Lecture 3: The Dynamic Genome: How Genomes Change, Evolve, and Generate Diversity

Vocabulary practice flashcards covering genome dynamics, molecular evolution, repetitive elements, transposable elements, gene duplication mechanisms, genetic variation (SNPs, CNPs, GWAS), and DNA denaturation-renaturation kinetics ($$T_m$$ and $$C_0t$$ plots).

Conserved DNA Regions:

If mutated will be lost from population (natural selection)

Non-conserved DNA Regions:

Will tolerate changes based on rate of random errors → more likely to persist

Purifying Selection

An evolutionary mechanism that eliminates individuals carrying mutations that cause deleterious effects on vital cellular or developmental functions.

Point Mutation

A subtle genetic alteration involving the switch or substitution of one single nucleotide for another in a DNA sequence.

Structural Variants

Large-scale alterations of chromosome structure involving substantial segments of DNA, including deletions, duplications, inversions, insertions, and translocations.

Synteny

The conserved colocalization and order of genes on chromosomes between different species, reflecting shared evolutionary ancestry despite millions of years of divergence.

Satellite DNAs

A class of highly repetitive tandem DNA repeats consisting of $5\text{--}500\text{ bp}$ units clustered in arrays up to $100\text{ kb}$, localized predominantly at centromeres and telomeres.

Minisatellite DNAs

Tandemly repeated DNA sequences of $10\text{--}100\text{ bp}$ occurring in clusters of up to $3000$ repeats; their high inter-individual variability forms the basis for DNA fingerprinting in forensic and paternity testing.

Microsatellite DNAs

Short tandem repeat sequences consisting of $1\text{--}5\text{ bp}$ repeated in tracts of $10\text{--}40\text{ bp}$ distributed relatively evenly across genomes, frequently analyzed to compare populations.

Moderately Repeated Fraction

Genomic DNA that occupies $20\text{--}80\%$ of a genome and contains sequences repeated a few to tens of thousands of times, including protein/RNA-coding genes (such as histones and rRNAs) and non-coding interspersed elements.

LINEs

Long interspersed nuclear elements; a family of autonomous, moderately repeated retrotransposons scattered throughout the human genome.

SINEs

Short interspersed nuclear elements; a group of non-autonomous, moderately repeated retrotransposons interspersed across the genome.

Transposable Elements (TEs)

Mobile genetic elements capable of moving to new genomic sites through transposition, initially identified in maize by Barbara McClintock in 1940.

DNA Transposons

Mobile genetic elements that move by a non-replicative "cut-and-paste" mechanism mediated by a transposase enzyme, which excises the element from a donor site and integrates it into a new target site.

Inverted Repeats

Complementary, terminal DNA sequences oriented in opposite directions (approximately $20\text{ nts}$ long) that flank a transposon and are recognized by transposase during excision.

Direct Repeats

Identical target DNA sequences generated flanking both ends of an integrated transposon when staggered cuts made by transposase in the recipient DNA are filled in by DNA polymerase and ligase.

Retrotransposons

Mobile elements that transpose via a "copy-and-paste" mechanism requiring transcription into an RNA intermediate, which is then reverse-transcribed into cDNA by reverse transcriptase before insertion.

Unequal Crossing Over

An aberrant meiotic recombination event caused by the misalignment of repeated sequences on homologous chromosomes, generating a gene deletion on one chromosome and a tandem gene duplication on the other.

Pseudogene

A non-functional gene duplicate that has acquired deleterious mutations over time, inactivating its expression while the remaining functional copy preserves gene dependency.

Intragenic Mutation

A mechanism of genetic innovation wherein an existing gene sequence is modified by spontaneous point mutations or small deletions/insertions during replication or repair.

DNA Segment Shuffling

A mechanism of genetic innovation in which two or more distinct genes break and rejoin within introns, recombining modular functional exons to form novel hybrid genes (exon shuffling).

Horizontal DNA Transfer

The acquisition and integration of genetic material into an organism's genome from an unrelated organism or virus, distinct from vertical parent-to-offspring descent.

Orthologs

Genes present in different species that diverged as a result of a speciation event and originated from a single ancestral gene in the last common ancestor.

Paralogs

Homologous genes that arose via an intragenomic duplication event within a single lineage and subsequently diverged in sequence and function.

FOXP2 Gene

A gene encoding a transcription factor differing by 2 amino acids between humans and chimpanzees that is critical for oral communication and complex lip and tongue motor control.

Single Nucleotide Polymorphisms (SNPs)

Single base-pair positions in the genomic sequence that vary among individuals within a population, constituting the most frequent type of human genetic variation.

Copy Number Polymorphisms (CNPs)

Inter-individual differences in the copy number of specific DNA segments, which can cause phenotypic variation by altering protein dosage.

Genome-Wide Association Studies (GWAS)

An experimental strategy that assays hundreds of thousands of SNPs across large patient and control cohorts to identify statistical associations between specific genetic variants and complex traits or diseases.

Haplotype

A specific set of linked alleles or SNP markers located proximally on a single chromosome that tend to be inherited together as a unit across generations.

DNA Denaturation

The separation of double-stranded DNA into two single strands caused by the thermal disruption of interstrand hydrogen bonds and base-stacking interactions.

Melting Temperature ($T_m$)

The characteristic temperature at which the transition of a double-stranded DNA sample to single-stranded form is half completed ($50\%$ denatured), corresponding to the midpoint of the UV absorbance increase at $260\text{ nm}$.

Base Stacking

Non-covalent, hydrophobic, and van der Waals interactions between adjacent aromatic purine and pyrimidine rings in a DNA strand that stabilize the duplex; stacking interactions are significantly stronger between G/C pairs than A/T pairs.

DNA Renaturation

The reassociation of separated complementary single-stranded DNA molecules into a double-stranded helical duplex upon controlled cooling.

$C_0t$ Plot

A graphical representation of DNA reassociation kinetics plotting initial DNA concentration times incubation time ($C_0 \times t$) on a logarithmic scale against the fraction of renatured DNA, used to determine sequence complexity and repetition classes in a genome.