Genetics, also called heredity, is the study of genes, their variations, and heredity within an organism. It is divided into three subgroups: Classical genetics, molecular genetics, and epigenetics.
Classical genetics
Classical genetics is the oldest field in genetics. This traces its origins to Gregor Mendel, who described the process of inheritance of monogenic hereditary traits (traits whose expression is determined by only one gene). However, Mendel’s rules only apply to organisms that have inherited two sets of chromosomes from both parents, which is the case with most plants and animals. With the discovery of gene linkage, which states that some genes encoding a particular trait are inherited together, Mendel’s rule that all genes divide independently during meiosis (cell division process that reduces chromosome number by half and occurs during sexual reproduction) was disproved and Mendel’s rules themselves were called into question. Said rule applies only to genes on the same chromosome – the closer the gene distance, the higher the probability of common inheritance. After discoveries such as the genetic code (DNA and mRNA) or cloning (methods of obtaining and identical duplication of DNA), genetics evolved beyond classical genetics.
Molecular Genetics
Molecular genetics, also called molecular biology, is the part of genetics that deals with the structure, function, and biosynthesis of the nucleic acids deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) at the molecular level. Furthermore, molecular genetics is concerned with interacting at the molecular level with each other and with various proteins, as well as the study of gene expression (genetic information of a gene), gene regulation (control of the activity of genes), and protein function within a specific cell. Molecular biology techniques are largely applied to research in medicine and biology. Examples of commonly used techniques include polymerase chain reaction (PCR; in vitro amplification of DNA), DNA cloning, and mutagenesis (the generation of mutations in the genome of a living organism). The subject was given its name in 1952 by the molecular biologist and physicist William Astbury, who played a major role in shaping molecular genetics.
Epigenetics
Epigenetics deals with heritable molecular traits whose basis is not the DNA sequence. The prefix epi- (Greek : επί ) states that modifications “on” the DNA are considered instead. A distinction is made between the subfields of methylations (addition of CH3 groups) and histone modifications (histones = proteins wrapped by DNA, whose unit “octamer” consists of two copies of the proteins H2A, H2B, H3 and H4). The central DNA methylation in humans is that of the nucleic base cytosine in so-called CpG islands of DNA. In said islands, guanine bases are followed by cytosine bases (“CpG dinucleotide”). 75 % of the CpG islands are methylated. The effect of the methylations is mediated by methyl-binding proteins. These cause a closing of the nucleosome conformation (nucleosome = unit of DNA and a histone octamer). Consequently, methylated sites are much more difficult to access by transcription factors (TPFs; proteins that attach to DNA and act on transcription). Depending on the location of the methylations, they have a transcription-inhibiting (transcription = transcription of DNA into RNA) or transcription-enhancing effect. Methylation is catalyzed by a wide variety of DNA methyltransferases – demethylation (removal of the methyl group) by demethylases. Methylation is considered to be the evolutionarily oldest function in the sense of a permanent silencing of a large part of the transposons (DNA elements that can change their locus (location), whereby the removal or new addition of these elements can lead to mutation events of a potentially pathological nature). If these methylations are located at promoter regions, the accumulation of specific TPFs is significantly reduced. Thus, transcription of the DNA segment is not possible. Methylations at enhacer sequences prevent the attachment of transcription-enhancing TPFs. Methylations at non-regulatory sequences reduce the transcription rate due to low binding affinity of the DNA polymerase to the DNA.Only methylations at silencer sequences of DNA can contribute to the increase of transcriptional activity, as they prevent the accumulation of transcription-inhibiting factors. Histone modifications are characterized by the addition of a variety of chemical groups to the side chains of the amino acids of histone proteins. The most common of these are acetylations and methylations. Acetylation affects only the amino acid lysine and results in neutralization of the positively charged lysine. The interactions with the negatively charged DNA decrease, leading to a loosening, i.e. decrease in compaction, of the histone-DNA complex. The result is increased accessibility of transcription factors. Histone methylations also affect the degree of compaction of the nucleosome conformation. Here, however, it depends on amino acids or histone proteins whether opening or compaction occurs. Another special feature is the presence of a histone code. The “succession” of different histone modifications ultimately leads to the recruitment of so-called chromatin modeling factors – depending on the type, these proteins increase or decrease the degree of condensation of the nucleosome confirmation. Therapy (perspective): Since the optimal methylation pattern of cells and cell types is largely unknown, and thus only minor statements can be made about the most ideal protein ratio of the cell, but also the histone code is only fragmentally determined, therapeutic modifications are currently not useful. In the future, however, upregulation and downregulation of genes may be useful in the treatment of diseases such as tumors, mental disorders, and autoimmune diseases, as well as in the anti-aging sector.
