If hypoxanthine were incorporated into double stranded DNA, which of the following options correctly represents the order of its pairing preference?
(1) Adenine > thymine > guanine > cytosine
(2) Cytosine > adenine > thymine > guanine
(3) Guanine > adenine > thymine > cytosine
(4) Cytosine > thymine > adenine > guanine

Hypoxanthine is a purine derivative found in inosine monophosphate (IMP), a key intermediate in purine nucleotide biosynthesis. When incorporated into DNA, hypoxanthine can pair with natural DNA bases, influencing DNA stability and mutation rates. Understanding its base pairing preferences is essential for insights into mutagenesis, DNA repair, and nucleic acid chemistry.

This article explains the order of base pairing preference of hypoxanthine in double-stranded DNA.

Background: Hypoxanthine in DNA

• Hypoxanthine arises naturally as the deamination product of adenine.

• It is present in nucleotides like inosine and can be incorporated into nucleic acids.

• Hypoxanthine’s ability to pair with multiple bases can lead to mutations if not repaired.

Base Pairing Preferences of Hypoxanthine

• Experimental and computational studies show that hypoxanthine pairs most stably with cytosine (C).

• This pairing mimics the guanine-cytosine (G-C) base pair due to similar hydrogen bonding patterns.

• Hypoxanthine can also pair, though less stably, with adenine (A), thymine (T), and guanine (G).

• The relative order of pairing stability in DNA is:

  Cytosine > Adenine > Thymine > Guanine

• This order is supported by thermodynamic data, molecular dynamics simulations, and biochemical assays.

Implications of Hypoxanthine-Cytosine Pairing

• Hypoxanthine pairing with cytosine can cause A→G transition mutations during DNA replication.

• DNA repair enzymes recognize and remove hypoxanthine to maintain genomic integrity.

• The preferential pairing with cytosine explains the mutagenic potential of adenine deamination.

Summary Table: Hypoxanthine Pairing Preference Order

Conclusion

The correct order of base pairing preference of hypoxanthine incorporated into double-stranded DNA is:

(2) Cytosine > adenine > thymine > guanine

This order reflects the strongest and most biologically relevant base pairing interactions of hypoxanthine, with cytosine being the preferred partner.