CHROMOSOME

Genetics: From Genes to Genomes (Second Edition)
Hartwell ● Hood ● Goldberg ● Reynolds ● Silver ● Veres
The Prokaryotic Chromosome
The bacterial genome is composed of one circular chromosome
4-5 Mb long
Condenses by supercoiling and looping into a densely packed nucleoid body
Chromosomes replicate inside cell and cell divides by binary fission

Chromosome
Each chromosome has a constriction point called the centromere, which divides the chromosome into two sections, or arms.
The short arm of the chromosome is labeled the p arm. The long arm of the chromosome is labeled the q arm.
Centromere structure and function
Characteristic shapes of chromosomes
Nilai Indeks Sentromer
Nilai Indeks Sentromer
Karyotype
A display of the paired homologues chromosomes from a cell

Allows determination of:
sex of an individual,
abnormal chromosome number,
other chromosome abnormalities,
etc.
A closer look at karyotypes: fully compacted metaphase chromosomes have unique, reproducible banding patterns
Banding patterns are highly reproducible

A closer look at karyotypes: fully compacted metaphase chromosomes have unique, reproducible banding patterns.
Banding patterns help locate genes
A closer look at karyotypes: fully compacted metaphase chromosomes have unique, reproducible banding patterns
Banding patterns can be used to analyze chromosomal differences between species
Can also be used to reveal cause of genetic disease
e.g., Downs syndrome – 3 copies of chromosome 21
Protein components of Chromosomes
Histone proteins abound the chromatin of all eukaryotic cells
Histones – small proteins with basic, positively charged amino acids lysine and arginine
Bind to and neutralize negatively charged DNA
Make up half of all chromatin protein by weight
Five types: H1, H2A, H2B, H3, and H4
Core histones make up nucleosome: H2A, H2B, H3, and H4
DNA and histone synthesis regulation correlate timing so both are synthesized together
High level of similarity of histones among diverse organisms
Protein components of Chromosome
Nonhistone proteins are a heterogeneous group
Half of proteins in chromatin are nonhistone
Large variety of nonhistone proteins – 200 – 2,000,000 in diploid genomes
Large variety of functions
Scaffold – backbone of chromosome
DNA replications – e.g., DNA polymerases
Chromosome segregation – e.g., motor proteins of kinetichores
Transcriptional regulation – largest group regulates transcription during gene expression
Occur in different amounts in different tissues because of variety of function
The nucleosome: The fundamental unit of chromosomal packaging arises from DNAs association with histones
Chromatin fibers with beads having diameter of about 100 A and strings having diameter of 20 A
The nucleosome: The fundamental unit of chromosomal packaging arises from DNAs association with histones
Bead is a nucleosome with about 160 bp of DNA wrapped twice around a core of 8 histones
40 bp of DNA link together nucleosomes
The nucleosome: the fundamental unit of chromosomal packaging arises from DNAs association with histones
X-ray diffraction analysis
DNA does not coil smoothly
Base sequences dictate preferred nucleosome positions along DNA
Spacing and structure affect genetic function
The nucleosome: The fundamental unit of chromosomal packaging arises from DNAs association with histones
Spacing of nucleosomes affects gene expression
Regions between nucleosomes available for interactions with proteins involved in expression, regulation, and further compaction
Determines how and whether certain proteins interact with specific sequences
Packaging into nucleosomes condenses DNA sevenfold
2 meters of DNA shortens to less than 0.25 meters
Models of higher level compaction seek to explain extreme compaction of chromosomes at mitosis
Radial loop-scaffold model for higher levels of compaction
Each loop contains 60-100 kb of DNA tethered (tertambat) by nonhistone scaffold proteins
Radial loop-scaffold model








The Chromosome Theory of Inheritance
Outline of Chromosome Theory of Inheritance
Observations and experiments that placed the hereditary material in the nucleus on the chromosomes
Mitosis ensures that every cell in an organism carries same set of chromosomes
Meiosis distributes one member of each chromosome pair to gamete cells
Gametogenesis, the process by which germ cells differentiate into gametes
Validation of the chromosome theory of inheritance
Evidence that Genes Reside in the Nucleus
1667 – Anton van Leeuwenhoek
Microscopist
Semen contains spermatozoa (sperm animals)
Hypothesized that sperm enter egg to achieve fertilization

1854-1874 – confirmation of fertilization through union of eggs and sperm
Recorded frog and sea urchin fertilization using microscopy and time-lapse drawings and micrographs
Evidence that Genes Reside in Chromosomes
1880s – innovations in microscopy and staining techniques identified thread-like structures
Provided a means to follow movement of chromosomes during cell division
Mitosis – two daughter cells contained same number of chromosomes as parent cell (somatic cells)
Meiosis – daughter cells contained half the number of chromosomes as the parents (sperm and eggs)
One Chromosome Pair Determines an Individual’s Sex
Walter Sutton – Studied great lubber grasshopper
Parent cells contained 22 chromosomes plus an X and a Y chromosome
Daughter cells contained 11 chromosomes and X or Y in equal numbers

Sex chromosome
Provide basis for sex determination
One sex has matching pair
Other sex has one of each type of chromosome

Sex determination in humans
Children receive only an X chromosome from mother but X or Y from father
At Fertilization, Haploid Gametes Produce Diploid Zygotes
Gamete contains one-half the number of chromosomes as the zygote
Haploid – cells that carry only a single chromosome set
Diploid – cells that carry two matching chromosome sets
n – the number of chromosomes in a haploid cell
2n – the number of chromosomes in a diploid cell

diploid vs haploid cell in
Drosophila
melanogaster
The number and shape of chromosomes vary from species to species
Anatomy of a chromosome
Homologous chromosomes match in size, shape, and banding patterns
Homologous chromosomes (homologs) contain the same set of genes
Genes may carry different alleles
Non-homologous chromosomes carry completely unrelated sets of genes


The cell cycle

Maintaining the Chromosome Number
Mitosis ensures that every cell in an organism carries the same chromosomes
Cell cycle – repeating pattern of cell growth and division
Alternates between interphase and mitosis
Interphase – period of cell cycle between divisions/cells grow and replicate chromosomes
G1 – gap phase – birth of cell to onset of chromosome replication/cell growth
S – synthesis phase – duplication of DNA
G2 – gap phase – end of chromosome replication to onset of mitosis
Chromosome replication during S phase of cell cycle
Interphase
Within nucleus
G1, S, and G2 phase – cell growth, protein synthesis, chromosome replication
Outside of nucleus
Formation of microtubules radiating out into cytoplasm crucial for interphase processes
Centrosome – organizing center for microtubules located near nuclear envelope
Centrioles – pair of small darkly stained bodies at center of centrosome in animals (not found in plants)
Mitosis – Sister chromatids separate
Prophase – chromosomes condense
Inside nucleus
Chromosomes condense into structures suitable for replication
Nucleoli begin to break down and disappear
Outside nucleus
Centrosomes which replicated during interphase move apart and migrate to opposite ends of the nucleus
Interphase microtubules disappear and are replaced by microtubules that rapidly grow from and contract back to centrosomal organizing centers
Mitosis - continued
Prometaphase
Nuclear envelope breaks down
Microtubules invade nucleus
Chromosomes attach to microtubules through kinetochore
Mitotic spindle – composed of three types of microtubules
Kinetochore microtubules – centrosome to kinetochore
Polar microtubules – centrosome to middle of cell
Astral microtubules – centrosome to cell’s periphery
Mitosis - continued
Metaphase – middle stage
Chromosomes move towards imaginary equator called metaphase plate
Mitosis - continued
Anaphase
Separation of sister chromatids allows each chromatid to be pulled towards spindle pole connected to by kinetochore microtubule
Mitosis – continued
Telophase
Spindle fibers disperse
Nuclear envelope forms around group of chromosomes at each pole
One or more nucleoli reappear
Chromosomes decondense
Mitosis complete
Mitosis - continued
Cytokinesis - cytoplasm divides
Starts during anaphase and ends in telophase
Animal cells – contractile ring pinches cells into two halves
Plant cells – cell plate forms dividing cell into two halves

The normal cell division
Cell Division in Prokaryotes
MEIOSIS
Meiosis produces haploid germ cells
Somatic cells – divide mitotically and make up vast majority of organism’s tissues
Germ cells – specialized role in the production of gametes
Arise during embryonic development in animals and floral development in plants
Undergo meiosis to produce haploid gametes
Gametes unite with gamete from opposite sex to produce diploid offspring
Meiosis: In The Beginning Two
Humans and many other complex multi-celled organisms incorporate genetic recombination in their reproduction
Reproduction in which there is a re-mixing of the genetic material is called sexual reproduction
Two cells, a sperm and an egg, unite to form a zygote, the single cell from which the organism develops
Meiosis is the process of producing sperm and eggs (gametes)
Gametes Are Haploid
Gametes must have half the genetic material of a normal cell
If the genetic material in the gametes was not halved, when they combined the zygote would have more genetic material than the parents
Meiosis is specialized cell division resulting in cells with half the genetic material of the parents
Gametes have exactly one set of chromosomes, this state is called haploid (1n)
Regular cells have two sets of chromosomes, this state is called diploid (2n)
Stages Of Meiosis
Meiosis resembles mitosis except that it is actually two divisions not one
These divisions are called Meiosis I and Meiosis II
Meiosis I results in haploid cells with chromosomes made up of two chromotids
Meiosis II is essentially mitosis on haploid cells
Stages of meiosis resemble mitosis with two critical differences: the first in prophase I and the second in Metaphase I
Stages Of Meiosis - Meiosis I
Prophase I - The beginning phase -
DNA which was unraveled and spread all over the nucleus is condensed and packaged
Homologous chromosomes (each made of two identical chromatids) come together and form tetrads (4 chromatids)
Crossing over, in which chromatids within tetrads exchange genetic material, occurs
Metaphase I - Middle stage - Tetrads line up along the equator of the cell
Stages Of Meiosis - Meiosis I
Anaphase I - One copy of each chromosome still composed of two chromatids moves to each pole of the cell
Telophase I - End stage - New nuclear membranes are formed around the chromosomes and cytokinesis (cytoplasm division) occurs resulting in two haploid daughter cells
Stages Of Meiosis - Meiosis II
Prophase II - Cells do not typically go into interphase between meiosis I and II, thus chromosomes are already condensed
Metaphase II - Chromosomes line up at the equator of the two haploid cells produced in meiosis I
Anaphase II - Chromosomes made up of two chromatids split to make chromosomes with one chromatid which migrate to the poles of the cells
Telophase II - Cytokinesis and reformation of the nuclear membrane in haploid cells each with one set of chromosomes made of one chromatid
Stages Of Meiosis: Meiosis I
Stages Of Meiosis: Meiosis II
Crossing Over

Gametogenesis involved mitosis and meiosis
Oogenesis – egg formation in humans
Diploid germ cells called oogonia multiply by mitosis to produce primary oocytes
Primary oocytes undergo meiosis I to produce one secondary oocyte and one small polar body (which arrests development)
Secondary oocyte undergoes meiosis II to produce one ovum and one small polar body
Polar bodies disintegrate (=hancur) leaving one large functional gamete
Oogenesis in humans
Gametogenesis
Spermatogenesis in humans
Symmetrical meiotic divisions produce four functional sperm
Begins in male testis in germ cells called spermatogonia
Mitosis produces diploid primary spermatocytes
Meiosis I produces two secondary spermatocytes per cell
Meiosis II produces four equivalent spermatids
Spematids mature into functional sperm
Spermatogenesis in humans
MeiosisChromosomes replicate onceNuclei divide twice

Comparison of Meiosis with Mitosis

Comparison of Meiosis I with Mitosis
Meiosis I:
Prophase I - pairing of homologous chromosomes
Metaphase I – homologous pairs line up at metaphase plate
Anaphase I – homologous chromosomes separate
Telophase I – daughter cells are haploid
Mitosis:
Prophase has no such pairing
Metaphase – chromosomes align at metaphase plate
Anaphase – sister chromatids separate
Telophase – diploid cells
Comparison of Meiosis II with Mitosis




The chromosome theory correlates Mendel’s laws with chromosome behavior during meiosis
Chromosome Behavior
Each cell contains two copies of each chromosome
Chromosome complements appear unchanged during transmission from parent to offspring
Homologous chromosomes pair and then separate to different gametes
Maternal and paternal copies of chromosome pairs separate without regard to the assortment of other homologous chromosome pairs
At fertilization an egg’s set of chromosomes unite with randomly encountered sperm’s chromosomes
In all cells derived from a fertilized egg, one half of chromosomes are of maternal origin, and half are paternal