ecDNA Challenging Genetics Principles | 11 Dec 2024

Source: TH

Why in News?

Recently, a study published in Nature has revealed that extrachromosomal DNA (ecDNA), a previously overlooked component of genetic material, plays a significant role in cancer progression and drug resistance.  

  • These findings challenge the conventional understanding of genetics and open new avenues for understanding and treating cancer. 

What is ecDNA and How It Challenges Conventional Genetic Principles? 

  • About: ecDNA is a type of DNA that exists outside of chromosomes in the nucleus of cells. 
    • DNA stores genetic information crucial for an organism's growth, function, and reproduction. In eukaryotic cells, it is coiled into chromosomes.  
    • Humans have 23 pairs of chromosomes, with genes on them encoding proteins and determining traits. 
  • Formation: ecDNA forms when portions of DNA break away from chromosomes due to processes like chromothripsis (chromosomes are broken and rearranged) or errors in DNA replication, creating circular structures that exist independently within the nucleus. 
  • Significance: ecDNA is commonly found in cancer cells, where it can contain multiple copies of oncogenes, contributing to tumor growth, genetic diversity, and drug resistance. 
  • Challenges to Conventional Law of Genetics: The conventional principles of genetics are primarily based on Mendelian inheritance and the chromosomal theory of inheritance, which is challenged by ecDNA in following ways: 
    • Disruption of Random Gene Distribution:  Traditional genetics holds that genes are distributed randomly and independently during cell division. ecDNA defies this principle by forming clusters of multiple genes that are passed as intact packages, allowing cancer cells to inherit advantageous genetic combinations reliably. 
    • Facilitated Inheritance of Oncogenes: ecDNA clusters often contain oncogenes (genes promoting cancer growth) and other regulatory elements that support tumor survival. This grouping ensures that cancer cells can inherit and amplify beneficial traits in a non-random, purpose-driven manner, enhancing their adaptability and resistance to treatments. 
    • Preservation of Favorable Genetic Combinations: Chromosomes undergo crossing over and recombination during meiosis, leading to genetic diversity. In contrast, ecDNA preserves specific advantageous combinations without recombination, maintaining traits critical for tumor progression. 

ecDNA

How ecDNA Contributes to Cancer and Drug Resistance? 

  • ecDNA can carry multiple copies of oncogenes, leading to increased expression of cancer-promoting genes and tumor growth.  
    • It can take regulatory elements (enhancers) from other parts of the genome, causing abnormal gene activity that promotes cancer. 
  • The non-Mendelian inheritance of ecDNA creates genetic diversity within tumors, complicating targeted treatments. 
  • ecDNA can increase the number of genes that help cancer cells pump out drugs or change their targets, making it harder for chemotherapy to work. 
    • It allows cancer cells to quickly develop new mutations, helping the tumor resist treatment and adapt to drugs. 

Mendel's Laws of Genetics on Inheritance of Traits 

  • Law of Dominance: Dominant traits always express if present; recessive traits appear only when both gene copies are recessive. 
  • Law of Segregation: Each parent passes one gene copy to offspring during gamete formation. 
  • Law of Independent Assortment: Genes for different traits are inherited independently, unless located close on the same chromosome.

UPSC Civil Services Examination Previous Year Question (PYQ) 

Prelim:

Q. Consider the following statements:

  1. Genetic changes can be introduced in the cells that produce eggs or sperms of a prospective parent. 
  2. A person’s genome can be edited before birth at the early embryonic stage. 
  3. Human induced pluripotent stem cells can be injected into the embryo of a pig. 

Which of the statements given above is/are correct?

(a) 1 only 
(b) 2 and 3 only  
(c) 2 only  
(d) 1, 2 and 3 

Ans: (d)