CHROMOSOME – WHAT IS IT, ITS COMPONENTS, STRUCTURE AND ORGANIZATION

A chromosome is a structure made by condensation of DNA found in nucleus of a cell that carries genetic material of an organism.

The DNA of a eukaryotic organism gets highly condensed within the nucleus of cell to form chromosome. Chromosomes first appear during prophase stage of cell division. They become even more distinct with characteristic X shape during metaphase. During metaphase, chromosome is almost completely transcriptionally inactive. When the cell is not dividing, chromosomes appear as loose strands inside the nucleus.

Humans possess 23 pairs of chromosomes : 22 pairs of autosomes and one pair of sex chromosome ( XX for females and XY for males).

A condensed form of DNA in the form of chromosome is required to fit the genetic material in a compact manner so that genetic information can be duplicated easily during cell division.

STRUCTURE OF CHROMOSOME

Chromosome is the condensed form of chromatin. Chromatin consists of nucleosome ( DNA wrapped around octamer of histone protein ) along with few non histone proteins and small quantity of RNA.

A typical metaphase chromosome shows :

• SISTER CHROMATIDS – Two identical strands of chromosome connected by a centromere in X shape manner.
• CENTROMERE – The constricted portion of a chromosome which attaches sister chromatids. Centromere is an adenine-thymine ( A-T ) rich region containing repeat sequences of DNA varying in size from 10² to 10⁶ base pairs. It contains CENP-A protein (H₃ histone variant) and other centromere binding proteins. This complex called kinetochore acts as the anchor for the spindle fiber during mitosis to segregate chromosomes.
• ARMS – The centromere divides a chromosome into two arms. The short arm is the ‘p’ arm and longer arm is the ‘q’ arm.
• TELOMERE – The ends of chromosome consists of repeat sequences of TG. In humans, telomere shows variable number of repeats of 5′-TTAGGG-3′ . Since last few bases are not copied during each round of DNA replication, telomere ensures that the ends of replicated DNA does not shorten so much that genetic information starts getting eroded. Telomerase is an enzyme that synthesizes telomere and thus maintains adequate length of telomere. Shortening of telomere can be harmful as it can lead to malignant transformation and aging. Telomerase is a target for cancer chemotherapy and drug development.

TYPES OF CHROMOSOME

There are four types of chromosomes based on the location of centromere :

• METACENTRIC – Centromere is located in the middle such that there are two equal arms of chromosome.
• SUBMETACENTRIC – Centromere is a little away from center forming a long arm and a short arm.
• ACROCENTRIC – Centromere is further away from center leading to formation of a very long arm and a very short arm.
• TELOCENTRIC – Centromere is located at the terminal end of chromosome.

ORGANIZATION OF CHROMOSOME

Chromatin fibers form the basic unit of chromosome. Chromatin consists of nucleosome and nucleosomes are made up of DNA and proteins. The length of double stranded DNA in each chromosome is around 1000 times the diameter of nucleus of cell.

NUCLEOSOME

Nucleosomes are made up of DNA segments wound around eight histone protein molecules ( histone octamer ).

HISTONES –

Histones are proteins that are basic in nature. They are rich in lysine and arginine. Nucleosomes contain four major types of histones – H₂A , H₂B , H₃ and H₄ . These are known as core histones.

Histone octamer is composed of two tetramers : ( H₃ – H₄ )₂ and ( H₂A – H₂B )₂ . In the nucleosome, the DNA is supercoiled in a left – handed helix over the surface of the disc shaped histone octamer. Assembly of nucleosome is mediated by proteins known as chaperones.

DNA is coiled 1.75 times over histone octamer in the form of super helical turns. About 145 base pairs of DNA are in contact with histone octamer. Core particles are separated by 30 base pair region of DNA known as linker.

Histones serve to condense the DNA. It is also important for gene regulation and molecular interactions of DNA.

The appearance of nucleosomes resembles ‘beads on a string‘ when seen under an electron microscope.

Apart from disc like nucleosome, there are higher order structures such as 10 nm fibril, 30 nm fibril and 300 nm fiber which are formed by further supercoiling of nucleosomes.

CHROMATIN

Chromatin is composed of double stranded DNA, histones, few non histone proteins and small quantity of RNA.

During interphase, chromatin fibers appear to be organized into 30,000 to 1,00,000 base pair loops or domains.

A 30 nm chromatin fiber has to be compacted in length a hundred times in order to form a mitotic chromosome.

Heterochromatin is inactive transcriptionally. It is densely packed and stains dark.

Constitutive heterochromatin, found near centromere and telomere is always condensed and always inactive.

Facultative heterochromatin is sometimes condensed and inactive but can be actively transcribed at other times. One of the X chromosome of mammalian female is a facultative heterochromatin. It becomes transcriptionally active only during gametogenesis.

Euchromatin is transcriptionally active chromatin. It is loosely packed and takes up light stain.

FUNCTIONS OF CHROMOSOME

• Chromosomes store genetic information as they contain tightly packed DNA.
• Chromosomes protect DNA from damage.
• They store genetic information in a compact manner so that during cell division, each daughter cell gets complete set of genetic information.
• Regulate gene expression.
• Responsible for sex determination ( XX in females and XY in males).
• Chromosomes form the basis of heredity by passing genetic traits from parents to their offspring.