Integrated Genomic Circuits

Integrated Genomic Circuits

Different genes have regulatory relationships between them i.e. different genes are interlinked with each other through regulatory events.
A set of genes is involved in a circuit. For example, in the case of operons like Lac Operon or Tryp operon.

In Tryp Operon, all 5 genes are connected in such a way that if one fails then all processes will fail.

In the case of prokaryotes, it is more complex.

An integrated genomic circuit, bistable toggles switches are present (On & Off). Apart from the main switch, sub switches are present. The bistable toggle switches are examples of the main switch. Even if sub-circuits are involved having separate genes but if the main switch gets off then the whole process will stop. Subswitches are like genes but one of these genes will be main whose switching on will further activate further genes. A viral infection is a common example of it. A virus either has a lytic cycle or lysogenic. From lysogenic, the cycle is converted to lytic only on a gene’s expression. When lambda phage enters its host then if a gene requiring specific environmental conditions gets on then the lytic cycle will start. If such environmental is not available then the lysogenic cycle will continue. The reason why viruses remain inactivated is because of the one gene which is responsible for the conversion to the lytic cycle.

So in integrated genomic circuits, different genes are completing a process but within these one gene will be such which is controlling the whole process. It can be within different cells & within a single cell as well (Intracellular genomic circuits). Intercellular & intracellular are very large in number but intergenomic is not much.

A force/action is required to go from off to on. Similarly, molecular switches are present in our body that initiate or stop a process. Bistable toggle switches are those which have two stable states. In different networks, one gene will be able to initiate or stop the process by turning on or off. Other genes are also in the state of turning on but on the action is required for their proper turning on. This action is provided by the main gene. In a regulatory network, turning on one gene guarantees the turning of different genes.

Integrated genome circuits are present in different levels of cells and in various organs.

• Product forming from gene b will be called B protein. This product causes inactivation/representation of the C gene.

• C protein also controls the expression of b.

• Another protein A is upregulating both b & c.

• The whole system is an example of a bistable toggle switch.

For turning on 🅰️ is required. If gene coding for 🅰️is active only then 🅰️will form and cause upregulation but B & C are suppressors of each other. It means it is a feedback mechanism i.e contents maintain each other. When 🅰️is present in a sufficient amount or is overexpressed then 🅱️ & C will not get the chance to take over each other as both will be producing more hence they cannot block each other. Then after a certain time, 🅰️will stop producing and both will block each other. 🅰️ can attach to promotors of both at the same time.

In some cases, the situation is more complex as one protein at the same time upregulates one and downregulates the other i.e enhancer for one & repressor for others (either directly or indirectly).

Concept Of Noise:
Error. When talking about the efficiency of a gene or biological function then there will be some noise i.e efficiency is not 100%. This concept is important in bistable toggle switches. For example, when a cell divides into two through mitosis and there are 100 molecules of a transcription factor in the parent cell then according to random probability there should be 50 molecules in each daughter cell. But in actual, division in cells can be variant & diverse: 30-70, 20-80, 51-49 etc. A single transcription factor in various divided cells will have different numbers.

Noises are present in bistable toggle switches as well. Even if switches are off then some current us un sync although no power supply then there will be still some current. In upregulation process, expression is not completely zero but is not enough to perform the function. In some genes, upregulatory mechanisms may not occur throughout life but if they get turned on in a cell then they will express.

There are two types of divisions

1. Random Division
2. Stochastic Division

Due to noise, the division is not random but stochastic i.e biased somewhere less somewhere more.
There are two models for the calculation of noise in a cell or genomic circuit.

1. Binomial Model
2. Normal Model

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