Paralog genes are copies of an existing gene within a single organism, created by a duplication event. At some point in a species’ evolutionary history, this copying leads to two versions existing in the genome where there was once only one. These paralogs are initially identical but can accumulate different mutations over time. This process allows for the development of new gene functions while the original is preserved, making paralogs a source of genetic innovation.
The Process of Gene Duplication
Paralogous genes are created by gene duplication, which happens through several mechanisms, often as errors during cellular processes. One common cause is unequal crossing-over during meiosis, where homologous chromosomes misalign when they exchange genetic material.
This misalignment results in an unequal trade of DNA. One chromosome ends up with a duplicated segment containing a gene, while its partner chromosome loses that same segment. The result for the first chromosome is an extra copy of a gene where only one existed before.
Another way duplication can happen is through replication slippage, an error during the normal copying of DNA. In this process, the enzyme DNA polymerase can momentarily detach from the DNA strand it is reading. When it reattaches, it may slip and re-read a section it has already copied, resulting in a duplicated sequence.
Evolutionary Pathways for Paralog Genes
After duplication, the two paralogs can evolve differently because one functional copy acts as a safety net. This redundancy allows one copy to accumulate mutations without harming the organism, as the other performs the original function. The duplicated gene can follow one of three primary evolutionary paths.
One outcome is neofunctionalization, where one paralog maintains the original function while the second copy acquires mutations that give it a new role. This allows for the creation of novel biological capabilities without losing existing ones. The new function may be related to the original or something entirely different, providing a path for organisms to adapt to new environments.
Another possibility is subfunctionalization, where both copies accumulate mutations that degrade parts of their original function. Each paralog becomes specialized in performing a distinct sub-task of the ancestral gene’s role. Together, the two specialized genes are required to carry out the complete, original function, effectively partitioning the labor between them.
The final path is nonfunctionalization, or pseudogenization. One copy accumulates mutations that render it non-functional, perhaps by preventing it from being read or by creating a non-working protein. Since the other copy is still active, this loss is often not detrimental. The inactive copy becomes a “pseudogene” that no longer contributes to the organism’s biology.
Paralogs Versus Orthologs
To understand gene evolution, it is useful to distinguish between paralogs and orthologs. Both describe relationships between similar genes, but they have different origins based on the evolutionary event that created them: gene duplication versus speciation.
Paralogs are genes within a single species that arose from a duplication event. Orthologs, on the other hand, are genes found in different species that evolved from a single ancestral gene in a common ancestor.
The human globin gene family provides a clear example. The alpha-globin and beta-globin genes in humans are paralogs, as they arose from a duplication event. In contrast, the human alpha-globin gene and the chimpanzee alpha-globin gene are orthologs, tracing back to the same gene in their common ancestor.
Understanding this distinction is important for studying evolutionary history. Paralogs reveal how gene families expand and give rise to new functions within a lineage. Orthologs are used to trace evolutionary relationships between species and understand how biological processes are conserved or diverge.
The Impact of Paralogs on Organisms
The duplication and divergence of paralogous genes have allowed for greater biological complexity. Gene families, which are groups of related paralogs, underpin many physiological processes. The globin gene family in humans is a clear example of how paralogs facilitate specialized functions.
The ancestral globin gene, responsible for binding oxygen, duplicated and gave rise to several paralogs over evolutionary time. This diversification led to myoglobin and the various subunits of hemoglobin. Myoglobin is specialized for oxygen storage within muscle cells, while hemoglobin transports oxygen in the blood, picking it up in the lungs and delivering it throughout the body.
Different hemoglobin paralogs are expressed at different stages of human development. For instance, fetal hemoglobin has a higher affinity for oxygen than adult hemoglobin, allowing a fetus to draw oxygen from the mother’s bloodstream. This fine-tuned regulation, made possible by having multiple paralogous genes, shows their significance. The evolution of this gene family enabled vertebrates to become larger, more active organisms.
While paralogs are a source of evolutionary novelty, their misregulation or mutation can be associated with disease. Since paralogs often have similar structures, errors in their regulation can lead to imbalances in biological pathways. Studying these gene families provides insights into both evolutionary history and the genetic basis of certain conditions.