34. Speed of DNA replication in mammals is 256 bp/sec, so for replication of 3X10⁹bp DNA it will take a very long time, but it is completed within few hours because

(1) Most of DNA is intron

(2) High amount of Repetitive DNA

(3) Multiple origin of replication

(4) Only small portion is replicated in one cycle

Introduction

Mammalian genomes are large and complex, with approximately 3 billion base pairs (3 × 10^9 bp) to replicate. The replication fork speed in mammals is relatively slow—around 256 base pairs per second—which would theoretically require an impractically long time to duplicate the entire genome if replication occurred from a single origin. However, mammalian cells complete genome replication within a few hours during S phase. This efficiency is primarily due to the presence of multiple origins of replication distributed throughout the genome.

The Challenge of Replicating Large Genomes

• The human genome size (~3 × 10^9 bp) is vast compared to bacterial genomes.

• At a fork speed of 256 bp/sec, a single replication fork would take over 100 days to replicate the entire genome if it started from only one origin.

• Mammalian cells complete replication in roughly 6–8 hours, highlighting the need for a more efficient strategy.

Multiple Origins of Replication: The Key to Speed

• Mammalian chromosomes contain thousands of replication origins spaced across the genome.

• Each origin fires independently, creating multiple replication forks that proceed simultaneously.

• This parallel replication drastically reduces the total time required to duplicate the entire genome.

How Multiple Origins Accelerate Replication

• Simultaneous initiation: Numerous origins activate at different times during S phase, creating replication “bubbles.”

• Shorter replicons: The genome is divided into smaller replicons (units of replication), each replicated by forks emanating from its origin.

• Dynamic regulation: Origin firing is tightly controlled to ensure complete and timely replication without over-replication.

Why Other Options Are Incorrect

1. Most DNA is intron:

   • The presence of introns does not affect replication speed; replication machinery copies all DNA sequences regardless of coding or non-coding status.

2. High amount of repetitive DNA:

   • While repetitive DNA is abundant, it does not inherently speed up replication; it may even pose challenges due to structural complexity.

3. Only a small portion is replicated in one cycle:

   • The entire genome must be replicated each cell cycle; partial replication would lead to genomic instability.

Supporting Evidence from Research

• Studies show replication fork speed varies but is relatively slow (~1–3 kb/min in mammalian cells).

• The number and timing of origin firing compensate for slow fork progression, ensuring complete replication within S phase.

• Origin spacing and fork velocity are coordinated to maintain replication efficiency.

• Early embryonic cells may use even more origins to replicate rapidly during development.

Summary Table

Conclusion

Mammalian cells overcome the slow replication fork speed by utilizing multiple origins of replication distributed throughout their large genomes. This strategy allows simultaneous replication at many sites, completing genome duplication within a few hours despite the inherent speed limitations of individual replication forks.

Correct Answer

(3) Multiple origin of replication