8/22/2022

Organization of Mammalian Genome.

Introduction:

  • Unlike linear sequences, genomes are more complex.

  • For gene transcription, DNA replication, and DNA repair, nearly two meters of genomic material in every human cell nucleus has to be folded into small spaces

  • It emphasizes the importance of maintaining physical chromosome organization. 

  • Each human has 46 DNA molecules, called chromosomes. 

  • Chromosomes 1 through 22 are numbered consecutively (autosomes), and males and females are differentiated by their sex chromosomes. 

  • There are over 6 billion letters in each of these molecules, and when joined, they would be over 2 meters long

  • To fit inside a nucleus with a diameter of around a micrometer hence the genome must be extensively packaged.

  •  Understanding the relationship between genome structure and function requires a comprehensive understanding of the physical principles and molecular mechanisms underpinning its 3D organization.

  • In this direction, sophisticated microscopy techniques, chromosome conformation capture, and analyses based on polymer models play a critical role. 

  • Resulting from these efforts, we explain the relationship between structure and function at different organizational levels of the genome.

  • Genetic material in an organism is contained in linear DNA sequences called genomes

  • The human genome project had the goal of determining the base pairs that make up human DNA, which comprises 3 billion base pairs. 

  • Although the human genome has produced a wealth of information, it now seems clear that the sequence of DNA base pairs does not determine the cellular function of the genome. A large part of the genome's function lies in its three-dimensional (3D) structure, which consists of meters long DNA enclosed within the limited volume of a cell nucleus of just a few micrometers.

  • A majority of the nucleus volume is taken up by DNA, while cellular factors involved in reading, copying, modifying, and maintaining the genome occupy the remainder

  • A sophisticated pattern in cellular function is derived when genetic information in packaged DNA is accessed by cellular factors that are organized and active in the nucleus of the cell. 

  • A nucleus does not contain transcription, replication, or recombination factories, where transcription, translation, repair, and recombination occur

  • The nucleus of a cell is a complex arrangement of cellular factors responsible for reading, copying, and maintaining genetic information. 

  • RNA-processing factors, transcription factors, and chromatin proteins, among others, are compartmentalized in the nucleus, which directs the activities of transcription and replication. 

  • An elaborate architectural environment within which genomes must act is created by the organizational properties of genomes and the mechanisms that act upon them.

  • A cell's genome functions are organized at three levels of hierarchical organization: nuclear processes themselves, such as transcription, RNA processing, DNA replication, and DNA repair; chromatin organization into higher-order domains; and chromosome orientation within the nucleus. 

  • Each of these levels has regulatory potential, and they are all interconnected. 

  • The spatial compartmentalization of many nuclear processes is a defining characteristic. 

  • Nuclear events do not occur everywhere within the nucleus, but are rather confined to specific locations and usually occur within dedicated nuclear bodies

Commonly Asked Questions

  1. Write a short note on organization of the mammalian genome.

 

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