Biological Macromolecules: Nucleic Acids, Genomics, and Proteomics

Concept 5.5: Nucleic Acids Store, Transmit, and Help Express Hereditary Information

• The Programming of Polypeptides: If the primary structure of polypeptides determines a protein’s shape, the determinant of that primary structure is a discrete unit of inheritance known as a gene.

• Chemical Identity: Genes consist of $DNA$, which belongs to the class of compounds termed nucleic acids.

• Polymer Construction: Nucleic acids are polymers made of monomers called nucleotides.

• The Roles of Nucleic Acids: There are two types of nucleic acids: deoxyribonucleic acid ($DNA$) and ribonucleic acid ($RNA$). These allow living organisms to reproduce complex components between generations.

• DNA Functions:     * Provides directions for its own replication.     * Directs $RNA$ synthesis.     * Controls protein synthesis through $RNA$.

• Gene Expression: The entire process by which $DNA$ directs $RNA$ synthesis and, through $RNA$, controls protein synthesis. This is summarized as:     $DNA \rightarrow RNA \rightarrow \text{protein}$.

• Genetic Inheritance: $DNA$ is the genetic material inherited from parents. Each chromosome contains one long $DNA$ molecule, typically carrying several hundred or more genes.

• The Information/Hardware Analogy:     * $DNA$ structure encodes information that programs cell activities but is not directly involved in operations.     * $DNA$ is likened to computer software; it cannot read a barcode by itself.     * Proteins are the molecular hardware—the tools that carry out biological functions.     * Example: Hemoglobin is the protein oxygen carrier in red blood cells, not the $DNA$ that specifies its structure.

• The Role of Messenger RNA (mRNA):     * A gene along a $DNA$ molecule directs the synthesis of $mRNA$.     * $mRNA$ interacts with protein-synthesizing machinery (ribosomes) to direct the production of a polypeptide.     * In eukaryotic cells: $DNA$ resides in the nucleus, but ribosomes are in the cytoplasm (the region between the nucleus and plasma membrane). $mRNA$ conveys instructions from the nucleus to the cytoplasm.     * In prokaryotic cells: Nuclei are absent, but $mRNA$ still conveys messages from $DNA$ to ribosomes and other equipment.

The Components of Nucleic Acids

• Polynucleotides: Nucleic acids exist as polymers called polynucleotides.

• Nucleotide Structure: Composed of three specific parts:     1. A five-carbon sugar (a pentose).     2. A nitrogen-containing (nitrogenous) base.     3. One to three phosphate groups.

• Monomer vs. Polymer State: The beginning monomer used to build a polynucleotide has $3$ phosphate groups, but $2$ are lost during polymerization.

• Nucleoside: The portion of a nucleotide without any phosphate groups (Base + Sugar).

• Nitrogenous Bases:     * Rings include nitrogen atoms that take up $H^+$ from solution, thus acting as bases.     * Pyrimidines: Feature one six-membered ring of carbon and nitrogen atoms. Members include:         * Cytosine ($C$)         * Thymine ($T$) — found only in $DNA$.         * Uracil ($U$) — found only in $RNA$.     * Purines: Larger than pyrimidines, featuring a six-membered ring fused to a five-membered ring. Members include:         * Adenine ($A$)         * Guanine ($G$)

• Pentose Sugars:     * Deoxyribose: Found in $DNA$. It lacks an oxygen atom on the second carbon in the ring.     * Ribose: Found in $RNA$.     * Numbering: Carbon numbers in the sugar involve the prime symbol ($'$); the phosphate group attaches to the $5'$ carbon.

Nucleotide Polymers

• Polymerization Process: Nucleotides link into polynucleotides via a dehydration reaction.

• Phosphodiester Linkage: Adjacent nucleotides are joined by a phosphate group that links the sugars of two nucleotides.

• Sugar-Phosphate Backbone: The repeating pattern of sugar-phosphate units. Nitrogenous bases are not part of the backbone.

• Directionality: A polynucleotide has a built-in directionality refered to as $5' \rightarrow 3'$.     * The $5'$ end has a phosphate attached to a $5' \text{ carbon}$.     * The $3'$ end has a hydroxyl group on a $3' \text{ carbon}$.

• Information Encoding: Specific information is carried in the linear sequence of bases. Because genes are hundreds to thousands of nucleotides long, base sequence possibilities are effectively limitless.     * Example: Sequence $5'-AGGTAACTT-3'$ has a different meaning than $5'-CGCTTTAAC-3'$.

The Structures of DNA and RNA Molecules

• DNA Double Helix:     * Consists of two polynucleotide “strands” winding around an imaginary axis.     * Antiparallel Arrangement: The two sugar-phosphate backbones run in opposite $5' \rightarrow 3'$ directions, similar to a divided highway.     * Interior/Exterior: Backbones are on the outside; nitrogenous bases are paired in the interior.     * Bonding: Hydrogen bonds between paired bases hold the strands together.

• Base Pairing Rules in DNA:     * Adenine ($A$) always pairs with Thymine ($T$).     * Guanine ($G$) always pairs with Cytosine ($C$).     * Complementarity: The strands are predictable counterparts. If one strand is $5'-AGGTCCG-3'$, the other must be $3'-TCCAGGC-5'$.     * This feature allows the generation of two identical copies of $DNA$ for cell division.

• RNA Structure:     * Usually exists as single strands.     * Versatility: Base pairing can occur between regions of two $RNA$ molecules or within the same molecule, allowing specific $3\text{-}D$ shapes.     * Transfer RNA (tRNA): Roughly $80 \text{ nucleotides}$ in length; functional $L\text{-shape}$ resulting from base pairing of antiparallel stretches.     * Base Pairing in RNA: Adenine ($A$) pairs with Uracil ($U$); Thymine ($T$) is absent.

Concept 5.6: Genomics and Proteomics Transform Biological Inquiry

• Historical Context:     * $1953$: Description of $DNA$ structure.     * $1970s$: Development of first chemical techniques for $DNA$ sequencing.     * $1990\text{--}early 2000s$: The Human Genome Project sequenced all $3 \text{ billion}$ bases of the human genome.

• Technological Advances:     * Cost of sequencing $1 \text{ million}$ bases decreased from over $\$5,000$ in $2001$ to less than $\$0.02$ in $2016$.     * Bioinformatics: The use of computer software and computational tools to analyze large data sets.

• Analytical Approaches:     * Genomics: Analyzing large sets of genes or whole genomes of different species.     * Proteomics: Analysis of large sets of proteins and their sequences.

• Applications of Genomics and Proteomics:     * Evolution: Identifying relationships; e.g., the hippopotamus is identified as the land mammal most closely related to whales.     * Conservation Biology: Identifying species killed illegally (e.g., tracking elephant tusk poachers).     * Paleontology: Sequencing ancient tissues from Neanderthals ($Homo neanderthalensis$).     * Medical Science: Identifying genetic bases for diseases like cancer to allow “personalized medicine.”     * Species Interactions: Characterizing plant-associated communities of fungi and bacteria to improve agriculture.

DNA and Proteins as Tape Measures of Evolution

• Molecular Genealogy: Linear sequences of nucleotides are passed from parents to offspring, determining protein amino acid sequences. Siblings have higher similarity than unrelated individuals.

• Species Comparison: Closely related species share a greater proportion of $DNA$ and protein sequences.

• Hemoglobin Comparisons ($\beta \text{ polypeptide chain}$):     * Total length: $146 \text{ amino acids}$.     * Humans and gorillas differ by $1 \text{ amino acid}$.     * Humans and frogs differ by $67 \text{ amino acids}$.

• Genome Percentage Comparisons:     * Human vs. Chimpanzee: $95\text{--}98\%$ identical.     * Human vs. Mouse: roughly $85\%$ identical.

Problem-Solving and Scientific Skills Exercises

• Fish Fraud Investigation:     * Pacific salmon (Oncorhynchus) vs. Farmed Atlantic salmon (Salmo salar).     * Standard Sequence for O. kisutch (Coho salmon): $5'-AGGCACCGCCCTAAGTCTAC-3'$.     * Standard Sequence for O. keta (Chum salmon): $5'-AGGCACCGCCCTGAGCCTAC-3'$.     * Standard Sequence for S. salar (Atlantic salmon): $5'-CGGCACCGCCCTAAGTCTCT-3'$.     * Sample labeled as O. kisutch sequence: $5'-CGGCACCGCCCTAAGTCTCT-3'$.     * Conclusion: The sample matches S. salar ($100\%$ identity), indicating fraud.

• Beta-globin Analysis (Human, Monkey, Gibbon):     * Researchers isolate polypeptides or sequence $DNA$ to deduce amino acid order.     * Sequence data for $146 \text{ amino acids}$ is aligned to find mismatches.     * Comparison reveals whether the rhesus monkey or gibbon is more closely related based on common residues with the human sequence.

Summary of Key Biological Macromolecules

• Carbohydrates (Concept 5.2): Monosaccharide monomers (e.g., glucose). Polysaccharides include starch (energy storage in plants), glycogen (energy storage in animals), cellulose (plant cell walls), and chitin (exoskeletons).

• Lipids (Concept 5.3): Hydrophobic; not true polymers. Triacylglycerols (fats/oils) consist of glycerol and $3$ fatty acids. Phospholipids consist of glycerol, $2$ fatty acids, and a phosphate group (form bilayers). Steroids consist of $4$ fused rings (e.g., cholesterol, hormones).

• Proteins (Concept 5.4): Amino acid monomers ($20$ types). Functions include catalysis (enzymes), defense, storage, transport, hormonal signaling, receptors, movement, and structural support.

• Nucleic Acids (Concept 5.5): Nucleotide monomers. $DNA$ stores hereditary info; $RNA$ functions in gene expression and carrying instructions from $DNA$ to ribosomes.