Overview
This lecture covers general features of the human genome, emphasizing non-genic and repetitive DNA sequences, genome structure, sequence variation, DNA repair mechanisms, and how mutations arise and are inherited.
Structure and Composition of the Human Genome
- The human genome includes nuclear DNA (46 chromosomes) and mitochondrial DNA.
- Genes are only a small portion (~20%) of the genome; most DNA does not encode proteins.
- Coding sequences (exons) make up about 2% of the genome; the rest are introns and non-coding regions.
- Humans are diploid, inheriting one set of 23 chromosomes from each parent.
Types and Functions of DNA Sequences
- Extragenic DNA includes regulatory sequences, pseudogenes, and repetitive DNA.
- Repetitive DNA is half of the human genome and consists of tandem repeats (satellites, minisatellites, microsatellites) and dispersed repeats (transposons, retrotransposons).
- Tandem repeats have structural roles (e.g., centromeres, telomeres); minisatellites/microsatellites are highly polymorphic and used in genetic fingerprinting.
- Dispersed repeats include inactive transposons and retrotransposons, often remnants of ancient viral infections.
Genome Size, Complexity, and Evolution
- Genome size does not correlate with organismal complexity.
- Humans have about 20,000-25,000 protein-coding genes, similar to simpler organisms.
- Complexity arises from gene regulation and alternative splicing, not gene number.
- The human genome has been fully sequenced; reference sequences assist in analysis.
Genetic Variation and DNA Fingerprinting
- Minisatellites and microsatellites vary in repeat number between individuals (polymorphisms).
- These variations are used in forensic genetics and paternity tests via techniques like PCR and electrophoresis.
- Each individual’s pattern of repeats is unique (genetic fingerprint).
DNA Mutation and Inheritance
- Mutations are permanent DNA sequence changes; can be neutral, deleterious, or beneficial.
- Mutations may be small (micromutations) or large (macromutations/chromosomal aberrations).
- Mutations in gametes are inheritable; mutations in somatic cells are not.
DNA Repair Mechanisms
- Errors during replication are corrected by DNA polymerase proofreading and mismatch repair.
- Spontaneous damage (depurination, deamination) is repaired by base excision repair.
- UV light and chemicals can cause bulkier lesions, repaired by nucleotide excision repair.
- Double-strand breaks are repaired by non-homologous end-joining (error-prone) or homologous recombination (accurate).
- Defects in repair genes increase cancer risk.
Key Terms & Definitions
- Exon — Coding DNA sequence within a gene.
- Intron — Non-coding DNA sequence within a gene.
- Tandem Repeats (Satellites, Minisatellites, Microsatellites) — DNA repeat blocks in sequence, important for structure or genetic identification.
- Transposon/Retrotransposon — DNA elements capable of moving to new locations in the genome.
- Polymorphism — Genetic variation present in >1% of the population.
- Mutation — Permanent change in DNA sequence.
- Mosaicism — Presence of genetically distinct cell populations in one individual.
- DNA fingerprint — Unique pattern of DNA repeats used for identification.
- Proofreading — DNA polymerase function correcting errors during replication.
Action Items / Next Steps
- Review DNA repair mechanisms and mutation types for the next class.
- Prepare for upcoming coverage of genome sequencing techniques (Sanger sequencing).
- Complete any assignments or readings on general genome organization and DNA polymorphisms.