Chromosomes. M.Sc. Biotechnology. Hawler Medical University, Iraq

Transcription

1 Chromosomes Bashdar Mahmud Hussen M.Sc. Biotechnology Hawler Medical University, Iraq

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3 History of Chromosome Karl Nagali (1842) E. Russow (1872) first description A. Schneider (1873) chromosomes & cell division Strasburger (1875) Walter Flemming (1877) chromatin W. Roux ( 1883) chromosome & inheritance

4 Male vs Female MALE Usually the Y chromosome. Y is usually smaller Male genotype = XY FEMALE Usually the X chromosome. Larger than the Y Female genotype XX Except Birds Male = XX Female = XY

5 Number of chromosomes Normally, all the individuals of a species have the same number of chromosomes. Presence of a whole sets of chromosomes is called euploidy. It includes haploids, diploids, triploids, tetraploids Polyploidy. Gametes normally contain only one set of chromosome this number is called Haploid Somatic cells usually contain two sets of chromosome 2n : Diploid

6 Tijo and Levan

7 Chromosome Size In contrast to other cell organelles, the size of chromosomes shows variation depending on the stages of cell division. Interphase: chromosome are longest & thinnest Prophase: there is a progressive decrease in their length & increase in thickness Anaphase: chromosomes are smallest. Metaphase: Chromosomes are the most easily observed and studied during metaphase when they are very thick. Therefore, chromosomes measurements are generally taken during mitotic metaphase.

8 CHROMOSOME MORPHOLOGY (A T) Telomeres

9 Chromosome Structure Centromere Telomere Short arm Centromere Long arm Metacentric Chromosome Submetacentric Chromosome Acrocentric Chromosome Telocentric Chromosome

10 Centromeres and Telomeres Centromeres and telomeres are two essential features of all eukaryotic chromosomes. Each provide a unique function i.e., absolutely necessary for the stability of the chromosome. Centromeres are required for the segregation of the centromere during meiosis and mitosis. Teleomeres provide terminal stability to the chromosome and ensure its survival

11 Material of the chromosomes The nucleoplasm contains many thread like coiled and elongated structure which take basic stain are called chromatin. Chromatin consists of : 1. (1:1) 2. (1:0.6) 3. (1:0.1)

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13 Euchromatin Portions of chromosomes that stain lightly are only partially condensed, this chromatin is called Euchromatin. It represents most of the chromatin that separate after mitosis. It contains structural genes which replicate and transcribe during G & S1 phase of interphase.

14 Heterochromatin In the dark staining regions, the chromatin remains in the condensed state and is called heterochromatin It is characterized by high content of repititive DNA sequences. It is thought that in the heterochromatin, DNA is tightly packed in the form 30 nm fiber.

15 Heterochromatin has been further classified into two groups: (i) Constitutive (ii) Facultative. Constitutive heterochromatin remains permanently in the heterochromatic stage, i.e., it does not revert to the euchromatic stage. Facultative heterochromatin such type of heterochromatin is not permanently maintained in the condensed state; instead it undergoes periodic dispersal & during this time is transcription ally active. Ex. X-chromosome in the mammalian female.

16 Euchromatin (E) vs Heterochromatin (H) H E DNase Fig. 11 Being more condensed (tightly packed), heterochromatin is resistant to DNase digestion.

17 Chromosomes in eukaryotes Found in the nucleus Condensed and visible during cell division At the beginning of mitosis they can be seen to consist of two threads (sister chromatids) joined by a centromere The sister chromatids are identical copies During mitosis the sister chromatids separate and are placed into two nuclei

18 Bacterial Chromosome Single, circular DNA molecule located in the nucleoid region of cell

19 Chromosomes in eukaryotes and prokaryotes are different PROKARYOTES single chromosome plus plasmids circular chromosome made only of DNA found in cytoplasm copies its chromosome and divides immediately afterwards EUKARYOTES many chromosomes linear chromosomes made of chromatin, a nucleoprotein (DNA coiled around histone proteins) found in a nucleus copies chromosomes, then the cell grows, then goes through mitosis to organise chromosomes in two equal groups

20 Human genome Human genome (in diploid cells) = 6 x 10 9 bp 6 x 10 9 bp X 0.34 nm/bp = 2.04 x 10 9 nm = 2 m/cell Very thin (2.0 nm), extremely fragile Diameter of nucleus = 5-10 mm Most human cells are diploid and each cell contains a total of 2 m of DNA 2 X cells = 2 X meter Total DNA length of 2 X km

21 Compare this with the circumference of the earth (4 X 10 4 km) or (1.5 X 10 8 km) the distance between the earth and the sun. DNA must be packaged to protect it, but must still be accessible to allow gene expression and cellular responsiveness, How?????

22 The major histone proteins Histone Mol. Wt No. of Percentage Amino acid Lys + Arg H1 22, H2A 13, H2B 13, H3 15, H4 11, The DNA double helix is bound to proteins called histones. The histones have positively charged (basic) amino acids to bind the negatively charged (acidic) DNA. Here is an SDS gel of histone proteins, separated by size

23 In addition, chromatin contains an approximately equal mass of a wide variety of non-histone chromosomal proteins. There are more than a thousand different types of these proteins, which are involved in a range of activities, including DNA replication and gene expression. The DNA of prokaryotes is similarly associated with proteins, some of which presumably function as histones do, packing the DNA within the bacterial cell.

24 1 st level 2nd level 3rd level

25 Core DNA

26 Packaging of the DNA in to chromosome has several important functions 1. This compact form fits to inside the cell. 2. It protect DNA from damage. 3. Only chromosomes can transmit efficiently to both daughter cells. 4. Chromosome give the organization to each DNA, this organization facilitates gene expression.

27 Nucleosome core particle

28 individual nucleosomes = beads on a string

29 Detailed analysis of these nucleosome core particles has shown that they contain 146 base pairs of DNA wrapped 1.75 times around a histone core consisting of two molecules each of H2A, H2B, H3, and H4 (the core histones).

30 The Assembly of the Core Histones

31 Notice the long tails of the octamer

32 The bending of DNA in a nucleosome 1. Flexibility of DNAs: A-T riched minor groove inside and G-C riched groove outside 2. DNA bound protein can also help

33 30-nm fiber Flexible linker, DNA binding proteins Structural modulators: H1 histone, ATP-driven Chromatin remodeling machine, covalent modification of histone tails

34 Function & location of Histone H1 It is essential for the second level of chromatin organization.

35 The function of Histone tails

36 Chromatin Remodeling

37 Cyclic Diagram for nucleosome formation and disruption ATP Less tightly bound

38 Covalent Modification of core histone tails Acetylation of lysines Mythylation of lysines Phosphorylation of serines Histone acetyl transferase (HAT) Histone deacetylase (HDAC)

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