Overlapping gene

Overlapping genes are a phenomenon in genetics where a single segment of DNA or RNA contains multiple open reading frames (ORFs) that are capable of being translated into different proteins. These genes overlap in a way that their coding sequences share nucleotides, meaning that the same genetic material can give rise to two or more distinct proteins, depending on the point of initiation of transcription and translation. This concept challenges the traditional view of the genome as a collection of discrete, non-overlapping units of genetic information and highlights the complexity and efficiency of genetic coding.

Overview

Overlapping genes are found in various organisms, including viruses, bacteria, and eukaryotes. They are particularly prevalent in viral genomes, where space is limited, and maximizing the information content of the genetic material is essential for the virus's survival and replication. In viruses, overlapping genes can arise as a result of evolutionary pressures to compact their genomes as much as possible. In more complex organisms, the presence of overlapping genes can contribute to the regulation of gene expression and the generation of protein diversity.

Mechanisms

There are several mechanisms by which overlapping genes can produce multiple proteins from the same DNA sequence. These include:

• Alternative splicing: Different sets of exons are joined together to produce mRNAs that are translated into different proteins.
• Use of alternative start codons: Translation initiation at different AUG codons leads to the production of proteins with different N-terminal sequences.
• Frameshifting: A change in the reading frame during translation, often induced by specific sequence motifs or RNA structures, results in the production of a different protein.
• Leaky scanning: The ribosome skips the first AUG codon and initiates translation at a downstream AUG, producing a protein with a different N-terminal sequence.

Biological Significance

Overlapping genes can have significant biological implications. They can increase the coding capacity of a genome, allowing for a greater number of proteins to be encoded within a limited amount of genetic material. This is particularly important for viruses and other compact genomes. Additionally, overlapping genes can contribute to the regulation of gene expression, as the expression of one gene can influence the expression of the overlapping gene. This can lead to complex regulatory networks that are still not fully understood.

Examples

One well-known example of overlapping genes is found in the HIV genome, where the tat and rev genes overlap. These genes play crucial roles in the virus's life cycle, and their overlapping nature allows for a compact genome that can efficiently encode multiple essential proteins. Another example is the gene for X protein (HBx) in the Hepatitis B virus, which overlaps with the polymerase gene. This arrangement allows the virus to efficiently use its genetic material to produce key proteins for its replication and persistence in the host.

Challenges and Opportunities

The study of overlapping genes presents both challenges and opportunities for researchers. On one hand, the presence of overlapping genes can complicate the annotation of genomes and the prediction of protein-coding regions. On the other hand, understanding how overlapping genes function and are regulated can provide insights into the complexity of genetic coding and regulation, offering opportunities for novel therapeutic interventions.

See Also

• Gene expression
• Genetic code
• Protein biosynthesis
• Viral replication

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  Homo sapiens mtDNA ATP8 and ATP6 Overlap

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  Pavesi 2013 Figure 4

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