From: veritasium
Inside every human cell, there are six feet of DNA, composed of six billion letters of genetic code [00:00:01]. This DNA is organized into 46 pieces, each 3 to 4 cm long, known as chromosomes [00:00:10]. While often depicted in an X-shape, chromosomes only adopt this form when a cell is preparing to divide; normally, DNA exists as a wiggly thread within the nucleus [00:00:16].
To manage the immense length of DNA (approximately 2 nanometers wide) within a chromosome (centimeters long), the DNA is wrapped around proteins called histones [00:00:26]. These histones possess “wiggly tails” which play a crucial role in gene regulation [00:00:41].
Genetic Makeup and Sex Chromosomes
A unique set of DNA is formed when 23 chromosomes from one parent combine with 23 from the other [00:00:45]. While 22 of these chromosomes from each parent form matching pairs, the 23rd set consists of the sex chromosomes [00:00:53]. Two X chromosomes result in a female, whereas an X and a Y chromosome result in a male [00:00:58].
X Chromosome Inactivation in Females
In males, both sex chromosomes can remain active throughout life [00:01:03]. However, in females, one of the X chromosomes must be inactivated for proper development to occur [00:01:09]. This process of X chromosome inactivation begins when a female embryo is merely four days old and consists of only about 100 cells [00:01:14].
During X chromosome inactivation, one of the two active X chromosomes (one from each parent) is effectively “switched off” [00:01:23]. This silencing is achieved through several molecular mechanisms:
- DNA Packing: The DNA on the inactivated X chromosome is packed more tightly together [00:01:34].
- Histone Modifications: Modifications are made to the “dangly tails” of the histone proteins around which the DNA is wrapped, signaling inactivation [00:01:39].
- Structural Proteins: New structural proteins are added to further bind everything closer together [00:01:45].
- Methyl Groups: Tiny molecular markers called methyl groups are added directly to the DNA, signaling to the cell that this DNA should not be read [00:01:49].
These changes make the DNA on the inactivated X chromosome very difficult for molecular machinery to access, effectively silencing its genes [00:01:56]. In contrast, the active X chromosome’s DNA remains more spread out, allowing better access to its genes [00:02:09]. This accessibility allows RNA polymerase to access and transcribe DNA into messenger RNA, which is then used to make proteins [00:02:37].
Randomness and Inheritance of Inactivation
A surprising aspect of X chromosome inactivation is its apparent randomness: in some cells, the X chromosome from the father wins and remains active, while in others, the mother’s X chromosome prevails [00:02:48]. This results in the 100-cell embryo having a mixture of active X chromosomes [00:02:58]. Crucially, as these cells divide, they maintain the initial active X chromosome choice [00:03:04]. Consequently, all daughter cells will have the same X chromosome activated as their parent cell, continuing into adulthood [00:03:09].
Calico Cats: A Visible Example
While this “stripy pattern” of X chromosome inactivation is not visible in humans, it can be observed in Calico cats [00:03:42]. The gene responsible for coat color in cats is located on the X chromosome [00:03:46]. By examining the pattern of dark and light spots on a Calico cat, one can discern which X chromosome (from the mother or father) has been inactivated in different patches of cells [00:03:51].
This phenomenon also explains why almost all Calico cats are female [00:04:01]. Only female cats can inherit two X chromosomes, each potentially carrying a different coat color gene, allowing for the mosaic pattern that defines a Calico [00:04:05].
Broader Implications of Epigenetics
The inactivation of the X chromosome is a compelling example of epigenetics [00:04:11]. Epigenetics generally refers to mechanisms that turn genes on and off without altering the underlying DNA sequence [00:04:17]. This process is active across all chromosomes, regulating gene expression [00:04:20]. For instance, epigenetics ensures that a pancreatic cell can produce insulin by switching on the insulin gene in that specific cell type, while keeping it switched off elsewhere in the body [00:04:23].
Even more remarkably, epigenetics can be influenced by an individual’s behaviors, and perhaps even by the behaviors of their parents or grandparents [00:04:35]. This means that individuals are not solely a product of their genetic code or DNA, but also a product of their epigenetics, which is shaped by their own actions and those of their ancestors [00:04:47].