Lecture 6 - Recombination of DNA PDF

MICROBIAL GENETICS Lecture 6 Recombination of DNA Prepared by: Dr. Abeer Aloufi Assistant professor in Microbiology Lecture 6 - Recombination of DNA ▪ Genetic recombination refers to the rearrangement of DNA sequences by the breakage and rejoining of chromosomes or chromosome segments ▪ It also...

MICROBIAL GENETICS Lecture 6 Recombination of DNA Prepared by: Dr. Abeer Aloufi Assistant professor in Microbiology Lecture 6 - Recombination of DNA ▪ Genetic recombination refers to the rearrangement of DNA sequences by the breakage and rejoining of chromosomes or chromosome segments ▪ It also describes the consequences of such rearrangements, that is, the inheritance of novel combinations of alleles in the offspring that carry recombinant chromosomes ▪ Because the frequency of recombination is approximately proportional to the physical distance between markers, it provides the basis for genetic mapping ▪ Recombination also serves as a mechanism to repair some types of potentially lethal damage to chromosomes Lecture 6 - Recombination of DNA In Bacteria: ▪ Bacterial recombination is a common feature of gene transfer between bacteria, is the requirement for the transferred piece of DNA to be inserted into the recipient chromosome by breaking both DNA molecules, crossing them over, and rejoining them ▪ There are three methods of genetic recombination that are utilized by bacteria, they are transformation, transduction, and conjugation ▪ This recombination process creates genetic diversity at the level of genes that reflects differences in the DNA sequences of different Bacteria Lecture 6 - Recombination of DNA In Bacteria: Lecture 6 - Recombination of DNA In Eukaryotic: ▪ Genetic recombination is of fundamental importance for a wide variety of biological processes in eukaryotic cells ▪ One of the major questions in recombination relates to the mechanism by which the exchange of genetic information is initiated ▪ In recent years, DNA double-strand breaks (DSBs) have emerged as an important lesion that can initiate and stimulate meiotic and mitotic homologous recombination, they are described in this review article (Meiotic versus mitotic recombination: Two different routes for double-strand break repair) Lecture 6 - Recombination of DNA In Eukaryotic: ▪ The models by which DSBs induce recombination, describe the types of recombination events that DSBs stimulate, and compare the genetic control of DSB-induced mitotic recombination in budding and fission yeasts was examined in this review article (Double-Strand BreakInduced Recombination in Eukaryotes) Lecture 6 - Recombination of DNA In Eukaryotic: BioEssays, Volume: 32, Issue: 12, Pages: 1058-1066, First published: 21 October 2010, DOI: (10.1002/bies.201000087) Lecture 6 - Recombination of DNA In Viruses: ▪ Genetic recombination of viruses is the process by which genetic material (either DNA or RNA) is exchanged between parental viral genomes ▪ The outcome of genetic recombination is a new genetic entity that carries genetic information in non-parental combinations ▪ Biochemically, recombination is a process of combining or substituting portions of nucleic acid molecules Lecture 6 - Recombination of DNA In Viruses: ▪ Recombination has been recognized as an important process leading to the genetic diversity of viral genomes upon which natural selection can function ▪ Depending on the category of viruses, recombination can occur at the RNA or DNA levels ▪ Since these processes are different for DNA and RNA viruses, they are described in this review article (Recombination) Lecture 6 - Recombination of DNA In Viruses: ▪ Recombination involves the exchange of genetic material between two related viruses during the coinfection of a host cell ▪ Recombination by Independent Assortment ▪ Recombination by independent assortment can occur among viruses with segmented genomes ▪ Genes that reside on different pieces of nucleic acid are randomly assorted Lecture 6 - Recombination of DNA In Viruses: ▪ This can result in the generation of viruses with new antigenic determinants and new host ranges ▪ The development of viruses with new antigenic determinants through independent assortment is called antigenic shift Lecture 6 - Recombination of DNA In Viruses: Lecture 6 - Recombination of DNA Types and Examples of Recombination: ▪ Four types of naturally occurring recombination have been identified in living organisms: 1- General or homologous recombination 2- Illegitimate or nonhomologous recombination 3- Site-specific recombination 4- Replicative recombination Lecture 6 - Recombination of DNA Types and Examples of Recombination: General or homologous recombination (Holliday Model) ▪ In general recombination (also known as homologous recombination), is the genetic exchange that takes place between a pair of homologous DNA sequences ▪ These are usually located on two copies of the same chromosome, although other types of DNA molecules that share the same nucleotide sequence can also participate ▪ The general recombination reaction is essential for every proliferating cell because accidents occur during nearly every round of DNA replication that interrupt the replication fork and require general recombination mechanisms to repair Lecture 6 - Recombination of DNA Types and Examples of Recombination: General or homologous recombination (Holliday Model) ▪ The details of the intimate interplay between replication and recombination are still incompletely understood, but they include using variations of the homologous end-joining reaction to restart replication forks that have run into a break in the parental DNA template ▪ It occurs between DNA molecules of very similar sequences, such as homologous chromosomes in diploid organisms, using one or a small number of common enzymatic pathways Lecture 6 - Recombination of DNA Types and Examples of Recombination: General or homologous recombination (Holliday Model) Homologous or general recombination, each homologous chromosome is shown as a different shade of blue and a distinctive thickness, with different alleles for each of the three genes on each Recombination between genes A and B leads to a reciprocal exchange of genetic information, changing the arrangement of alleles on the chromosomes Lecture 6 - Recombination of DNA Types and Examples of Recombination: General or homologous recombination (Holliday Model) Lecture 6 - Recombination of DNA Types and Examples of Recombination: Illegitimate or nonhomologous ▪ Occurs in regions where no large-scale sequence similarity is apparent, e.g. translocations between different chromosomes or deletions that remove several genes along a chromosome ▪ However, when the DNA sequence at the breakpoints for these events is analyzed, short regions of sequence similarity are found in some cases ▪ For instance, recombination between two similar genes that are several million bp apart can lead to the deletion of the intervening genes in somatic cells Lecture 6 - Recombination of DNA Types and Examples of Recombination: Illegitimate or nonhomologous Nonhomologous (or illegitimate) recombination, two different chromosomes (denoted by the different colors and different genes) recombine, moving, e.g. gene C so that it is now on the same chromosome as genes D and E Although the sequences of the two chromosomes differ for most of their lengths, the segments at the sites of recombination may be related, denoted by the yellow and orange rectangles Lecture 6 - Recombination of DNA Types and Examples of Recombination: Illegitimate or nonhomologous Lecture 6 - Recombination of DNA Types and Examples of Recombination: Two types of recombination are typically distinguished: Homologous recombination, where a fragment of a genome is replaced by the corresponding sequence from another genome, and nonhomologous recombination, which causes genetic additions of new material and is also called lateral gene transfer (LGT) Lecture 6 - Recombination of DNA Types and Examples of Recombination: Site-specific recombination ▪ Occurs between particular short sequences (about 12 to 24 bp) present on otherwise dissimilar parental molecules ▪ Site-specific recombination requires a special enzymatic machinery, basically one enzyme or enzyme system for each particular site ▪ Good examples are the systems for integration of some bacteriophage, such as λ, into a bacterial chromosome and the rearrangement of immunoglobulin genes in vertebrate Lecture 6 - Recombination of DNA Types and Examples of Recombination: Site-specific recombination Site-specific recombination leads to the combination of two different DNA molecules, illustrated here for a bacteriophage l integrating into the E. coli chromosome Lecture 6 - Recombination of DNA Types and Examples of Recombination: Site-specific recombination Lecture 6 - Recombination of DNA Types and Examples of Recombination: What is the difference between homologous and site-specific recombination? Homologous recombination occurs between DNA with extensive sequence homology anywhere within the homology Site-specific recombination occurs between DNA with no extensive homology (although very short regions may be critical) only at special sites Lecture 6 - Recombination of DNA Types and Examples of Recombination: Replicative recombination ▪ Generates a new copy of a segment of DNA ▪ Many transposable elements use a process of replicative recombination to generate a new copy of the transposable element at a new location Lecture 6 - Recombination of DNA Types and Examples of Recombination: Replicative recombination This reaction is catalyzed by a specific enzyme that recognizes a short sequence present in the target site in the bacterial chromosome, called Replicative recombination is seen for some transposable elements, shown as red rectangles, again using a specific enzyme, in this case encoded by the transposable element Lecture 6 - Recombination of DNA Types and Examples of Recombination: Replicative recombination Lecture 6 - Recombination of DNA Detecting Recombination: ▪ Can be detected by Recombination Detection Program (RDP) is a program that applies a pairwise scanning approach to the detection of recombination amongst a group of aligned DNA sequences Lecture 6 - Recombination of DNA Detecting Recombination: Chen, S. P., Yu, M., Jiang, T., Deng, Y. Q., Qin, C. F., Han, J. F., & Qin, E. D. (2008). Identification of a recombinant dengue virus type 1 with 3 recombination regions in natural populations in Guangdong province, China. Archives of virology, 153, 1175-1179. Lecture 6 - Recombination of DNA Advantages of Genetic Recombination: 1- Genetic recombination provide a constant DNA homogenization within the species and, therefore, the species integrity as an elementary structure responsible for the preservation and rise in the level of ecological stability of organisms in evolving lineages 2- It makes new combinations of alleles along chromosomes, and it restricts the effects of mutations largely to the region around a gene, not the whole chromosome Lecture 6 - Recombination of DNA Advantages of Genetic Recombination: 3- Over time, recombination will separate alleles at one locus from alleles at a linked locus • A chromosome through generations is not fixed, having many different combinations of alleles, this allows nonfunctional (less functional) alleles to be cleared from a population • If recombination did not occur, then one deleterious mutant allele would cause an entire chromosome to be eliminated from the population • However, with recombination, the mutant allele can be separated from the other genes on that chromosome, and then negative selection can remove defective alleles of a gene from a population while affecting the frequency of alleles only of genes in tight linkage to the mutant gene • Conversely, the rare beneficial alleles of genes can be tested in a population without being irreversibly linked to any potentially deleterious mutant alleles of nearby genes Lecture 6 - Recombination of DNA Disadvantages of Genetic Recombination: 1- Recombination can separate the advantageous traits of the organisms 2- Sometimes the important gene combinations that helped the organisms survive and produce maximum progeny get separated into offspring due to new combinations