What is a Chromosome?
A chromosome is a long, continuous strand of DNA that contains many genes. Genes function as the basic unit of heredity in living cells, coding for various proteins. Each gene is located at a specific position on the chromosome, known as its locus. Chromosomes also contain non-coding regions of DNA, which are important for regulating gene activity. These regulatory regions include enhancers, promoters, and silencers.
Humans have 23 pairs of chromosomes, for a total of 46 chromosomes. Each parent contributes one chromosome to each pair. The first 22 pairs of chromosomes, called autosomes, look the same in both males and females. The 23rd pair, the sex chromosomes, differ between males and females. Males have one X and one Y chromosome (XY), while females have two X chromosomes (XX).
Structure and Organization
DNA strands consisting of about 150 base pairs are wrapped around positively charged proteins called histones. They are positively charged because they are rich in the positively charged amino acids, arginine, and lysine. The histone complexes are called nucleosomes and they are separated by linker DNA with about 50 base pairs. This structure undergoes further supercoiling to produce chromatids.
There are 5 types of histones i.e., H2A, H2B, H3, and H4 (core histones), and H1 (linker histones). H3 and H4 binds to form an H3-H4 dimer, and H2A and H2B binds to form an H2A-H2B dimer. Two copies of each dimer bind together to form a histone octamer on which the DNA is wrapped. The negative charge of the DNA facilitates strong and stable binding to the octamer. The H1 histone allows for higher-order folding by binding to nucleosomes to convert the DNA from a bead-on-string structure to a coiled tertiary structure called chromatin. The structure of chromosomes varies depending on the stage of the cell cycle. During interphase, chromatin is less tightly condensed and chromosomes are difficult to see under a microscope. During the prophase of mitosis or meiosis, chromatin condenses into chromatids, which can be easily seen under a microscope. At the end of mitosis or meiosis, the chromatids are separated and each becomes a new chromosome in the daughter cells.
In eucaryotes, chromosomes exist in two different forms based on their compaction level, i.e., heterochromatin and euchromatin. Heterochromatin is tightly packed and less accessible to polymerases for replication and transcription, while euchromatin is loosely packed and easily accessible to polymerases. You may use the mnemonic “H” for “hard” to help you remember that the heterochromatin form is hard to replicate and transcribe and “E” to remind you that euchromatin is “easy” to replicate and transcribe. Heterochromatin is further divided into constitutive and facultative. Constitutive means that the heterochromatin is always in that densely packed form and therefore will never be replicated or expressed, while facultative means that it can be unwound to euchromatin.
If the packing state of DNA can be controlled, i.e. wound versus unwound, access to polymerase and hence replication and transcription of genes of interest can be controlled. Various chemical processes can affect the packing state of the DNA. These modifications occur at the n-terminal tails of the histones. They include:
- Acetylation: Addition of an acetyl group to lys or arg residues. Acetylation loosens the DNA making it more accessible for polymerases.
- Methylation: Addition of methyl group to the lys or arg residues. Methylation generally induces a neutral charge, hence increasing packing and restricting transcription. However it may also increase transcription depending on the location of methylation and the degree of methylation (e.g., mono, di, or tri methylation)
- Phosphorylation: Addition of phosphate group on the ser or thr residues. The phosphate group introduces a negative charge that repels the phosphate group on the DNA, making it looser
- ADP ribosylation: Addition of adenosine diphosphate-ribose (ADP-ribose). ADP-ribose imparts a negative charge repulsion between the histone and DNA, causing the DNA to loosen.
Histone modification is a basis for epigenetics (“above genetics”) in which gene expression is modified by influences outside of the genetic code. It may be argued that while DNA is the hardware, histone modification/tagging is the software, telling DNA what to do. That is, when and when not to transcribe. Various lifestyle practices may affect how the DNA is tagged such as food, drugs, toxins, physical activity, and psychological stress. These modifications may be passed down to the next generation.