> [!info]- Note Disclaimer > > This note contains > # Chromosomes **Chromosomes** are compact structures that composed of [[Nucleic Acids|DNA]] A cell's **ploidy level** refers to the number of chromosome sets: - **Diploid:** Two copies of every gene *(2n)* - **Haploid:** One copy of every gene *(1n)* Each chromosome contains one allele, because humans are diploid, they have two of every chromosome and two alleles as a result In humans, *somatic (body)* cells are *diploid* and undergo mitosis while *gametes (sex)* cells are *haploid*. --- **Aneuploidy** is when there are is an abnormal chromosome number **Nondisjunction:** failure of homologous chromosomes or sister chromatids to separate properly during meiosis. **Linkage** describes ___ . Synteny (synonymous with homology) ## Types of Chromosomes > See also: > - [[Genes#Relationships Between Genes|Relationship Between Genes]] ![[Homologs and Sister Chromatids.png|350]] **Homologs** (when comparing genomes of separate organisms) are two or more sequences that descend from a *common ancestral sequence*. They are the results of divergent evolution. *Sister chromatids* are genetically identical, whereas a *homologous pair chromosomes* are composed of two different chromosomes that are not genetically identical despite containing the same sets of genes - We wouldn’t refer to a pair of sister chromatids as being homologous ### Chromosomal Mutations - Cytogenic Abnormalities: An irregularity in the number or structure of chromosomes - [ ] Trisomy ## Chromosome Organization > See also: > - [[Deoxyribonucleic Acid (DNA)]] Homologous Chromosomes (two chromatids) 2. Sister Chromatids 3. Chromosomes 4. Chromatin (DNA + Histones) 5. DNA (Double Helix) ![[Pasted image 20240329193200.png|300]] - **Centromeres:** a - **Kinetochore:** a ### Chromosome Variations allele = “other form” - implies a D/d style of genetic pair alkpatonuria - first described human hereditary disease (19) ### Telomeres Telomeres are “safety caps” at the ends of chromosomal DNA that serve to protect it from the cellular environment [[Stem Cells]] use telomerase, a protein that restores telomeres, to protect their DNA and extend their cell division limit The Hayflick limit is the number of times a normal somatic, differentiated human cell population will divide before [[cell division]] stops (due to complications) - ~52 times > In humans, the repeated sequence is **TTAGGG** ## Chromosome Structure ### Nucleosomes **Nucleosomes** are the building blocks of chromatin. - Composed of an octet of histone proteins wrapped around twice by strands of DNA Nucleosomes are removed in preparation for: - DNA Replication/Repair - Transcription - Recombination Because they are so crucial for the protection of DNA, they often are reassembled shortly after. #### Histone Proteins **Histones** are the building blocks of nucleosomes. ![[Histone Protein Structure.png|300]] There are four core types of histone proteins (H2A, H2B, H3, and H4). - There are two copies of each which form an octomeric core. - There is an additional H1 histone protein, serving as the linker between other nucleosomes The core histone proteins are composed of: - a histone-fold domain (structural) - an N-terminal tail (modification target) - Flexible and lacks secondary structure - Imitates the grooves of a screw, causing DNA to wrap around in a left-handed manner ![[Pasted image 20240330000434.png|300]] #### DNA Binding Interactions > See also: > - [[Protein Interactions]] Histones are *not sequence specific* and instead interact with DNA’s negatively charged backbone to make H-bonds with the bases in the *minor groove*. 1. The *H3-H4 tetramer* assembles first. 2. The DNA strand then wraps around the intermediate structure. 3. The *H2A-H2B dimers* then attach, “sealing” the DNA within the nucleosome. When the histone tails contain a large amount of lysines and arginines, the overall positive charge they contain tightly binds to the negatively charged phosphate backbone of the DNA. Because of how overwound DNA becomes (-1.2 linking number per nucleosome), a large amount of energy is stored within these since negative supercoiling favors unwinding. - Toposiomerase will relax DNA that is too overwound ### Chromatin > See also: > - [[Cell Nucleus]] **Euchromatin** (10 nm fiber) - Poor staining - open - unorganized - high transcription > “Beads on a string” > “Eu” → “Useful” --- **Heterochromatin** (30 nm fiber) - Good staining - condensed - very organized - low transcription The nucleus is separated into multiple regions, where the different types of chromatin are grouped together - There is also evidence that the individual chromosomes themselves are also compartmentalized within the nucleus ## Regulation of Chromatin Structure > See also: > - [[Gene Expression]] > [!question] > “If DNA’s usual state is being tightly wound around nucleosomes, how genes be accessed for transcription?” One theory is that alternating AT and GC regions contribute to the binding positions of DNA with histone proteins ##### Chromatin Remodeling Complexes Chromatin remodeling complexes can activate or repress transcription by increasing or decreasing how tightly wrapped DNA is around its histone proteins ##### Chemical Changes to Histone Proteins Bromodomains recognize acetylated lysine Chromodomains recognize methylated lysine --- **Histone Acetyl Transferases (HATs):** Add acetyl groups - Decrease positive charge on histone tail - Decondenses chromatin - Activates transcription **Histone Deacetylases (HDACs):** Remove acetyl groups - Increases positive charge on histone tail - Restores condensed structure - Represses transcription ![[Histone Protein Acetylation.png|150]] --- Methylation of histone tails leads to: - silencing, repression, occasional activation - can be mono, di, or trimethylated Histone Methyl Transferases (HMTs) Histone Demethylases (HDMs) ## Gene Linkage & Crossing Over **Gene Linkage** - Thomas Hunt Morgan used the model organism Drosophila melanogaster (“lets put a bowl of fruit out and see what grows on it”) - Didn’t initially believe in Mendel’s results or the chromosomal theory, instead thought species were created by instantaneous mutations (mutationism) - Tested for mutations by breeding fruit flies over and over again, looking for alternative forms (a new mutation) that could be the basis for new alleles - almost gave up until white-eyed male appeared, assisted in showing that some traits are sex-linked - Some recessive phenotypes can “skip” generations, especially with sex-linked traits - Genes that do not sort independently because they are located on the same chromosome, are said to be linked - ![[Pasted image 20240201055841.png|100]] - The probability that two genes on the same chromosomes will remain together during meiosis ranges from just less than 100% to nearly 50% - Even if the distance between two genes is >50 cM apart, they would only have a 50% rate of linkage **Linkage and Crossing Over** - In 1909, *Frans Janssens* discovered crossing over in salamanders and called it a *chiasmata* - wrote that “chromosome filaments are involved in contacts that can modify their organizaton from one segment to the next. This will generrate new segmental combinations, which will be different for the two filaments of a same chromasome, or which can affect the whole chromosomal segment.” - ![[Pasted image 20240201060904.png|300]] - New combinations of alleles which occur from crossing over are known as *recombinants* - It took a few decades to find proof of crossing over - In 1931, Barbara McClintock and Harriet Creighton studied crossing over in corn - homologous chromosomes are typically identical in shape, however non-identical ones were used in this experiment: one was marked by compacted regions that formed a knob-like structure and extra chromosomal material - the recessive phenotype was verifiable under the microscope - C=colored, c=colorless & Wx=nonwaxy, wx=waxy - the recessive phenotype could only occur as a result of a cross over event ![[Pasted image 20240201061748.png|300]] - chromosomal breakage/rejoining was not technically confirmed until the 1960s with isotopes and phage labeling experiments, but this was a large step towards it