Keywords for Genetics, 2020.

Important: these definitions are for the „A” part of the exam. This is basic knowledge, not enough for passing the exam. Might change a little during the semester as I try to correct existing mistakes.

1. The nature of genetic material. DNA and its structure. Higher organization of DNA. RNA in inheritance.

Genetic material – chemical substances which carry inheritable information. In living organisms this is basically the double stranded DNA. In non-living it can be DNA, RNA also (for example some viruses) or proteins (e.i. prions)

Genome – the whole genetic information of an organism. For example in eukaryotes it can comprise of chromosomal and extrachromosomal genetic material (e.g. mitochondrial and plastid DNA).

Transformation – an event in which a cell (e.g.: prokaryotes, yeasts or even human cells) acquires new features through the uptake of new genetic material  cells transform into something new. Typical example: non-virulent bacteria become virulent by up taking DNA that carries virulence information.

Prions/prion proteins – normally a protein associated with cell membrane, which is when functioning normally is needed for healthy cells. BUT when its structure changes, this leads to abnormal function and causes prion diseases. It can be regarded as genetic information, because this information is passable to other proteins and organisms. The defected proteins contain beta sheets, not alpha helixes.

DNA – deoxyribonucleic acid. DNA is the genetic information carrier chemical substance in living organisms. It is composed of deoxyriboses, phosphates and organic nucleobases. Its basic form is the B form, where there are two strands running in an anti-parallel way. DNA is a macromolecule, a polymer and its subunits are called nucleotides.

Nucleoside – a component of nucleic acids. It only contains a pentose and a nucleobase.

Nucleotide – can be subunit of nucleic acids. A nucleotide is composed of nucleoside and phosphate(s). E.g.: AMP, ADP, dTTP, etc.).

Nucleobases – are nitrogen containing, aromatic parts of the nucleosides/nucleotides/nucleic acids. In nucleic acids they basically determine the specificity. They can be subgrouped to purin (adenine, guanine) and pirimidine (thymine, cytosine and uracil) types.

Phosphodiester bond – is a covalent bond between nucleotides in one strand, for example in DNA. In case of DNA, the participants in forming the bond are the 5’ phosphate of a nucleotide and the 3’ OH group of the adjacent nucleotide.

Complementarity – in DNA (and sometimes in RNA) hydrogen bonds form between nucleotides that are „in front of each other”. These bonds form by specific pairing of nucleobases: adenin with thymine and cytosine with guanine in case of DNA. Can be seen in case of RNAs, also.

DNA denaturation – in case of for example of high temperature the two strands of double stranded DNA becomes separated, because the high temperature diminishes the hydrogen bonds.

Melting temperature (Tm) – the temperature where 50% of the given DNA becomes separated.

GC ratio – it shows how much guanine/cytosine can be found in given DNA (~in genome). This primarily defines the melting temperature, which is a characteristic of a living organism.

DNA hybridization – processes and procedure/techniques in which separated DNA strands try top air up with DNA (or RNA strands). This can be used for example for evolutionary studies or in forensic science. Techniques like microarray and southern/northern blots are based on hybridization.

Superhelicity of the DNA – the phenomenon, when dsDNA twists further more around itself. This can happen in passive way or an active way, the latter with the help of topoisomerases. This feature of DNA structure helps to make the DNA more compact, so it can fit in cells.

Topoisomerases –enzymes that can change the topology of DNA by cutting and reconnecting the DNA strands. They have crucial roles in forming and removing DNA superhelicity, and stopping the torsional tension. Some topoisomerases cut only one strand, others cut both strands of the dsDNA.

Nucleosome – The basic unit of chromatin, that is composed of DNA and central histone proteins. DNA twists around the histone octamer protein complex (H2A, H2B, H3 and H4 – 2 times) about 2x. The loose structure of nucleosomes gives the so called beads-on-string structure. These are found in eukaryotes.

Chromatin – chromosomal DNA of the nucleus + RNA around the DNA and all the protein that attach to DNA is called chromatin. Microscopically (and functionally) there are 2 types: euchromatin and heterochromatin (facultative and constitutive).

Euchromatin – the loose part of chromatin. Active genes are found here, and transcription (RNA synthesis) can happen, mostly with the help of transcription factors. Free DNA and beads-on-string structure form the euchromatin. On microscope, it is the lighter part region of the nucleus. It can transform into facultative heterochromatin.

Heterochromatin – the compact region of chromatin. Here there is no transcription, because genes cannot be activated, or there are no genes here. This denser structure is formed by the further compaction of the „beads-on-the string” into the 30 nm and even more into the 300 nm structure. With microscope it can be visualized as the darker part of the nucleus. Two forms: a. facultative heterochromatin – it can change to euchromatin if needed and b. constitutive heterochromatin – since there ain’t no genes here it, always stays heterochromatic.

Metaphase chromosome – a chromosome that is in the most compact form, it can only be found in cells that are in metaphase of mitosis or meiosis. It consists of two sister-chromatids which are only attached at the centromer region by cohesin proteins. After sister-chromatid separation in anaphase (mitosis) or anaphase II (meiosis II), during the formation of the daughter nuclei these sister- chroamtids will be named chromosomes again.

Centromere – part of the linear chromosome, where kinetochore complex can be found. The region where during metaphase, the sister-chromatids are attached to each other in case of metaphase chromosomes. The kinetochore complex binds microtubules during mitosis and meiosis and is essential for sister-chromatid or chromosome separation. The centromer is usually in constitutive heterochromatin state; also there are no coding regions here.

Telomere – the end region of the linear chromosome. It is constitutive heterochromatin, so it doesn’t contain any genes. It is composed of DNA, histones, but also specific proteins such as Shelterin and Sir proteins. The DNA here contains hundreds of tandem repeats, which in, for example „average” somatic cells after every DNA replication and cell division gets shorter and shorter. In some cells there is an enzyme called telomerase which can recreate telomere (for example in embryonic stem cells, in gamete producing germ cells, and unfortunately in cancer cells).

Replicative senescence – most mammalian cells, including the majority of human cells has this property. These cells have limited number of possible cell divisions to carry out. This is due to that the telomere gets shorter and shorter every time after each DNA replication and thus after mitotic cell divisions. After about 50-60 replication and cell divisions, the cell cannot make more divisions and they will stay in senescence or in some cases they do apoptosis.

Telomerase – a specific enzyme that can restore the length of telomeres. It has protein and RNA part. In healthy humans it only works in stem cells and gamete producing germ cells. In case of cancer, usually it is reactivated in the tumor cells, thus providing immortality for the tumor cells.

Karyotype – the total chromosome content of a cell/organism. We can artificially differ microscopic and electrophoretic karyotypes.

Microscopic karyotype (~karyogram) – usually it means the ordered profile of metaphase chromosomes. Chromosomes are ordered by size in a decreasing manner, and giving them numbers, except for the sex chromosomes, which are shown in the last position in a karyogram.

Ploidity – shows that how many complete sets of homologous chromosomes a cell/organism carries. Usually it is designated with „n”. For examples fission yeast is monoploid: „1n”; or humans are diploid so they are „2n”s.

Euploid – those cells that carry the integer multiple of the complete chromosome set: haploid/monoploid (1n), diploid (2n), triploid (3n), etc.

Aneuploid – those type of cells that also carry non-complete chromosome set(s) in addition to the complete sets. We can subgroup them to hyperploids (carry more) and hypoploids (carry less).

Autoploids – carry 2 or more copies of the same monoploid chromosome set.

Allodiploid=amphihaploid – carry 2 different monoploid sets of chromosomes, that have different origin (2 x 1 n). Usually sterile – cannot produce gametes.

Allotetretrapoid=amphidiploid – carry 2 different diploid sets of chromosomes, that have different origin (2 x 2 n). Usually capable of reproduction.

Hypoploid – it carries 1 or more complete sets of chromosomes and 1 or more incomplete sets. E.g.: nullisomy; monosomy (in human - 45, X=Turner syndrome).

Hyperploid – it carries 1 or more complete sets of chromosomes and 1 or more extra chromosomes. E.g.: trisomy (47, +21 = Down syndrome).

Nondisjunction – chromosome pairs (in meiosis I), and sister-chromatids (in mitosis, and meiosis II) are wrongly or not separated. This leads to unequal chromosome content in daughter cells. These abnormal chromosome contents can lead to death of the cell, or non viable zygotes, also can lead to tumor development, trisomy, monosomy, etc.

Structural aberrations/abnormalities/mutations of chromosomes – Changes in the DNA that affect long sequence regions: inversion, deletion, duplication and translocation. Usually it results in serious defects: still born babies; developmental disorders, cancer formations, etc.!!!!! Not to be mistaken for point mutations and ploidity disorders!!!

Philadelphia chromosome – a chromosomal structural disorder that might happen in leukocyte producing cells. It is the result of reciprocal translocation between chromosomes 9 and 22, which results in different leukemia, such as acute lymphoid leukemia (ALL).

Endomitosis – there is mitosis, but no follow up cell division is carried out. This results in more nuclei in a cell. E.g.: during early Drosophila melanogaster embryonic development.

Endoreplication – replication happens, but mitosis and cell division are not carried out. E.g. Drosophila melanogaster polytene chromosomes in salivary glands.

RNA viruses – viruses that during their development there is no DNA phase. Their „genome” is RNA, which can be single stranded (ss) or double stranded (ds). E.g.: togavirus, which causes rubella.

Retroviruses – virus that have RNA as „genome”, but during development there is DNA phase. These viruses produce DNA in the host cell with their reverse transcriptase and then this viral DNA is integrated into the genome of the host by the viral integrase enzyme. This is called provirus. One example is the HIV, human immunodeficiency virus that causes the AIDS.

Viroids – disease causing agents which are only composed of a circular RNA, they don’t have capsid. Human example: hepatitis D.

Virus-like particles – agents, that cannot actually cause infections and usually their „genome” is RNA (rarely DNA). The only way to spread, as we know, is by the host cell’s cell divisions. If they leave the cell, they cannot infect another cell. E.g.: killer toxin VLP in yeast.

2. DNA replication and repair

Central dogma of molecular biology – cells contain their genetic material in form of DNA, and this DNA is replicated so the daughter cells can get (usually) the same DNA content. On the other hand the genetic information is expressed through the DNA  RNA  peptide/protein flow. The DNA  RNA flow is called transcription and RNA  peptide/protein is called translation. These processes are all part of the central dogma.

Replication of DNA – the whole process that leads to the duplication of the total DNA, leading two exact copies of the DNA. Although the synthesis is carried out by DNA dependent DNA polymerases, it is helped by several other proteins, such as helicase, topoisomerase, etc.

Leading strand – during replication, the strand on which the DNA synthesis happens continuously.

Lagging strand – during replication, the strand on which the DNA synthesis happens discontinuously by Okazaki fragment production.

Okazaki fragment – short DNA parts (around 2000 bp in length) and RNA that are produced on the lagging strand. These fragments will be linked together by ligase enzyme after the degradation of the RNA primer and replacement with DNA by DNA polymerase.

DNA dependent DNA polymerase – enzymes that are capable of synthesizing DNA using DNA templates. Though they need a short sequence to start their activity, because these DNA dependent polymerases need a starting sequence to do the attachment of the next nucleotide. This is called primer in case of DNA replication and is made of RNA. They do the synthesis in a 5’3’ manner.

Sliding clamp – component of the DNA polymerase complexes, which helps the enzyme to stay on the DNA strand and not to fall off. This increases the processivity (better performance) of the DNA synthesis.

Replication fork – the place/structure where the replication is just happening. Here the two „old” strands of the DNA are separated. This is the region where bunch of proteins and enzymes attach and work, such as helicase, DNA polymerase, SSB proteins, etc.

Helicase –this protein helps to detach the two DNA strands from each other in the replication fork. Its mechanism is ATP dependent.

SSB (single strand binding) proteins – are small proteins that are able to attach to single strand DNA and to prevent the DNA to reform the double stranded form. It works for example during DNA replication.

Primase – a DNA dependent RNA polymerase enzyme that is able to produce the so called primer. These primers are indispensable for the start of DNA synthesis.

DnaA – proteins that are able to bind to the specific sequences of the replication origin and can initiate the DNA synthesis. They are the replication initiation proteins.

Replication origin – those specific DNA regions where the replication initiation proteins can attach to. This is where replication of the DNA. In circular prokaryotic DNA usually origin is found, while in the linear chromosomes of the eukaryotes there can be several thousands.

Reverse transcription – that enzymatic process, when from RNA template DNA is being produced. This reaction is catalyzed by the reverse transcriptase. The telomerase enzyme is a reverse transcriptase in specific human cells (e.g. stem cells, germ cells); reverse transcriptase is also a key enzyme for the HIV.

Polymerase chain reaction (PCR) – a group of molecular techniques that is widely used in biology, clinics and forensic science. With this, one can easily amplify given regions of DNA with the use of: template DNA, region specific primers (DNA not RNA in this case); heat stable DNA polymerase; buffer; deoxyribonucleotides (dATP, dCTP, dGTP, dTTP) and a thermal cycling machine. Series of events: 1. denaturation 2. primer annealing 3. polymerization, then repeat the steps. Theoretically after every cycle there is two times the DNA is present as before the previous cycle.

DNA repair – all the processes that help the cell to fix the faults of the DNA. Example: excision repairs, SOS repair, etc.

Proofreading repair – a type of DNA repair which happens during replication. When the DNA polymerase builds in the nucleotides according to the base pairing rules, it always checks if the built-in is correct. If not, then it removes the nucleotide and then builds in the correct nucleotide. This is a very efficient way to help correctly replicate the DNA, because only 1 mistake happens to 109 base length DNA syntheses in average.

Photoliase – an enzyme that repairs the UV induced T-T dimer formation. It is the main enzyme for the photoreactivation repair mechanism, which curiously is missing from human.

O-methyl-transferases – enzymes that helps to correct unwanted methylations (and other alkylations) of nucleotides in the DNA. These enzymes are single-use enzymes, since after receiving the alkyl group from the DNA, they are destroyed („suicide enzyme”). One example is the O6-metil-guanin transferase.

Excision repairs – a group of DNA repairs that when mistakes are detected they cut out short-longer regions from the DNA strand and then resynthesises that missing part. It is essential that this system is able to recognize the original strand in the dsDNA. Two main types: base excision repair and nucleotide excision repair.

NER – nucleotide excision repair – excinucleases cut out the region that contains the mistakes (for example T-T dimer) and the missing part will be resynthesized. Two major types: I. GG-NER – always active „global” surveying and repairing system. II. TC-NER – „not global” – it is activated if a mistake is recognized in a transcriptionally active region.

BER – base excision repair – constantly works in the cell. When a fault in the DNA is recognized, either a nucleotide is cut out (short patch) or several nucleotides are cut out (long patch). It is called base excision repair because first the faulty base is removed by glycosidase. Then comes the nucleotide removal and a DNA polymerase comes to fills in the gap and finally ligase connects the loose ends.

Mismatch repair – a protein system which can recognize and correct those mistakes that are created by insertion, deletion of nucleotides during DNA replication and recombination. Major components: MutS, MutH, MutL, DNA polymerase, ligase.

Recombinational DNA repair – those repair mechanisms that involve the recombinational apparatus to fix the faults of the DNA. This is one, but not the only way to fix double stranded DNA breaks. It is also possible to repair specific type of T-T dimer mutations.

SOS repair – a repair mechanism that if there is too much faults in the DNA and general repairs, it still allows the replication to continue. Some of the proteins that are involved in this repair mechanism: RecA, LexA. This system can be found for example in E. coli. It is a mistake generating repair mechanism.

End joining repair – very important repair mechanism that can fix double stranded DNA breaks. It allows free ends of DNA to be linked, although some nucleotides are removed during this mechanism. It generates mutations.

3. Cell cycle, mitosis and cell division.

Cell cycle – is a feature of eukaryotic cells. It includes G1, S, G2 and M phases in this strict order, which results in two genetically equal cells. Some cells leave the cell cycle, including human terminally differentiated cells. This stage when the cell is not in the cell cycle is called G0 phase.

Mitosis – this event is part of the M phase of the cell cycle. During this process the already replicated genomic DNA is distributed into two nuclei. We can also say that it is the division of the nucleus. Major stages of mitosis: prophase, (prometaphase), metaphase, anaphase and telophase.

Centrosome – a cell organelle, which contains two centrioles and its major function is the generation of microtubules. During mitosis, meiosis I and meiosis II it helps to generate the mitotic spindle, which helps to correctly separate the sister-chromatids and chromosomes.

Kinetochore – a protein complex found in the centromere region of the chromosome. During mitosis and meiosis I and II, the so called kinetochore microtubules attach here and allow the chromosomes to be correctly positioned and separated to the daughter nuclei.

Sister-chromatid – in S phase DNA is replicated, and these two copies of the DNA stay together until they are separated in mitosis or meiosis II. These attached DNA double helixes are called sister- chromatids. At metaphase they are held together only at the centromere region (with the help of cohesin protein). During mitosis and meiosis II sister-chromatids are separated and transferred to the daughter nuclei and become the chromosomes.

Cohesin – proteins that hold the sister-chromatids together, after the replication of the DNA. In metaphase they are only found in the centromere region, but still holding the sister-chromatids together. At the metaphase/anaphase transition even these cohesins are degraded (in mitosis and meiosis II) by the separase enzyme, so the anaphase can start, and sister-chromatid separation and migration happens.

Separase – is an enzyme responsible for the degradation of cohesins. It is activated at the end of metaphase resulting in the separation of sister-chromatids and lets the mitosis or meiosis II to pass to its anaphase.

Cytokinesis – it is part of the M phase of the cell cycle/mitotic cell division, but also there is cytokinesis after meiosis I and meiosis II. It means the actual cell separation of the cell, after the daughter nuclei have formed. From one cell two daughter cells are formed. In the process of this event, the so-called contractile ring has the key role, which is composed of myosin motor protein and actin microfilament.

Contractile ring (= actomyosin ring) – it makes the eukaryotic cell separation possible. It is a biomechanical structure, which starts to form during the telophase. It is mainly composed of actin microfilaments and myosin motor protein. The contraction of the ring pulls in the cell membrane, and the complete invagination marks the end of the cytokinesis and results in the separation of the cell into two daughter cells.

Mitotic mosaics – during the development from zygote to the new multicellular organism, cells carry out series of mitotic cell divisions (from 1 cell to multicellular organism, such as humans). During some of the mitosises, malfunction might happen resulting in nondisjunction, which means the sister- chromatids are not properly separated and can result in uneven distribution of the chromosomes in the daughter cells (carrying more or less chromosomes than supposed). Since it doesn’t affect all the cells, not the whole body will be affected. In some cases partial Down syndrome can develop, but several other diseases/syndromes are associated with this phenomenon.

4. Gene expression and its regulation. Some basic epigenetic phenomena.

Gene expression – generally it means how the genetic information (which is stored in the DNA in living organisms) is manifested. Gene expression includes the events of transcription, translation and the regulatory process of these events. If a protein coding gene is expressed, then we can find its product also, that is the protein.

Transcription – when DNA sequences are written into RNA sequences = the genetic information found in the DNA is transferred into RNA form (any kind of RNA, including mRNA, tRNA, rRNA, miRNA, etc).

DNA dependent RNA polymerases – enzymes and enzyme complexes that are responsible for RNA synthesis, using a DNA template. During polymerization, ribonucleotides are built into the RNA in 5’  3’ direction.

Gene – a DNA sequence that includes promoter, protein or RNA coding sequence(s) and termination sequence. These regions make up the transcriptional unit, that we call gene. Genes are also known as „cistrons”.

Promoter – part of a gene. DNA sequence that marks the location of a „gene” thus determining the DNA sequence that is determined for transcription and also determines where exactly should the transcription start. This is the place where RNA polymerase binds to the DNA in prokaryotes with its sigma factor. In eukaryotes here can build up the transcriptional pre-initiation complex in case for example the TATA box type promoter.

Bacterial RNA polymerase – is a multiple subunit protein complex. The holoenzyme form, which also includes the sigma factor, is responsible for recognizing the promoter and starts transcription. For elongation the sigma factor is not needed, only for promoter recognition. There are several types of bacterial promoters, and according to these different types of sigma factors.

Rho factor – a protein in prokaryotes, which is responsible for transcription termination, when it happens in a Rho factor dependent way. During this type of termination process the Rho factor recognizes the so-called Rut region of the RNA and with use of ATP it stops the synthesis of the RNA.

Operon – the prokaryotic transcriptional unit and its regulation. It is usually composed of regulatory sequences: promoter, operator and structure genes (and terminator). E.g.: lac operon.

Polycistronic mRNA – mRNA that is transcribed from one gene, but it codes more polypeptide chains. E.g. in case of some of the prokaryotic operons, such as lac operon, as it its mRNA will be translated into 3 different polypeptides. On the other eukaryotic mRNAs are monocistronic, because 1 mRNA stands for 1 polypeptide chain.

DNA element – those DNA sequences that can bind proteins. Usually they are involved in the regulation of gene expression. Examples of DNA elements: promoter, TATA box, enhancer, etc.

TATA box – a type of DNA element that binds the TATA binding protein (TBP) and is partly responsible for the initiation of TATA dependent transcription. It has role in the recruitment of other general transcription factors, and the RNA polymerase II, so the transcription can start. It is a eukaryotic type of promoter sequence, but not all eukaryotic genes are regulated by TATA box.

General transcription factors – proteins that gather in the promoter region (and bind to it) and are indispensible, for example for the TATA box dependent transcription in eukaryotes. E.g.: TFIID, TFIIH, etc.

Enhancer – a type of DNA element that can bind specific transcription factors (or aka activator proteins). Usually it is found „far away” from the gene it regulates, but on the same DNA strand, and usually upstream of the gene. If it is activated, then it activates the regulated gene(s) with the help of the Mediator complex and starts the recruitment of general transcription factors and RNA polymerase II to initiate for example the transcription of TATA dependent genes.

Pre-initiation complex (PIC) – a huge multiprotein complex that is responsible for the start of transcription, for example in case of TATA dependent genes. Some of its protein components are: activator protein(s), Mediator complex, general transcription factors, RNA polymerase II, etc.

Specific transcription factor (= activator protein) – a type of protein, that is for a given reason appears and can bind to the enhancers of given specific genes and is responsible for the initiation of transcription of these specific target genes. It is one of the possibilities of gene expression regulation on a DNA level. E.g.: MyoD, which turns on the expression of those genes that are needed to for somite cells to become myoblast cells.

DNA CpG island methylation – in case of CpG island type promoters, the cytosines of these sequences can be methylated by methylating enzymes, inducing heterochromatinization of these regions. This prevents this region from transcription: it becomes inactive for gene expression. It is reversible, because these methylated cytosines can be demethylated, that is it can be euchromatin again. It is important in the regulation of gene expression at the DNA level. It has role in epigenetics.

Histone code – the core histones of nucleosomes (H2A, H2B, H3, and H4) possess so called „histone tails” that are of course composed of amino acids. Some of these amino acids can be posttranslationally modified (e.g. methylation, acetylation, phosphorylation, etc). These modification can happen differently and result in a “code”, that either means that the given chromatin region is in euchromatin state or heterochromatin state. Thus, it has contribution to gene expression regulation on the DNA level. This regulation is an epigenetic regulation.

Positional effect – an epigenetic phenomenon. It does matter where a gene can be found on the chromosome. For example, if a gene is found near a constitutive heterochromatic region (e.g. telomere, centromere, etc.) then sometimes it can become a heterochromatin region, because constitutive heterochromatin „likes” to spread. Such a phenomenon is the positional effect variegation (PEV), which can be seen sometimes in the eyes of fruit flies and also in cases of the formation of colonies by yeast.

Barr body – because of dose compensation, in women one of the X chromosomes becomes inactivated almost completely. The process of inactivation happens by the expression of Xist RNA, which induces the heterochromatinization of the given X chromosomes, and becomes a very condensed dot like structure. Of course the Barr body is found inside the nucleus, usually nearby the inner membrane of the nuclear envelope. Barr body formation is an epigenetic event. rRNA – ribosomal RNA. Those specific RNAs that are components of the ribosomes. In case of prokaryotes, they are coded by 1 „kind” of gene (in several copies), but on the other hand in eukaryotes they are coded by 2 „kinds” of genes (in several copies). They are generated by transcription and after they are modified by posttranscriptional processes to form the mature rRNAs. These mature rRNAs bind to each other and ribosomal proteins to form the subunits of ribosomes. In case of eukaryotes these events take place in the nucleolus, but the whole ribosome is only formed in the cytoplasm, when translation starts.

Ribozymes – RNAs that have enzymatic function. An example is RNase P, which has role in the maturation of tRNAs.

Capping of eukaryotic mRNA – a type of posttranscriptional modification of mRNA, it is part of the mRNA maturation process. It already happens, when just a short part of the mRNA is synthesized. The „cap” is formed on the 5’ end of the mRNA; and it is chemically a methylguanosine, which attaches to the mRNA through 3 phosphates. Usually also a protein binds to this „cap”. The cap helps the transportation of the mRNA from the nucleus to cytoplasm and it also has role in the protection from the degradation by nucleases.

Polyadenylation – a type of posttranscriptional modification that happens to the eukaryotic mRNA. It is a maturation step that starts when the transcription is finished. It happens on the 3’ end of the mRNA by cutting down some of that region and adding several (even hundreds) of adenosines. This process is helped by several proteins and enzymes, but the polyadenylation itself is carried out by the so-called polyadnilate polymerase. Most important functions are protection from nucleases and determining the life time of the mRNA.

Intron – sequence that is transcribed into the pre-mRNA, but during the splicing mechanism it is cut out and will not be part of the mature mRNA. In the end it will not contribute to the protein sequence during translation.

Exon – sequence that is part of the mature mRNA, and it will contribute to sequence of polypeptide. During splicing exons are not cut out, but they are joined together. Mature mRNA only contains the sequences of the exons.

Splicing – a posttranscriptional modification. The process when from pre-mRNA introns are cut out and the exons are joined. There are two major types: a. self-cutting b. spliceosome dependent splicing. It is most common among eukaryotic genes, but not only. (tRNAs are also being spliced)

Spliceosome – is a big complex that contains both proteins and RNAs. Spliceosomes are responsible for the spliceosome dependent splicing. They cut out introns from the immature mRNA and join the exons, so the mature mRNA can be formed. ATP is needed for the spliceosome assembly, but not for the cutting and joining processes.

Alternative splicing – splicing process that results in that, that the mature mRNA will not contain all the exons, this means that some of the exons will be cut out during together with the introns. This means that from 1 gene several different proteins can be expressed. Important: the order of exons does not change! E.g.: sex determination of fruit flies is regulated by alternative splicing; most human mRNAs are also alternatively spliced.

RNA „editing” –processes that change the sequence of RNAs compared to the original genetic information. E.g. apoB100 and apoB48 mature mRNAs – in the latter there is nucleotide change, which results in a stop codon, which results in a smaller peptide than usual. It is not common among mRNAs, but general in case of tRNAs.

Translation – the „transformation” of mRNA sequence/information into amino acid sequence information (polypeptides). It is catalyzed by the ribosome, which is composed of proteins and rRNAs. Reading of mRNAs happens in a 5’3’ way. mRNAs contain code in nucleotide triplets, which is called codon and these codons pair with the anticodons of tRNAs. 1 tRNA can carry only 1 type of amino acid, which means according to 1 codon only 1 amino acid can be built into the polypeptide chain. There are 64 types of codons, but they only mean 20 amino acids (61 codes) and stop (3 codes). ATP, GTP, tRNAs, amino acids, mRNA, ribosome and „helping” factors are needed.

Codon – nucleotide triplets that are found in the mRNA, which code for amino acids. It pairs with the anticodon of tRNA in the ribosome during translation.

Anticodon – the nucleotide triplet of the tRNA that pairs up with the codon of the mRNA during translation.

Point mutation – one or very few nucleotide changes in the DNA sequence. Major types are: substitution, deletion and insertion. Sometimes these mutations are unnoticeable, but can result in serious diseases and abnormalities that even can be lethal. E.g.: cystic fibrosis causing mutations. (not to be mistaken with structural chromosome mutations!!)

SNP – Single nucleotide polymorphism. Alleles, those only differ in one nucleotide. E.g.: in case of the sickle cell anaemia causing HbS allele only differ in 1 nucleotide from the normal HbA allele.

Silent mutation – a mutation resulting in no change of the amino acid sequence. Usually does not cause any phenotype changes. It is the result of substitution type point mutation.

Missense mutation – is a kind of mutation that results in the change of peptide sequence, because the nucleotide change causes amino acid change. It can be without consequences but also can cause serious problems, such as in case of sickle cell anaemia. Result of substitution type of point mutation.

Nonsense mutation – is a kind of mutation that results in a shorter than normal peptide sequence, because the nucleotide change causes an amino acid to change into a stop codon. Usually the protein loses its function and will result in defects or diseases. Result of substitution type of point mutation.

Frameshift mutation – is a kind of mutation that results in a completely changed and shorter polypeptide sequence, because the nucleotide insertion or deletion causes a shift in the reading of the open reading frame (ORF) and ultimately leads to the generation of a stop codon.

Mutagen – an agent that can cause mutations and changes in the sequence of DNA. E.g.: UV radiation, X-ray, ethidium bromide.

5. Meiosis and lifecycles. Laws of Mendel. Mendelian and nonmendelian inheritances. Autosomal inheritance.

Meiotic cell division(s) – a series of events that include all the processes that lead to the formation of haploid cells from diploid cells. Usually, the meiosis of 1 diploid cell results in 4 haploid cells after the two cell divisions.

Gametes - usually we call gametes those cells that take part in the sexual reproduction by fusion and forming the zygote. Gametes are results of meiosis, so they are haploid cells.

Zygote – a haploid gamete (cell) fuses with another haploid gamete (cell) and form a new diploid cell that is called zygote.

Prophase I – the very first step of meiosis I. It is very special phase. This stage of the meiosis consists of five “sub-stages”: leptotene, zigotene, pachytene, diplotene and diakinesis. During this stage is when meiotic crossing over and recombination happen, and these events contribute to the high variability among the gametes.

Synaptonemal complex – is a structure that is formed during prophase I and has function in holding together the homologue chromosomes. It consists of 2 side elements and a central ladder like elements which are made of proteins and which bind the chromatin. Its exact function is not yet completely understood: might not even be necessary for crossing over and recombination.

Bi-orientated kinetochores – kinetochores of a chromosome (with two sisterchromatids) that look to the opposite away direction. It can be seen during mitosis and meiosis II. They make the sister- chromatid separation possible and distribution to the daughter cells.

Co-orientated chromosomes – kinetochores of chromosome (with two sisterchromatids) that look in the same direction. It can be seen during meiosis I, and makes the homologue chromosomes’ separation and distribution possible.

Spermatogenesis in humans – with the meiotic division of germ cell, after a 64 day maturation process haploid gametes (sperm cells) are produced in men. The result of the meiosis of one particular germ cell is four equal sperm cells. The sperm cell can fertilize the oocyte creating the zygote.

Oogenesis in humans – with the meiotic division of the female germ cells oocytes (“egg”) are produced. It takes several years of maturation and it is disrupted several times. The meiosis (thus the oogenesis) completes only right after the fertilization by the sperm cell. The result of the meiosis of 1 particular germ cell is 1 oocyte and 2 or 3 polar bodies, so the oogenesis produces unequal haploid cells.

Neocombination – during meiosis, the random pass on of chromosomes with either paternal or maternal origin (from the germ cells to the haploid gametes), so new combination of chromosome sets are being generated. Along with recombination this increases the variability among gametes.

Sexual cycle – is the alternation of diploid and haploid generations (or phases). E.g.: in humans – diploid organism  haploid gametes  diploid organism  haploid gametes and so on…

Mendelian genetics – those studies all together that investigate how features and characteristics are passed from parents to progeny. It actually describes the principles of neocombination. It must be mentioned that the laws of Mendel are only suitable for genes that are autosomal and their alleles are in dominant-recessive relation and that the genes of interest are not linked or are not in interaction with each other if we study more than 1 gene.

The Law of segregation – during the formation of the gamete the originally paired inheritable determinants separate (= segregate) so that 1 gamete only gets 1 of the determinants found previously in the “pair”. The distribution is random: to chance to get 1 determinant of the pair is 50%, but to receive the other determinant is also 50%. (Now we know that 1 pair of determinants means gene and 1 determinant mean 1 given allele for that particular gene) The Law of uniformity – says that if we cross two homozygous (for 1 or even more genes) parents then the next generation will be all the same for these gene(s) in genotype, thus as consequence in phenotype.

The Law of independent assortment – states that alleles for separate traits are passed independently, from parents to offspring. This is only true when the genes of interest are not linked.

Autosome – non sex chromosomes. A chromosomes that are present in every cell independently of sex. In a human diploid cell there are 22 pairs of autosomes (44 all together) and a pair of sex chromosomes (2 all together: XX or XY). In the haploid cells (gametes) of a human there are 22+1 chromosomes.

Sex chromosomes – those chromosomes that are present depending on the sex, they play part in sex determination (but not only in sex determination). Their distribution depends on sex – human males have an X and a Y; while the females of humans have XX combination of sex chromosomes.

Breed true (and true breeding) – will breed true-to-type when mated like-to-like; that is, that the progeny of any two individuals in the same breed will show consistent, replicable and predictable characteristics. This means they are homozygous for the given genes.

Hybrid – originates from two different genotype parents. Actually a hybrid is heterozygous for given gene(s).

Allele – different versions of a given gene are called alleles (E.g. A and a). Usually the most frequent allele for a given gene is called wild type allele.

Genotype – the allele combination of gene(s) – or we can say genetic composition of an organism. E.g.: aa, Aa; AABBCc.

Homozygote – those organisms that have 2 of the same kind alleles for a gene (or for more genes) – Eg.: AA or aa.

Heterozygote –an organism that has 2 different alleles for a gene (or more genes of course) - (E.g.: Aa).

Phenotype – usually the observable characteristics of an organism, which result from genotype – eg.: tall and small pea plant.

Dominant allele – an allele that is enough to be present in 1 copy to express the characteristic. For example AA and Aa genotype will result the same phenotype, since “A” is stronger than “a”.

Recessive allele – an allele type that has to be present in 2 copies in order to express its related phenotype – e.i. “aa” for example.

Punnett square/table – a cross multiplying square table which shows or predicts the possible progeny genetic combinations.

Test cross – is a cross which can show whether the organism with dominant phenotype is a heterozygote or homozygote. e.g.: AA or Aa crossed with aa (homozygote) and “AA/Aa” are the tested, while “aa” is the testing genotype. Expressivity – how much a genotype is shown in phenotype in a given organism/individual. We can see in human the extra finger phenotype as an example.

Penetrance – in population it shows the proportion of individuals that present the phenotype that is the result of a genotype.

Recessive inheritance – a given type of trait is determined by recessive allele, which of course has to be present in two copies. A good example is albinism in humans.

Dominant inheritance – the given trait is determined by 1 allele (the dominant one of course). E.g. extra finger phenotype.

Intermediate inheritance (incomplete dominance) – it is an inheritance type when the heterozygote will have a “medium” or transitional phenotype form, something like in between the two homozygous phenotypes. 3 possible phenotypes can happen in such an inheritance. E.g.: sickle cell anaemia.

Co-dominance – a heterozygote will show the phenotype for both alleles in the same extent. A good example is human ABO blood group inheritance – if both IA and IB alleles are present then that individual will be AB blood group type.

Gene interaction – a phenomenon when 2 or more genes determine 1 characteristic. Typical example is the epistasis inheritance in case of the color of rodents. Not to be mistaken with genetic linkage.

Inheritance of lethal alleles – in case of essential genes some of the allele types can cause the death of the cell or organism. In human there are lots of examples, such as the dominantly inherited Huntington disease or the recessively inherited cystic fibrosis.

Pleiotropy – means that 1 gene can be responsible for more than one characteristic (phenotype, cell function, etc.). A good example in human is sickle cell anaemia in which there is abnormal hemoglobin, thus abnormal red blood cells are being produced, but also people with the disease have extreme pain, anaemia and other symptoms.

Inbreeding – reproduction among closely related individuals. If it happens repeatedly in a population then it can result in the decline of genetic variance. It results in the increase of recessive homozygosity which is bad for populations and causes decreased health, fitness and reproduction.

Heterosis (heterozygous benefit) – it is when two true breeds are crossed and the resulting offspring will benefit from the heterozygousy. Can be used in agriculture: e.g.: maize.

Multifactorial inheritance – those types of inheritances that are not only determined by genetic background, but also the environment will contribute to the phenotype. Good examples in human: the inheritance of height, weight, etc.

6. Sex determination and sex-linked inheritance

Parasexuality – the neocombination and recombination of parental chromosomes happen without meiosis and gamete production.

True sexuality – production of offspring that involves meiosis and fertilization

Mating type – it is seen in case of phenotypic sex determination, such as in case of yeasts. The sexuality is determined by molecular mechanism and only two different mating type cells can form a zygote.

Hermaphrodite animals – possess both male and female reproductive organs (e.g.: snails, earthworm). XX/XY based sex determination systems – females have two of the same kind of sex chromosomes (XX), while males have two different types (XY). E.g.: mammals, including human beings.

SRY – is a gene that is found in for example male human individuals. It stands for “sex-determining region Y”, which means it is found on the Y chromosome. It defines for the embryo to develop into male by inducing male differentiation and by repressing female differentiation.

Pseudo-hermaphrodites – Despite the given sex chromosomes, the characteristics of the other sex type appear in the phenotype.

ZW sex determination system – females have two different types of sex chromosomes (ZW) and males possess two of the same kind: ZZ. Birds and butterflies usually are like this.

XX/X0 sex determination – a females have 2 of the same type of sex chromosomes (XX), while males have 1 X chromosome (X0). Good examples are grasshoppers.

Haplodiploid based sex determination – sex is determined by the set of chromosomes – telitoky and arrhenotoky are the known forms.

Arrhenotoky – Unfertilized eggs develop into haploid individuals, which are the males. Diploid individuals are generally female, but may be sterile females. E.g.: some wasps, bees, ants, etc.

Thelytoky – diploids are males and haploids are females. E.g.: shield scale.

Sex linked inheritance – inheritance of traits determined by genes located on either X or Y (Z or W) chromosome.

Szexmozaikok – the presence of two populations of cells with different sex chromosomal sets in one individual, who/which has developed from a single fertilized egg (e.g.: fruit fly bilateral gynandromorphy).

7. Recombination events

Genetic recombination – is the process by which a strand of genetic material (usually DNA; but can also be RNA) is broken and then joined to a different DNA (or rarely RNA) molecule.

Meiotic recombination – a DNA exchange that happens during the meiotic prophase I and the exchange happens between the nonsisterchromatids of homologous chromosomes.

Genetic linkage – Genetic loci on the same chromosome are physically connected and tend to segregate together during meiosis, and are thus genetically linked. (don’t confuse with gene interaction)

Linkage group - When genes occur on the same chromosome, they are usually inherited as a single unit. Genes inherited in this way are said to be linked, and are referred to as linkage groups.

Genetic mapping based on linkage – from the recombinational frequencies between genes one can determine the order of the genes, thus can create a genetic map. The basic unit in a genetic map is: 1 map unit (m.u.) or 1 centiMorgan (1 cM) that equal with 1% recombination.

Interference – the phenomenon when a crossing over event has effect on the formation of another crossing over in a nearby region. Mitotic/somatic recombination – genetic recombination can happen during the mitotic cell cycle, but crossing over still happens by the pairing of homologous chromosomes. It happens in somatic cells (diploid), so it is also called somatic recombination.

Sister-chromatid exchange (SCE)) – it is a specific “mitotic” recombination event that involves the sister-chromatids of a “two-sisterchromatid-chromosomes”, there is crossing over in between them and chromosome pieces are exchanged. Usually happens during G2 phase, but also can happen in late S phase.

Harlequin chromosome– a specifically labeled (with BrdU, Giemsa and fluorescence) chromosome that is suitable for the detection of SCEs.