12.3 Recombination and transposition

DNA recombination and transposition are crucial processes in genetic diversity and genome evolution. These mechanisms involve the exchange or movement of genetic material, reshaping genomes and creating new gene combinations.

Homologous recombination and crossing over mix up genes during meiosis, while transposable elements jump around the genome. Site-specific recombination allows precise DNA rearrangements. Together, these processes drive genetic variation and adaptation in organisms.

Homologous Recombination and Crossing Over

Mechanism and Significance of Homologous Recombination

• Homologous recombination is a process where genetic material is exchanged between two similar or identical DNA sequences
• Occurs naturally between homologous chromosomes during meiosis and is important for generating genetic diversity in offspring
• Also functions as a DNA repair mechanism by using a homologous sequence as a template to repair double-strand breaks or gaps in DNA
• Plays a crucial role in maintaining genome integrity and stability by repairing DNA damage and preventing the accumulation of deleterious mutations

Crossing Over and Holliday Junction Formation

• Crossing over is a specific type of homologous recombination that occurs during prophase I of meiosis
• Involves the physical exchange of genetic material between non-sister chromatids of homologous chromosomes
• Results in the formation of new combinations of alleles on the chromosomes, contributing to genetic variation
• During crossing over, a four-way DNA junction called a Holliday junction forms (named after Robin Holliday who proposed the model)
• Holliday junctions are created by single-strand breaks in the DNA followed by the exchange of strands between the homologous chromosomes
• Resolution of Holliday junctions by specific enzymes (resolvases) completes the crossing over process and results in the recombinant chromosomes

Importance in Meiosis and Genetic Diversity

• Homologous recombination and crossing over are essential processes in meiosis that contribute to genetic diversity in sexually reproducing organisms
• By shuffling genetic material between homologous chromosomes, these processes create new combinations of alleles in the gametes (sperm and egg cells)
• The recombinant chromosomes are then passed on to the offspring, resulting in individuals with unique genetic compositions
• Genetic diversity generated through homologous recombination and crossing over is important for evolutionary adaptability and survival of species in changing environments (disease resistance, adaptation to climate change)

Transposable Elements

Types and Characteristics of Transposons

• Transposons, also known as "jumping genes," are DNA sequences that can move from one location in the genome to another
• Transposons are classified into two main types: DNA transposons and retrotransposons
• DNA transposons move directly as DNA sequences and insert themselves into new locations in the genome
• Retrotransposons, such as long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), move through an RNA intermediate
• Retrotransposons are first transcribed into RNA, then reverse transcribed back into DNA before inserting into a new genomic location
• Transposons often contain genes encoding enzymes necessary for their own transposition (transposase for DNA transposons, reverse transcriptase for retrotransposons)

Impact on Genome Evolution and Stability

• Transposable elements are major contributors to genome evolution and play a significant role in shaping the structure and function of genomes
• Insertion of transposons into new locations can disrupt genes, alter gene expression, or create new regulatory elements
• Transposition events can lead to genomic rearrangements, such as deletions, duplications, and inversions, contributing to genome plasticity
• Accumulation of transposons over evolutionary time has resulted in a large portion of many eukaryotic genomes consisting of repetitive sequences derived from transposable elements (e.g., ~45% of the human genome)
• While transposons can contribute to genetic diversity and evolutionary innovation, their uncontrolled activity can also cause genomic instability and be associated with genetic disorders (insertional mutagenesis, chromosomal rearrangements)

Bacterial Insertion Sequences

• Insertion sequences (IS) are the simplest form of transposable elements found in bacterial genomes
• IS elements are short DNA sequences (usually 700-2500 base pairs) that encode only the transposase enzyme required for their own transposition
• IS elements are flanked by inverted repeats that serve as recognition sites for the transposase
• Insertion of IS elements can disrupt genes, alter gene expression, or promote genomic rearrangements in bacteria
• IS elements play a significant role in the evolution and adaptation of bacterial genomes, including the spread of antibiotic resistance genes (IS-mediated transfer of resistance genes between plasmids and chromosomes)

Site-Specific Recombination

Mechanism and Key Features

• Site-specific recombination is a type of recombination that occurs at specific DNA sequences, called recognition sites or target sites
• Involves the exchange of DNA strands between two specific sites, typically resulting in the integration, excision, or inversion of DNA segments
• Site-specific recombination is mediated by specialized enzymes called recombinases that recognize and bind to the specific DNA sequences
• Recombinases catalyze the cleavage and rejoining of DNA strands at the recognition sites without requiring extensive DNA synthesis or homology between the recombining sequences
• The recombination process is highly precise and does not involve the formation of Holliday junctions or the exchange of flanking sequences

Examples and Biological Significance

• Site-specific recombination plays important roles in various biological processes, such as viral integration, bacterial gene expression, and programmed DNA rearrangements
• Integration of bacteriophage lambda into the E. coli chromosome is a well-studied example of site-specific recombination
  • The lambda phage integrase (Int) recognizes specific attachment sites (att sites) on the phage and bacterial genomes
  • Int catalyzes the recombination between the phage and bacterial att sites, resulting in the integration of the phage DNA into the bacterial chromosome
• Site-specific recombination is also involved in the phase variation of bacterial surface proteins, allowing bacteria to adapt to different environments or evade host immune responses
  • In Salmonella, the inversion of a DNA segment by the Hin recombinase switches the expression of flagellar proteins, altering the bacterium's motility and virulence
• In eukaryotes, site-specific recombination is employed in programmed DNA rearrangements, such as the assembly of immunoglobulin genes in B cells (V(D)J recombination) and the mating-type switching in yeast
• Site-specific recombination systems have been harnessed as powerful tools in genetic engineering and biotechnology for precise DNA manipulation, gene targeting, and the development of gene therapy vectors (Cre-lox and FLP-FRT systems)