BBS1001 Lecture 7: DNA Variation in Individuals and Populations, Part I - Mutations, Molecular Clock and Phylogenetic Trees

Comprehensive practice flashcards in vocabulary style covering BBS1001 Lecture 7 (DNA variation, mutation mechanisms, molecular evolution, molecular clock, and phylogenetic reconstruction via UPGMA and maximum parsimony).

Dr. Roger Godschalk

The lecturer for BBS1001 Lecture 7; a genetic toxicologist based in the Department of Pharmacology & Toxicology at Maastricht University.

BBS1001

The foundational biomedical sciences course featuring Lecture 7 on DNA variation in individuals and populations.

BBS1005

A subsequent biomedical sciences course in the curriculum that covers DNA repair mechanisms in detail.

Lars Eijssen

The lecturer who leads the alignment lecture/workshop covering pairwise alignment algorithms and scoring systems.

Macromolecule-to-Population Continuum

The overarching BBS1001 storyline progressing from biological macromolecules ("Lego bricks of life") to organelles, cells, tissues, organs, individuals, and populations.

Lecture 7 Mutation Arrow

The new conceptual arrow introduced in Lecture 7 linking DNA-level macromolecular changes directly to individuals and populations.

Mutagenesis (Lecture Outline Block 1)

The first major section of Lecture 7, addressing the definition of mutations, their classifications, and their biological effects.

Molecular Evolution (Lecture Outline Block 2)

The second major section of Lecture 7, examining sequence alignment, substitution rates, rate variation across genomes, and the molecular clock.

Molecular Phylogenetics (Lecture Outline Block 3)

The third major section of Lecture 7, focusing on rooted and unrooted trees and reconstruction methods including UPGMA and maximum parsimony.

Whisper Error: Roger Goertschalek

A Whisper speech-recognition transcription error for the lecturer's name, Dr. Roger Godschalk.

Whisper Error: cytogram C

A Whisper speech-recognition transcription error for the mitochondrial respiratory chain protein cytochrome c.

Whisper Error: deep purination

A Whisper speech-recognition transcription error for depurination, the spontaneous hydrolysis of purine bases from DNA.

Whisper Error: nullizomy

A Whisper speech-recognition transcription error for nullisomy ($2N - 2$), the numerical loss of a homologous chromosome pair.

Whisper Error: space substitutions

A Whisper speech-recognition transcription error occurring in the closing summary for base substitutions.

Whisper Error: Leusin

A Whisper speech-recognition transcription error for the amino acid leucine.

Whisper Error: sparsimony

A Whisper speech-recognition transcription error for maximum parsimony, the character-based tree-building method.

Whisper Error: NPPGMA / BGMA / DGMA

Whisper speech-recognition transcription errors occurring during the Q&A for the UPGMA clustering algorithm.

Lecturer Slip: MHC as an Enzyme

A verbal slip by the lecturer referring to MHC as an enzyme, whereas MHC proteins are antigen-presenting immune-system molecules.

Lecturer Slip: Intrachromosomal Translocation

A verbal slip where the lecturer said "intrachromosomal" twice while describing translocations occurring between non-homologous chromosomes.

Lecturer Slip: Alignment Length

The lecturer's verbal statement citing "three mutations in … 20 base pairs," whereas the slide alignment contains exactly $28\text{ columns}$.

Mutation

A heritable change in the genetic information, transferred from parent to offspring or from a dividing cell to its daughter cells.

Broad Heritability

The transmission of genetic modifications not only across organismal generations but also from a mother cell to its two daughter cells during mitosis.

1950s DNA Stability Hypothesis

The historical post-double-helix misconception that DNA is an entirely stable, static macromolecule serving as the "library of the cell."

Dynamic DNA Reality

The biological fact that DNA is constantly damaged by endogenous and exogenous forces, continuously repaired, and subject to mutation accumulation.

Gene Mutation

A molecular mutation restricted to a single gene locus, including point mutations, base substitutions, and small indels.

Chromosomal Mutation

A large-scale genetic alteration involving the structural reorganization or numerical variation of whole chromosomes.

Somatic Cells

All non-germline body cells (e.g., skin, lung, brain, heart) whose genetic changes affect only the individual organism.

Somatic Mutation

A mutation arising in non-germline body tissues; it is replicated into clonal daughter cells but cannot be transmitted to offspring.

Germ Cells

Specialized reproductive cells (spermatozoa and oocytes) that produce haploid gametes for sexual reproduction.

Germline Mutation

A mutation occurring in reproductive germ cells that can be passed to subsequent organismal generations.

Phylogenetic Data Source

Germline mutations, which persist and accumulate along ancestral reproductive lineages, unlike transient somatic mutations.

Inherited Genetic Disease Origin

Exclusively germline mutations, because mutations occurring in somatic organs like the lung cannot be passed to progeny.

Rapidly Dividing Tissues

Tissues undergoing continuous, frequent cell divisions (e.g., skin and gut epithelium) that accumulate higher mutation counts due to replication errors.

Point Mutation Chance

The compound probability of a base substitution per site per replication, measured at $10^{-10}$.

Mutations per Genome Replication

Approximately $0.3$ mutations accumulated per single replication of a haploid human genome ($3 \times 10^9\text{ bp} \times 10^{-10}$).

Phenotypic Variation Engine

Mutation, which generates the primary diversity upon which natural selection acts.

Unfavourable Mutations

Mutational changes that reduce organismal fitness or survivability and are selectively eliminated from a population.

Favourable Mutations

Beneficial mutational changes that enhance organismal survival and reproductive success, increasing in population frequency.

Morphological Phylogenetics

Classical evolutionary tree reconstruction based on macroscopic phenotypic characteristics, such as limb counts or skeletal morphology.

Sequence-Based Phylogenetics

Modern evolutionary tree reconstruction using aligned DNA or protein sequences to determine split times and branching topologies.

Purines

Double-ring nitrogenous bases found in DNA and RNA, specifically adenine ($A$) and guanine ($G$).

Pyrimidines

Single-ring nitrogenous bases found in DNA, specifically cytosine ($C$) and thymine ($T$).

Adenine ($A$)

A purine base that forms two hydrogen bonds with the pyrimidine thymine in double-stranded DNA.

Guanine ($G$)

A purine base that forms three hydrogen bonds with the pyrimidine cytosine in double-stranded DNA.

Cytosine ($C$)

A pyrimidine base that forms three hydrogen bonds with the purine guanine in double-stranded DNA.

Thymine ($T$)

A pyrimidine base that forms two hydrogen bonds with the purine adenine in double-stranded DNA.

Base Substitution

A point mutation wherein a single base pair in a DNA duplex is replaced by a different base pair.

Transition

A base substitution occurring within the same chemical ring family: purine to purine ($A \leftrightarrow G$) or pyrimidine to pyrimidine ($C \leftrightarrow T$).

Transversion

A base substitution occurring between different chemical ring families: purine to pyrimidine or pyrimidine to purine.

Number of Transition Types

Exactly $2$ distinct substitution classes: $A \leftrightarrow G$ and $C \leftrightarrow T$.

Number of Transversion Types

Exactly $4$ distinct substitution classes: $A \leftrightarrow C$, $A \leftrightarrow T$, $G \leftrightarrow C$, and $G \leftrightarrow T$.

Purine Transition

An intra-class base substitution exchanging adenine and guanine ($A \leftrightarrow G$).

Pyrimidine Transition

An intra-class base substitution exchanging cytosine and thymine ($C \leftrightarrow T$).

Transversion Pathway $A \leftrightarrow C$

An inter-class substitution replacing the purine adenine with the pyrimidine cytosine, or vice versa.

Transversion Pathway $A \leftrightarrow T$

An inter-class substitution replacing the purine adenine with the pyrimidine thymine, or vice versa.

Transversion Pathway $G \leftrightarrow C$

An inter-class substitution replacing the purine guanine with the pyrimidine cytosine, or vice versa.

Transversion Pathway $G \leftrightarrow T$

An inter-class substitution replacing the purine guanine with the pyrimidine thymine, or vice versa.

Lecturer's Transversion Mnemonic

The memory trick: "if I go from one type of base to a different type of base, the version of my base changes → trans-version."

Slide 6a Example ($AT \rightarrow GC$)

A transition mutation occurring via an $A \rightarrow G$ change in the purine-containing base pair.

Slide 6b Example ($CG \rightarrow GC$)

A transversion mutation occurring via a $C \rightarrow G$ pyrimidine-to-purine change.

Reference Reading Sequence (Russell)

The top-strand 5'→3' mRNA sequence TCT CAA AAA TTT ACG translating to Ser–Gln–Lys–Phe–Thr.

Codon AAA

The wild-type codon in the third position of the Russell slide example, encoding the amino acid lysine (Lys).

Missense Mutation

A base substitution that alters a codon such that it directs the incorporation of a different amino acid.

Slide Missense Example ($AAA \rightarrow GAA$)

A first-position $AT \rightarrow GC$ transition converting lysine (Lys) to glutamic acid (Glu).

Codon GAA

An acidic amino-acid codon specifying glutamic acid (Glu), produced by a missense transition in codon AAA.

Nonsense Mutation

A base substitution that changes an amino-acid-specifying codon into a translation termination (stop) codon.

Slide Nonsense Example ($AAA \rightarrow UAA$)

A first-position $AT \rightarrow TA$ transversion converting lysine (Lys) into an ochre stop codon (UAA).

Stop Codon UAA

A triplet termination codon that arrests ribosomal polypeptide elongation, truncating the resulting protein.

Truncated Protein

A prematurely shortened polypeptide produced by a nonsense mutation, typically rendering the protein non-functional.

Stop Codon UAG

One of the three standard genetic stop codons (amber) that signals the termination of mRNA translation.

Stop Codon UGA

One of the three standard genetic stop codons (opal) that halts ribosomal translation.

Start Codon AUG

The universal initiation codon that establishes the reading frame and encodes methionine (Met).

Non-stop Mutation

A base substitution converting a normal termination codon into an amino-acid codon, causing continuous translational readthrough.

Neutral Mutation

A missense substitution changing an amino acid to one with similar physicochemical properties, preserving protein folding and function.

Slide Neutral Example ($AAA \rightarrow AGA$)

A second-position $AT \rightarrow GC$ transition replacing lysine (Lys) with the similarly charged basic residue arginine (Arg).

Codon AGA

A basic amino-acid codon specifying arginine (Arg), produced by a neutral mutation of lysine codon AAA.

Silent Mutation

A base substitution that alters a codon but does not change the encoded amino acid due to genetic code degeneracy.

Slide Silent Example ($AAA \rightarrow AAG$)

A third-position $AT \rightarrow GC$ transition converting AAA to AAG, both of which code for lysine (Lys).

Codon AAG

A synonymous codon for lysine (Lys) resulting from a third-position silent transition in codon AAA.

Degeneracy of the Genetic Code

The feature of the genetic code wherein multiple distinct triplet codons specify the same single amino acid.

Third Codon Position

The wobble base position of a codon where base substitutions most frequently result in silent mutations.

Protein-Preserving Mutations

Neutral and silent mutations, both of which allow the encoded protein to retain its biochemical activity.

Phenotypic Difference Between Neutral and Silent Mutations

A neutral mutation alters the amino-acid residue to a chemically similar one; a silent mutation leaves the amino-acid residue identical.

Promoter Mutation

A mutation in a gene's regulatory region that alters the binding affinity of transcription factors or RNA polymerase.

Transcription-Down Promoter Mutation

A promoter alteration preventing transcription factors or RNA polymerase from binding, abolishing or reducing gene expression.

Transcription-Up Promoter Mutation

A promoter alteration enhancing polymerase or transcription-factor binding, increasing transcriptional frequency.

Splice-Site Mutation

A mutation occurring at conserved intron-exon junctions that disrupts proper pre-mRNA splicing.

Intron Retention

The failure to excise an intervening intron during pre-mRNA processing due to a mutated splice junction, yielding a non-functional protein.

Exon Skipping

The erroneous excision of a coding exon during splicing caused by the loss of boundary recognition sequences.

Non-Coding Phenotypic Mutation

A mutation in a non-coding functional region (such as a promoter or splice site) that alters the organismal phenotype without altering coding exons.

Insertion

A mutation characterized by the addition of one or more extra nucleotide pairs into a DNA sequence.

Deletion

A mutation characterized by the removal of one or more nucleotide pairs from a DNA sequence.

Indel

An operational term for an insertion/deletion event when the ancestral sequence state is unknown between two compared species.

Frameshift Mutation

An insertion or deletion of a number of base pairs that is not an exact multiple of $3$, shifting the downstream translational reading frame.

In-Frame Mutation

An insertion or deletion of base pairs in an exact multiple of $3$, adding or deleting intact amino acids without altering downstream codons.

Frameshift Downstream Consequence

The complete scrambling of the downstream amino-acid sequence, typically terminating in a premature nonsense stop codon.

Slide 9 GC Insertion Example

An insertion of a GC pair after the Gln codon that scrambles Ser–Gln–Lys–Phe–Thr into Ser–Gln–Glu–Ile–Tyr.

Slide 10 In-Frame Insertion

The addition of a 3-base segment ($+3\text{ bases}$) that inserts a single extra amino acid into the polypeptide (Pro–X–Glu–Glu–Lys).

Slide 10 $\beta$-Globin Frameshift

An insertion altering the normal $\beta$-globin sequence Pro–Glu–Glu–Lys into the scrambled frameshifted peptide Pro–Arg–Gly–Glu.

Whole-Gene Deletion

A large-scale deletion that removes an entire gene locus, preventing the production of any gene product.