Chapter 3: Cell Division and Chromosome Heredity

Learning Objectives

• Review the stages of the cell cycle and analyze DNA content changes during the cycle.

• Compare mitosis and meiosis, and relate Mendel’s Laws to meiosis.

• Describe regulation of the cell cycle and consequences of dysregulation.

• Compare autosomal and sex-linked inheritance, interpret pedigrees, and explain the chromosomal theory of inheritance.

• Describe sex determination, the genes involved, and mechanisms for dosage compensation.

Importance of the Cell Cycle in Development and Cancer

Development

The cell cycle is essential for the growth and development of multicellular organisms. During embryogenesis, rapid and regulated cell divisions produce the tissues and organs of the body.

• Embryogenesis: Begins with a fertilized egg, followed by nuclear divisions, migration, and cellularization to form the blastoderm.

• Cell cycle regulation: Ensures proper timing and placement of cell divisions for normal development.

Cancer

Cancer arises when cell cycle regulation fails, leading to uncontrolled cell division and the ability of cells to invade other tissues.

• Uncontrolled cell division: Cells divide without the normal restraints.

• Metastasis: Cancer cells can colonize other parts of the body.

Mitosis Overview

The Cell Cycle

The cell cycle is the series of events that cells go through as they grow and divide. It is divided into interphase and M phase.

• Interphase: Consists of G1 (Gap 1), S (DNA synthesis), and G2 (Gap 2) phases.

• M phase: Includes mitosis (nuclear division) and cytokinesis (cytoplasmic division).

• G0 phase: A quiescent state where cells exit the cycle and do not divide.

Phases of the Cell Cycle

• G1 phase: Cell growth, active gene expression, and preparation for DNA synthesis.

• S phase: DNA replication and chromosome duplication.

• G2 phase: Preparation for cell division.

• M phase: Mitosis and cytokinesis.

Key Terms

• Chromosome: A DNA-containing structure with a centromere.

• Chromatid: One of two identical DNA duplexes after S phase; together, they are called sister chromatids.

• Centromere: The region where sister chromatids are joined and where spindle fibers attach during division.

Stages of Mitosis

• Prophase/Prometaphase: Chromosomes condense, spindle forms, nuclear envelope breaks down.

• Metaphase: Chromosomes align at the metaphase plate; cohesin holds sister chromatids together.

• Anaphase: Cohesin is cleaved, sister chromatids separate and move to opposite poles.

• Telophase: Nuclear membranes reform, chromosomes decondense.

• Cytokinesis: Cytoplasm divides, producing two daughter cells.

Chromosome and Chromatid Number Through the Cell Cycle

Control of the Cell Cycle

Checkpoints

Cell cycle checkpoints ensure that each phase is completed correctly before the next begins.

• G1 checkpoint: Checks for cell size, nutrients, and DNA damage.

• S-phase checkpoint: Ensures DNA replication is complete and accurate.

• G2 checkpoint: Verifies DNA replication and repairs before mitosis.

• Metaphase checkpoint: Ensures all chromosomes are attached to the spindle before anaphase.

Regulatory Molecules

• Cyclins: Proteins whose levels fluctuate during the cell cycle; they activate cyclin-dependent kinases (CDKs).

• CDKs: Kinases that, when activated by cyclins, phosphorylate target proteins to drive cell cycle progression.

• Proto-oncogenes: Genes that stimulate cell cycle progression; mutations can convert them to oncogenes, leading to cancer.

• Tumor suppressor genes: Genes that inhibit cell cycle progression; loss of function can result in uncontrolled division.

Meiosis and Sexual Reproduction

Overview of Meiosis

Meiosis is a specialized form of cell division that reduces the chromosome number by half, producing gametes for sexual reproduction.

• Meiosis I: Homologous chromosomes separate.

• Meiosis II: Sister chromatids separate.

• Results in four genetically distinct haploid cells.

Key Features

• Synaptonemal complex: Protein structure that holds homologous chromosomes together and facilitates recombination during prophase I.

• Crossing over: Exchange of genetic material between homologous chromosomes, increasing genetic diversity.

Meiosis and Mendel’s Laws

• Law of Segregation: Homologous chromosomes (and thus alleles) separate during meiosis I.

• Law of Independent Assortment: Different chromosome pairs assort independently during meiosis, leading to genetic variation.

Sex-Linked Inheritance and Chromosomal Theory

Autosomal vs. Sex-Linked Inheritance

• Autosomal inheritance: Traits determined by genes on non-sex chromosomes.

• Sex-linked inheritance: Traits determined by genes on sex chromosomes (X or Y).

X-Linked Inheritance

• X-linked recessive: More common in males; females must be homozygous to express the trait.

• X-linked dominant: Affects both sexes, but often more females; affected males transmit the trait to all daughters but not sons.

• Hemizygous: Males have only one X chromosome, so a single recessive allele will be expressed.

Chromosomal Theory of Inheritance

Genes are located on chromosomes, and their behavior during meiosis explains inheritance patterns. Nondisjunction (failure of chromosomes to separate) can lead to abnormal chromosome numbers and validate the chromosomal basis of inheritance.

Sex Determination and Dosage Compensation

Sex Determination Mechanisms

• Chromosomal sex: Determined by the presence or absence of specific sex chromosomes (e.g., XX vs. XY in mammals).

• SRY gene: Located on the Y chromosome; initiates male development in mammals.

• Other systems: Some species use ZW (birds, some reptiles) or X0 systems.

Dosage Compensation

Mechanisms that equalize gene expression between sexes despite differences in sex chromosome number.

• X-inactivation: In placental mammals, one X chromosome in females is randomly inactivated (Barr body) to balance gene dosage with males.

• Mosaicism: Females are mosaics for X-linked gene expression due to random X-inactivation.

Pedigree Analysis

Interpreting Pedigrees

• Determine mode of inheritance: autosomal vs. sex-linked, dominant vs. recessive.

• X-linked recessive traits often skip generations and are more common in males.

• X-linked dominant traits appear in every generation and affect both sexes.

Example: Color Blindness Pedigree

• Color blindness is X-linked recessive.

• Genotypes can be deduced based on affected/unaffected status and inheritance patterns.

• Probability calculations can determine the likelihood of offspring being affected or carriers.

Summary Table: Comparison of Mitosis and Meiosis

Key Equations

• DNA content during cell cycle:

• Probability of inheritance (for X-linked recessive):

(if mother is carrier, father is unaffected)