In biology, recombination is understood to mean the rearrangement (re-) of genetic material ( DNA , RNA ) in cells and, in a narrower sense, the exchange of alleles . Recombination results in new combinations of genes and traits . Recombination and mutation cause genetic variability within a population . Genetic variability, in turn, is the basis for adaptation to changing environmental conditions in the microevolution process .
Recombination through sexual reproduction
In the sexual reproduction of eukaryotes such as plants and animals there is a nuclear phase change , i.e. H. a periodic change between a haploid and a diploid phase in reproduction from one generation to the next. The sexual recombination affects the entire genome in these species, making it the most profound form of recombination. There are two types of recombination:
- Interchromosomal recombination , by recombining whole chromosomes in the chromosome set .
- Intrachromosomal recombination , through new combination of alleles within chromosomes as a result of crossing-over during the 1st meiosis.
Either way, during sexual reproduction, the genetic variation of the following generation is considerably increased, with individual sections of the genome appearing in various combinations with others. In relation to the population of a species, this may result in advantageous combinations as well as potentially detrimental ones. But compared to asexual reproduction, this also enables a higher rate of adaptation, an accelerated adaptation process of the population. This also applies if a mutation occurs, because it does not remain bound in a genetic combination. It therefore disappears faster as unfavorable or spreads faster as beneficial than in the case of asexual reproduction - with a dynamic that is reflected on the molecular level.
Two phases can be distinguished for interchromosomal recombination:
- The distribution of chromosomes in meiosis on ( haploid ) germ cells.
- The fusion of the germ cells to form the ( diploid ) zygote during fertilization.
The number of interchromosomal recombination possibilities depends on the number of chromosomes. For example, for a chromosome set consisting of 2 pairs of homologous chromosomes (e.g. 1 a 1 b , 2 a 2 b ), several different divisions into simple chromosome sets are possible (1 a , 2 a ; 1 a , 2 b ; 1 b , 2 a ; 1 b , 2 b ), here because 2 2 (= 4).
In a block with 23 pairs of chromosomes as in humans are 2 23 (= 8,388,608) possible combinations optionally to form haploid germ cells different interchromosomal. Since two sex cells fuse with each other during fertilization, theoretically 2 23 · 2 23 = 2 46 (≈ 70 trillion ) possibilities for the new combination of chromosomes of euploid chromosome sets result for the offspring of a human couple . Because of this interchromosomal recombination, it is almost impossible to have two genetically identical offspring in human sexual reproduction unless they are identical multiples .
In addition, intrachromosomal recombinations are possible by exchanging segments between paired chromatids. At the beginning of the 1st meiotic division (in the zygotene of the prophase of the reduction division) the homologous chromosomes that have already been duplicated are superimposed in pairs and thus form homologous pairs. The two chromosomes have two sister chromatids each and, when paired, form a unit of four chromatids, a so-called tetrad . Their mutual exact assignment is mediated by a zipper-like connecting synaptonemal complex as a temporary inner protein framework (in the pachytan of this prophase I). At this stage, at points of close contact - with the formation of recombination nodes - there can be mutual accumulation of non-sister chromatids and a crossover can occur. Such areas later appear as a criss-cross superposition, called the chiasma (in the diplotene of prophase I).
Meiosis may extend achiasmatisch, in most cases, however, occurs in almost every nibble on at least one chiasm, often several. During the separation of the paired chromosomes (in anaphase I), the chiasmata are dissolved in such a way that sections of the chromatids are now exchanged for one another. These chromatids no longer carry alleles inherited from one parent alone, but rather parts inherited on both the maternal and paternal sides. This enables them to represent a new combination of gene variants within a chromosome.
The intrachromosomal recombination as a result of a single crossover in a tetrad can lead to four chromatids, each with a different combination of alleles. The previously identical sister chromatids of an X-shaped chromosome are then different. In the further course of the 1st meiotic division they remain connected to the centromere and are thus jointly assigned to one of the two daughter nuclei. The pairs of homologous chromosomes are pulled apart by fibers of the spindle apparatus and the paired non-sister chromatids are separated from one another. The division into cell nuclei is followed by the division of the cell into two daughter cells. The subsequent 2nd meiotic division (equation division) of both cells finally results in four haploid cells, their respective chromosome set consists of one of the four chromatids of each tetrad and is therefore genetically different.
Since the number of crossover events and their locations vary from meiosis to meiosis, the number of intrachromosomal recombination possibilities cannot be precisely stated. If one assumes only one crossover for each of the tetrads, there are already 4 23 (≈ 70 billion) possibilities for a new combination of alleles in the simple (haploid) chromosome set for a chromosome set like the human one . Without the exchange of sections of homologous chromosomes, however, the intrachromosomal combination would remain unchanged. In this case there would be ≈ 8.4 million possibilities through interchromosomal recombination to individually form different egg cells or sperm cells (see above ).
Recombination through parasexual processes
Parasexuality occurs with bacteria and some fungi . There is either a transfer of parts of the genome or cells that have arisen in a non-sexual way (vegetative cells) fuse. A transfer of genome parts can take place through the following processes:
- Conjugation , a direct transfer of genetic material between two interconnected cells.
- Transduction , a transfer with the help of viruses.
- Transformation , through the uptake and integration of extracellular DNA into the genome of a cell.
In eukaryotes, recombination is not limited to meiosis and the germ cells . DNA rearrangement ("DNA rearrangement") can also occur in somatic cells . This affects gene expression. Examples are transposons (“jumping genes”) and the somatic recombination of immunoglobulins, see V (D) J recombination .
Homologous and non-homologous recombination
The homologous recombination (HR) occurs in all organisms. Homologous, double-stranded DNA sections are required. Homologous means that there are great similarities in the nucleotide sequence . In the case of double strand breaks, the damage can be repaired by homologous recombination by using the information on the undamaged chromatid as a template. HR is therefore a tool used by the cell to repair gene mutations . Homologous recombinations usually proceed according to the following scheme:
- Parallel approach (“pairing”) of two double-stranded DNA molecules so that the areas of similar (homologous) nucleotide sequences are at the same level.
- A crossing-over can now occur in a complex process . During this process, DNA segments are exchanged between the two “paired” DNA molecules.
- The location at which the exchanged DNA segments are re-linked can be anywhere within the homologous nucleotide sequences.
- The breaking and reconnection of the DNA molecules is carried out by specific enzymes, the so-called recombinases, so precisely that no nucleotide is lost or added.
The so-called Holliday structure occurs in the course of HR .
The ratio of homologous recombination (HR) to non-homologous recombination can vary by several orders of magnitude in different species. Within the plants , especially with the deciduous moss Physcomitrella patens, there is such a high HR rate that genes can be specifically switched off in order to analyze their function. This technique is called gene targeting "( English gene targeting )", the methodical approach is called " reverse genetics ".
A targeted (i.e. not random) integration of DNA into a genome can also be done by sequential recombination. This non-homologous recombination is brought about by an enzyme , as is e.g. B. encoded by bacteriophage λ , the so-called integrase . The integrase brings together two non-homologous sequences of two DNA molecules, catalyzes their cleavage and connects them together. For example, a virus genome can be incorporated into a chromosome at a designated location.
Recombination in genetic engineering
In the genetic engineering tools are available today, with the help of recombinant DNA synthesized and can be introduced into organisms. In the course of cloning , DNA is usually cut with restriction enzymes at specific recognition sequences and relinked with ligases . Often plasmids or viruses serve as vectors to transfer the recombinant DNA into the target organism.
A novel alternative to conventional DNA cloning with restriction enzymes and ligases are technologies based on homologous recombination, such as recombineering and the RMCE cassette exchange process .
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