The fundamental reason a bacterium cannot successfully read and express human DNA lies in the profound differences between prokaryotic and eukaryotic gene organization and processing. A human gene inserted into a bacterial cell encounters a series of molecular roadblocks, each representing a system the bacterium lacks or fails to recognize. This incompatibility ensures that the human genetic blueprint remains unreadable and ultimately inactive within the simpler bacterial machinery. The sophisticated and compartmentalized nature of human gene expression is simply foreign to the bacterial environment.
Different Transcription Start Signals
The first point of failure for a human gene in a bacterium occurs at the very beginning: transcription initiation. Transcription is the process where the DNA code is copied into a messenger RNA (mRNA) molecule, and it starts at a specific DNA sequence called the promoter. Bacteria and humans use vastly different promoter signals to alert their respective RNA Polymerase (RNAP) enzymes where to begin.
A bacterial promoter is relatively simple, typically consisting of two short, conserved sequences known as the -10 and -35 elements. The bacterial RNAP, guided by a single sigma factor, recognizes this simple structure to initiate RNA synthesis. In contrast, a human gene requires a much more complex and diverse promoter region, often involving elements like the TATA box, the CAAT box, and other distal enhancers.
The bacterial RNAP complex is structurally incapable of efficiently binding to the complex, multi-factor-dependent human promoter. Without the proper recognition signals and the necessary battery of general transcription factors that eukaryotes rely on, the bacterial enzyme usually fails to bind to the human DNA. This results in no, or extremely poor, transcription of the human gene.
The Intron and Exon Structure Barrier
The single greatest structural impediment preventing bacteria from reading human DNA is the presence of non-coding sequences called introns within human genes. Eukaryotic genes are segmented into coding regions called exons, which are interrupted by introns. When a human gene is transcribed, the initial RNA copy, known as pre-mRNA, contains both the exons and the introns.
Prokaryotic genes are continuous, meaning they contain only coding sequences and do not have introns. This difference means that bacterial cells have never developed the molecular machinery necessary to process segmented genes. If a bacterial cell manages to transcribe a human gene, the resulting pre-mRNA transcript will still contain the long, non-coding intron sequences.
To become a functional, mature mRNA, the intron sequences must be precisely cut out, and the remaining exons must be spliced, or joined together, in the correct order. This complex editing process in human cells is carried out by the spliceosome, a massive, intricate molecular machine composed of small nuclear ribonucleoproteins (snRNPs) and numerous proteins. Bacteria do not possess this highly specialized spliceosome structure.
The bacterium lacks the ability to recognize the splice sites and perform the precise cuts and ligations needed to create a continuous coding sequence. Consequently, the resulting bacterial transcript, complete with the non-coding introns, would lead to the production of a non-functional, truncated, or severely misfolded protein. The absence of the spliceosome is the definitive structural reason the human genetic code cannot be interpreted correctly in a prokaryotic environment.
Eukaryotic mRNA Stabilization
Even if the first two hurdles were overcome and a human mRNA molecule appeared in a bacterial cell, it would face a final, rapid destruction. Eukaryotic mRNA molecules are modified with protective elements that stabilize them and signal for translation, modifications that bacteria neither perform nor require. These modifications include the addition of a 5′ cap and a poly-A tail.
The 5′ cap is a chemically modified guanine nucleotide added to the start of the mRNA molecule. This cap serves as a protective helmet against degradation by exonucleases, enzymes that break down RNA from the 5′ end. It also acts as a recognition signal for the ribosome to initiate protein synthesis.
At the other end of the molecule, the poly-A tail, a long chain of adenine nucleotides, is added to the 3′ end. This tail further protects the mRNA from enzymatic degradation and enhances the stability and efficiency of translation.
Since bacterial mRNA naturally lacks these protective structures, the bacterial cell’s environment is rich with enzymes designed to rapidly break down foreign or unprotected RNA. An unmodified human mRNA transcript would be quickly recognized as unstable and destroyed by bacterial exonucleases, ensuring the final step of protein production never successfully begins.