the translation of Mendel's terminology into current genetic vocabulary.

• Apply Punnett Squares to predict possible outcomes of crosses between two genotypes.

• Outline Mendel's results in the context of Punnett Squares.

• Describe human genetic disorders such as Cystic Fibrosis, Red-Green Color Blindness, Faulty Enamel Trait, and Huntington's Disease.

• Relate Mendel's results to modern human genetics.

• Outline deviations from Mendelian expectations, including incomplete dominance, codominance, multiple alleles, polygenic inheritance, and multifactorial traits.

Patterns of Inheritance: From Variation to Mechanism

Variation among individual organisms has long been observed in humans, domestic plants and animals, and wild plants and animals. Despite this variation, a consistent pattern of resemblance exists between parents and offspring.

Historical View: Blending Inheritance

For a long time, the cause or mechanism of resemblance was unknown. In the 1700s and early 1800s, the prevailing belief was blending inheritance. This theory posited that an offspring's traits were a blend or mix of its parents' traits. The consequence of this idea was that unique traits of parents would be lost forever in future generations, as they would be diluted with each successive blend.

Gregor Mendel: The Father of Modern Genetics

We now know that the idea of blending inheritance is incorrect, thanks to the pivotal work of Gregor Mendel, an Austrian monk. He is considered the "Father of modern genetics." In 1865, Mendel published his findings, describing the process we now call segregation of alternative traits. While at the monastery, he performed experiments using the common garden pea, Pisum sativum, to investigate whether different expressions of traits segregate independently of each other.

Mendel's Experimental Protocol and Findings

Mendel's experimental design was meticulous and groundbreaking. His findings, when interpreted with modern genetics and meiosis, provide the foundation for our understanding of heredity.

Experimental Steps:

1. True-breeding lines (P1 generation): Mendel first allowed plants to self-fertilize over multiple generations. This ensured that the traits of interest were transmitted consistently, producing "pure breeding" or P1 generation plants that always produced offspring with the same trait expression.

2. Hybrid offspring (F1 generation): He then removed the anthers from these true-breeding plants to prevent self-fertilization and performed specific reciprocal crosses (e.g., P x W and W x P) between plants with contrasting traits. This produced hybrid offspring, known as the F1 generation.

3. Segregation of traits (F2 generation): Mendel then permitted the F1 hybrid offspring to self-fertilize. This allowed for alternative traits to segregate and be expressed in the next generation, called the F2 generation.

4. Quantitative Analysis: Crucially, Mendel counted the number of offspring exhibiting each trait. This quantitative approach was novel and essential for identifying patterns.

Contrasting Traits and Monohybrid Crosses

Mendel used seven pairs of contrasting traits in Pisum sativum:

• Purple vs. white flower color

• Yellow vs. green seed color

• Round vs. wrinkled seed shape

• Green vs. yellow pod color

• Inflated vs. constricted pod shape

• Axial vs. terminal flower position

• Tall vs. dwarf plant height

He performed monohybrid crosses, which involved tracking a single trait (e.g., purple vs. white flowers) through successive generations.

Experimental Results: Flower Color Example

Consider a cross between a true-breeding purple-flowered plant and a true-breeding white-flowered plant:

• P1 Generation Cross: Purple Parent $imes$ White Parent

• F1 Generation: $100\%$ of the offspring had purple flowers.

  • In the F1 generation, the purple flower trait was referred to as the dominant trait, and the white flower trait as recessive.

• F2 Generation (from F1 self-fertilization): The offspring showed a mixture of traits, with $75\%$ purple flowers and $25\%$ white flowers.

  • This resulted in a phenotypic ratio of $3:1$ (dominant to recessive traits). This is known as the Mendelian ratio.

Mendelian Terminology and Modern Genetics

Key Definitions:

• Phenotype: The observable expression of a trait (what you see).

• Gene: A discrete unit of information that determines a particular trait; passed from one generation to another.

• Allele: An alternative form or expression of a gene. Individuals possess two alleles for each particular trait or gene (i.e., individuals are diploid).

• Dominance/Recessive: Describes the interaction between alleles. A dominant allele masks the expression of a recessive allele when both are present.

• Genotype: The exact allelic combination for a particular trait; the genetic makeup.

Mendel's Law of Segregation

This experiment demonstrated Mendel's Law of Segregation, which disproved the blending inheritance theory and established key principles:

1. Particulate Inheritance: Traits are passed from one generation to another as discrete informational entities, now known as genes, located on chromosomes.

2. Alleles: Expressions of traits come in alternative forms called alleles.

3. Diploidy: Every individual possesses two alleles for a particular trait (e.g., one from each parent), meaning individuals are diploid.

4. Segregation during Gamete Formation: When gametes (sex cells) form during meiosis, these two alleles segregate from each other (specifically during anaphase I). Each gamete receives only one allele for each gene.

5. Equal Probability: Each gamete has an equal probability of possessing either allele.

6. Genotype Determines Phenotype: Phenotypes (what you see) are expressions of genotypes (the exact allelic combinations).

Diagramming a Monohybrid Cross (Modern View)

Let's use modern notation for the flower color experiment:

• $P$ = allele for purple flowers (dominant)

• $p$ = allele for white flowers (recessive)

Genotypes and Phenotypes:

• $PP$ = Homozygous dominant genotype, phenotype is purple.

• $pp$ = Homozygous recessive genotype, phenotype is white.

• $Pp$ = Heterozygous genotype, phenotype is purple (due to the dominance of allele $P$ over allele $p$).

Cross from P1 to F1:

• P1 cross: $PP$ (purple) $imes$ $pp$ (white)

• F1 generation: All offspring are $Pp$, resulting in $100\%$ purple phenotype and a heterozygous genotype.

Cross from F1 to F2 (F1 self-fertilization):

• F1 cross: $Pp$ $imes$ $Pp$

• F2 generation: Individuals with genotypes $PP$, $Pp$, and $pp$ are produced.

  • Phenotype: Purple ($PP$ and $Pp$) and White ($pp$) flowered individuals.

  • Phenotypic Ratio: $3$ Purple $:$ $1$ White

  • Genotypic Ratio: $1$ $PP$ $:$ $2$ $Pp$ $:$ $1$ $pp$

Punnett Squares

Punnett Squares are a tool used to identify the possible outcomes of a cross between two genotypes. For the F1 cross ($Pp imes Pp$):

This square visually demonstrates the $1:2:1$ genotypic ratio and the $3:1$ phenotypic ratio in the F2 generation.

Mendel's Law of Independent Assortment

Mendel further investigated if different traits segregate independently of each other. The answer is yes, if the genes for those traits are not linked on the same chromosome. Mendel was fortunate to choose traits whose genes were located on different chromosomes for these experiments.

Dihybrid Cross

He performed a dihybrid cross, which involves following two traits simultaneously. Let's consider seed shape (Round vs. wrinkled) and seed color (Yellow vs. green):

• $R$ = Round (dominant), $r$ = wrinkled (recessive)

• $Y$ = Yellow (dominant), $y$ = green (recessive)

P1 Generation Cross: True-breeding Round, Yellow ($RRYY$) $imes$ True-breeding wrinkled, green ($rryy$)

F1 Generation: All offspring are heterozygous for both traits ($RrYy$). All show the dominant phenotypes: Round, Yellow.

F2 Generation (from F1 self-fertilization of $RrYy$):

• If the traits (genes) are on different chromosomes, then those chromosomes will assort independently during meiosis.

• A dihybrid cross involving individuals heterozygous for both traits ($RrYy imes RrYy$) will produce an F2 generation with a specific phenotypic ratio.

Possible Gametes from $RrYy$: $RY$, $Ry$, $rY$, $ry$ (each with equal probability).

Punnett Square for Dihybrid Cross ($RrYy imes RrYy$)

When analyzing the phenotypes from this Punnett Square, the F2 generation will express a $9:3:3:1$ phenotypic ratio:

• $9$ Round, Yellow ($R<em>Y</em>$)

• $3$ Round, green ($R_yy$)

• $3$ wrinkled, Yellow (rrY_)

• $1$ wrinkled, green ($rryy$)

This ratio demonstrates Mendel's Law of Independent Assortment, which is related to events in Metaphase I of meiosis, specifically how homologous pairs line up at the center of the cell with respect to one another.

Human Disorders and Mendelian Inheritance

Mendelian inheritance patterns (dominance-recessiveness; one gene-two alleles) explain many human genetic disorders.

Autosomal Recessive Disorders

These disorders occur when an individual inherits two copies of a recessive allele for a gene on an autosome (non-sex chromosome). Individuals with one copy are carriers but do not express the trait.

• Cystic Fibrosis (CF):

  • Most common among Caucasians in the US.

  • Caused by mutations in the CFTR (Cystic Fibrosis Transmembrane Regulator) gene on chromosome 7.

  • The CFTR protein normally acts as a channel for chloride (Cl-) ions and, in turn, impacts water movement across cell membranes. When Cl- passes through, water follows.

  • The mutant CFTR protein, often due to a deletion of three nucleotides, is non-functional, failing to pass Cl- ions.

  • Expression: Primarily in lung cells and pancreatic ducts.

  • Symptoms: Abnormally thick mucus builds up in bronchial tubes (interfering with breathing and causing infections) and pancreatic ducts (interfering with the release of digestive enzymes, which can lead to malabsorption).

  • In the lungs, the thick mucus traps bacteria and particles, leading to chronic infections. Immune responses further damage lung cells, and released DNA makes the mucus even thicker.

X-Linked Recessive Inheritance

These traits are carried on the X chromosome and are recessive. They are more frequently expressed in males because males have only one X chromosome ($XY$), so a single recessive allele on the X chromosome will be expressed. Females ($XX$) must inherit two copies of the recessive allele to express the trait.

• Hemophilia A: A blood clotting disorder.

• Duchenne Muscular Dystrophy: Leads to muscle cell atrophy.

• Red-Green Color Blindness:

  • Most frequently expressed in males.

  • Sons cannot inherit the trait from their father. Fathers pass their X chromosome to their daughters only.

  • For females to express the trait, the father must express the trait (be colorblind) AND the mother must be a carrier (heterozygous) or also express the trait.

  Example Cross (Mother Carrier $X^C X^c$ x Father Normal Vision $X^C Y$):

  	$X^C$ (from Father)	$Y$ (from Father)
  $X^C$ (from Mother)	$X^C X^C$ (Daughter, Normal)	$X^C Y$ (Son, Normal)
  $X^c$ (from Mother)	$X^C X^c$ (Daughter, Carrier)	$X^c Y$ (Son, Colorblind)

X-Linked Dominant Inheritance

These traits are carried on the X chromosome and are dominant. A single copy of the dominant allele on the X chromosome is sufficient to express the trait.

• Faulty Enamel Trait: Failure of enamel coating on teeth to develop. A heterozygous female ($X^AX^a$) will express the trait.

Autosomal Dominant Disorders

These disorders occur when an individual inherits just one copy of a dominant allele for a gene on an autosome.

• Huntington's Disorder:

  • A progressive degeneration of the nervous system, leading to poor muscle coordination and mental decline.

  • Caused by a mutation in the Huntingtin gene on chromosome 4.

  • Symptoms usually do not express until an individual is in their 40s.

  • Death typically occurs $10-15$ years after the symptoms begin.

Deviations from Mendelian Genetics

While Mendel's laws provide a fundamental framework, many traits exhibit more complex inheritance patterns.

Incomplete Dominance

• In incomplete dominance, the phenotype of the heterozygous individual is distinct from, and often intermediate to, the phenotypes of the homozygous parents.

• Example: Hair texture in humans. A homozygous parent with curly hair ($CC$) crossed with a homozygous parent with straight hair ($SS$) can produce heterozygous offspring ($CS$) with wavy hair, an intermediate phenotype.

Codominance and Multiple Alleles

• Codominance: Both alleles in a heterozygote are fully and separately expressed without blending. The phenotypes of both alleles are present simultaneously.

• Multiple Alleles: More than two alleles exist for a particular gene within a population (though an individual still only has two).

• Example: ABO Blood Types in Humans:

  • Controlled by three alleles: $I^A$, $I^B$, and $i$.

  • Dominance Hierarchy: $I^A$ is dominant over $i$ (I^A > i); $I^B$ is dominant over $i$ (I^B > i).

  • Codominance: $I^A$ and $I^B$ are codominant ($I^A = I^B$).

  • Six possible genotypes produce four phenotypes:

    • Genotypes $I^A I^A$, $I^A i$ $<br>ightarrow$ Phenotype: Type A

    • Genotypes $I^B I^B$, $I^B i$ $<br>ightarrow$ Phenotype: Type B

    • Genotype $I^A I^B$ $<br>ightarrow$ Phenotype: Type AB

    • Genotype $ii$ $<br>ightarrow$ Phenotype: Type O

• Example: Sickle-Cell Anemia:

  • Caused by codominant alleles: $Hb$ (normal hemoglobin) and $H s$ (mutant hemoglobin).

  • $Hb Hb$: Normal blood cells.

  • $H s Hs$: Severe sickle-celled blood cells, often a lethal trait.

  • $Hb Hs$: Individuals have slightly sickle-celled blood cells (sickle-cell trait). They are generally healthy but express both normal and sickle-cell hemoglobin. This is predominantly found in African Americans.

  • Reason for persistence: Heterozygotes ($Hb Hs$) with slight sickling are resistant to infection by the protozoan that causes malaria. In regions of Africa with high malaria incidence, natural selection favors heterozygotes, maintaining the $Hs$ allele in the population.

Polygenic Inheritance

• Polygenic inheritance occurs when a single trait is determined by the interaction between alleles of more than one gene.

• These traits often show continuous variation, meaning a range of variable phenotypes rather than discrete categories.

• Examples:

  • Human Height: Determined by multiple genes. The combination of alleles a person inherits (e.g., $aabbcc$, $Aabbcc$, etc.) can predict a distinct height phenotype. Within a population, this results in a continuous range of heights.

  • Skin Color: Also polygenic, influenced by many genes, leading to continuous variation in pigmentation.

Multifactorial Traits

• Multifactorial traits are phenotypes determined by interactions between one or more genes and environmental factors.

• Examples:

  • Human Height: While polygenic (multiple genes), environmental factors such as diet, nutrition, overall health, sufficient food supply, appropriate health and sanitation services, and a higher level of education also significantly contribute to how tall an individual becomes. Environmental influences can blur genetic boundaries, creating a seamless continuity across the phenotype range.

  • Clinical Depression: Research indicates that interactions between specific alleles (e.g., two copies of a serotonin allele, which influences serotonin levels in the brain) and environmental stress (e.g., four or more tumultuous events) can increase susceptibility to clinical depression. The serotonin transporter protein affects serotonin availability for signaling, and a change in this can lead to lower serotonin levels, linked to depression.