Cellular Reproduction and Genetics: DNA, Meiosis, and Inheritance

Posted on Feb 3, 2025 in Biology

DNA and RNA: The Building Blocks of Life

Purines (A, G) have nine atoms in a double-ring structure, while pyrimidines (T, C) have six atoms in a single ring. Adenine (A) pairs with thymine (T) via two hydrogen bonds, whereas guanine (G) pairs with cytosine (C) via three hydrogen bonds, requiring more energy to break. Complementary base pairing dictates that only purine-pyrimidine pairs fit inside the double helix. The 3′ end of a nucleic acid strand is the sugar group.

Ribonucleotides (A, G, C, U) are the monomers of RNA. Their sugar is ribose, which has an -OH group bonded to the 2′ carbon. Deoxyribonucleotides (A, G, C, T) are the monomers of DNA. They are “lacking oxygen” as they have an -H at the 2′ carbon location. Nucleotides polymerize via condensation reactions between the hydroxyl on the sugar of one nucleotide and the phosphate group on another. This forms a phosphodiester linkage, a bridge formed by the phosphate group, connecting the 3′ carbon of one nucleotide and the 5′ carbon of another. The 5′ end of a nucleic acid is an unlinked 5′ phosphate.

DNA Replication: Copying the Code

In double-stranded DNA, the backbones must run in anti-parallel directions. DNA polymerase, the enzyme that polymerizes deoxyribonucleotide monomers into DNA, catalyzes DNA synthesis. It can only add to the 3′ end of a growing chain. Replication bubbles form at specific sequences of bases called the origin of replication. Bacterial chromosomes have one origin, while eukaryotes have multiple, allowing for faster replication. Replication occurs in the 5′ to 3′ direction and is bidirectional.

DNA helicase binds to single strands of DNA, using the energy of ATP hydrolysis to separate the two strands at the replication fork. Single-strand DNA-binding proteins (SSBPs) attach to the separated strands to prevent them from snapping back into a double helix. Primase synthesizes an RNA primer. Topoisomerase relieves twisting forces by cutting the DNA, allowing it to unwind, and then rejoining it. A sliding clamp holds DNA polymerase in place.

Lagging Strand Synthesis

  1. Primer added: Primase synthesizes an RNA primer.
  2. First Okazaki fragment synthesized: DNA polymerase III synthesizes the first fragment in the 5′ to 3′ direction.
  3. Second Okazaki fragment synthesized: DNA polymerase III extends Okazaki fragments.
  4. Primer replaced: DNA polymerase I removes the ribonucleotides of the primer and replaces them with deoxyribonucleotides in the 5′ to 3′ direction.
  5. Gap closed: DNA ligase catalyzes the formation of phosphodiester bonds between the 3′ and 5′ ends of adjacent Okazaki fragments.

The sliding clamp holds DNA polymerase in place during strand extension. RNA is single-stranded, so it loops to form a double helix.

Meiosis and Mitosis: Cell Division Processes

Meiosis leads to the production of sperm and eggs, called gametes. Daughter cells are genetically different from each other and have half the amount of hereditary material as the parent cell. Mitosis leads to the production of all other cells, called somatic cells. Genetic material is copied and then divided equally between two cells during cellular respiration. Both are accompanied by cytokinesis, where the parent cell divides into two daughter cells.

The cell cycle consists of M phase and interphase. Interphase includes the S phase, where DNA replication occurs. The gap between M and S phase is the G1 phase, and G2 is between S and M. In multicellular organisms, cells perform their functional roles during the G1 phase and decide whether to begin replication and transition to the S phase. This is energetically costly, as chromosomes are replicated, and the cell enters the G2 phase. The M phase consists of the division of the nucleus and cytoplasm.

Mitosis

Mitosis divides replicated chromosomes to form two daughter nuclei.

  • Prophase: Chromosomes condense into compact structures, and the spindle apparatus begins to form from microtubule-organizing centers.
  • Prometaphase: The nuclear envelope disintegrates. Kinesin and dynein motors attached to kinetochores move chromosomes up and down microtubules.
  • Metaphase: Chromosomes line up in the middle on an imaginary plane between the two spindle poles, called the metaphase plate.
  • Anaphase: Two complete sets of daughter chromosomes are fully separated.
  • Telophase: The nuclear envelope reforms around each set of chromosomes, and they begin to de-condense.
  • Cytokinesis: The cytoplasm divides, forming two daughter cells.

Chromosome Terminology

  • Diploid: A type of chromosome with two alleles of each gene, one on each of the homologs.
  • Haploid: Organisms with one allele of each gene.
  • Ploidy: The number of chromosome sets (n, 2n, 3n, etc.). Humans are diploid (2n=46), while haploid cells/species are labeled n.
  • Chromatid: Describes the structures of replicated chromosomes.

Meiosis: Creating Genetic Diversity

Meiosis consists of two cell divisions: Meiosis I and Meiosis II.

Meiosis I

Homologs of each chromosome pair are separated. One homolog goes to one daughter cell, and the other goes to the other. At the end, each daughter cell has one of each type of chromosome instead of two, resulting in half as many chromosomes as the parent cell. A diploid (2n) parent cell produces two haploid (n) daughter cells.

  • Early Prophase I: The nuclear envelope breaks down, chromosomes condense, and the spindle apparatus begins to form. Homologous chromosome pairs come together in synapsis, resulting in a bivalent (paired homologous, replicated chromosomes, where each homolog consists of two sister chromatids).
  • Late Prophase I: The nuclear envelope is completely broken down, and each homolog in the bivalent is attached to microtubule fibers from a single spindle pole. Homologs separate at many points but stay together by X-shaped structures called chiasmata. At each chiasma, there is an exchange of parts of chromosomes between maternal and paternal homologs (crossing over).
  • Metaphase I: Kinetochore microtubules move the pairs of homologous chromosomes (bivalents) to the metaphase plate. The alignment of maternal and paternal homologs is random.
  • Anaphase I: Homologs begin moving to different poles of the spindle apparatus. Chiasmata are broken by the removal of cohesin proteins, except around the centromere.
  • Telophase I: Homologs finish moving to opposite sides of the spindle. Chromosomes in each daughter cell are a random assortment of maternal and paternal chromosomes due to crossing over and independent assortment.

Meiosis II

Meiosis II separates the sister chromatids of the replicated chromosomes into individual cells, each containing unreplicated daughter chromosomes. It is equivalent to mitosis in a haploid cell.

  • Prophase II: The spindle apparatus forms in both daughter cells. Chromosomes begin moving towards the center of the cell via microtubules attached to kinetochores.
  • Metaphase II: Chromosomes are lined up at the metaphase plate. Each chromosome is attached by spindle fibers to both spindle poles.
  • Anaphase II: Sister chromatids of each chromosome are separated.
  • Telophase II: Once separated, each chromatid is considered an independent daughter chromosome.

Meiosis vs. Mitosis

  • Homologous chromosomes do not pair during mitosis but pair early in meiosis.
  • Reduction division occurs in Meiosis I.
  • Differences in the number of cell divisions.
  • Differences in the number of chromosomes in daughter cells vs. parent cells.
  • Differences in the DNA content of daughter cells compared to parent cells.
  • Synapsis of homologs occurs in meiosis but not mitosis.
  • Meiosis promotes genetic variation.

Sexual Reproduction: Costs and Benefits

Sexual reproduction is energy-expensive, involving more cell divisions and resulting in fewer offspring. It also carries the cost of fertilization. However, it generates more genetic variation.

Mendelian Genetics: Principles of Inheritance

Discrete traits vs. continuous traits: Discrete traits are distinct, while continuous traits, like height, show a range of variation.

Principle of segregation: Starch branching enzyme example: DNA to RNA to protein to enzyme. Independent assortment: Alleles of different genes don’t stay together when gametes form. The transmission of one trait does not depend on another (dihybrid cross). Meiosis explains the principles of segregation and independent assortment. Mendel’s hereditary determinants, or genes, are located on chromosomes. Alleles for genes are shown at particular positions known as a locus.

Autosomal vs. Sex-Linked Inheritance

Autosomes: Non-sex chromosomes. Genes on non-sex chromosomes are said to be autosomal, and their patterns of inheritance are autosomal inheritance. Linkage: The tendency of alleles of particular genes to be inherited together (two or more genes located on the same chromosome). Recombinant: Possessing a new combination of alleles.

Crossing over is rare between genes that are close together but occurs more often between genes that are far apart. Genes on the same chromosome are linked and inherited together unless crossing over occurs. When crossing over occurs, the result is genetic recombination.

Genetic Terminology and Concepts

  • Homozygote: RR or rr
  • Heterozygote: Rr
  • Multiple allelism: The existence of more than two common alleles of the same gene (e.g., ABO blood type).
  • Quantitative traits: Traits greatly influenced by the environment, varying and not falling into distinct categories.

Pedigree Analysis

Autosomal recessive traits: If parents of an affected individual do not have the trait, then both parents are heterozygous carriers. When two carriers have children, 1/4 of their offspring are expected to exhibit the recessive disease phenotype.

Autosomal dominant traits: If one parent is heterozygous and the other is homozygous recessive, 1/2 of their children are expected to show the dominant phenotype.

Autosomal vs. Sex-Linked: If a trait appears about equally often in males and females, it is likely autosomal. If males express the trait more often than females, the allele is likely recessive and found on the X chromosome. Males have only one X chromosome; therefore, any X-linked allele will determine the phenotype. X-linked dominant traits are rare. An affected male passes the trait to all of his daughters and none of his sons. A heterozygous female will pass the trait to half of her daughters and half of her sons.

Gene Linkage and Recombination Frequency

Genes that are close together on the same chromosome will not be inherited together, with the frequency of coinheritance depending on the distance between the genes.

Prophase I: Crossing over allows new combinations of alleles.

Recombination frequency = # recombinants / total # of offspring. Independent assortment = 50%. Crossing over occurs more frequently when genes are farther apart. The frequency of recombinant offspring correlates directly with distance.

Advanced Genetic Concepts

  • Complete dominance: 100% penetrance (all individuals with a genotype express the phenotype).
  • Incomplete dominance: Heterozygote expresses an intermediate phenotype (e.g., red flower x white flower = pink flower).
  • Codominance: Both alleles influence the phenotype by expressing the phenotype associated with each allele (e.g., red flower x white flower = red/white flower).
  • Multiple allelism: More than two alleles (e.g., A, B, O blood type).
  • Pleiotropy: One gene affects multiple phenotypes.
  • Antagonistic pleiotropy: An allele might have negative effects but also be associated with positive effects.
  • Epistasis: When two or more genes interact to influence a phenotype.
  • Phenotypic plasticity: One genotype can produce multiple phenotypes based on environmental conditions.