Genes are segments of DNA that provide instructions for making proteins. The number and variety of these genes are a direct result of evolutionary processes that allow organisms to adapt and develop new biological traits. Understanding the relationships between genes is paramount for tracing an organism’s evolutionary history and explaining its functional complexity. Paralogs represent a specific class of related genes that are fundamental to how species acquire novel biological capabilities and diversify their molecular toolkits.
What Defines a Paralog
Paralogs are defined as genes found within the same species that have originated from a gene duplication event. These genes belong to a broader category known as homologs, meaning they share a common evolutionary ancestor.
The process of duplication provides a level of genetic redundancy, meaning the organism now possesses two copies of the same functional gene. This new duplicate copy is no longer constrained by the pressure to maintain the original function, freeing it to accumulate mutations over time. This allows the paralog to evolve a new, though often related, function distinct from the original gene, or it may simply become an inactive pseudogene. The existence of these related but distinct genes allows for an expansion of molecular capabilities within a single organism. This mechanism is responsible for the formation of gene families, which are groups of genes that share a common ancestral gene and often perform specialized tasks.
Paralog vs. Ortholog
The distinction between paralogs and orthologs is rooted in the evolutionary event that separated them. Both are types of homologous genes, but they differ based on whether the separation occurred by gene duplication within a single genome or by a speciation event that split a lineage into two separate species.
Paralogs arise from a duplication event, so they exist side-by-side in the same genome and often have related but divergent functions, such as the various subunits of a protein complex. For instance, the genes for human alpha-globin and human beta-globin are paralogs because they arose from an ancient duplication within the vertebrate lineage.
In contrast, orthologs are genes in different species that evolved from a single ancestral gene present in their last common ancestor. Their separation is due to a speciation event, and they generally retain the same biological function in both descendant species. For example, the gene for human alpha-globin and the gene for mouse alpha-globin are orthologs, as they both perform the same oxygen-carrying function and their difference is a result of the human and mouse lineages splitting millions of years ago.
Paralogs represent a divergence of function within a species, while orthologs represent the same function preserved across different species. Comparing orthologs reveals how a gene’s function has been conserved over time, while comparing paralogs shows how function has diversified.
How Gene Duplication Creates Paralogs
Gene duplication is a common occurrence resulting from errors in the cell’s machinery for copying and repairing DNA. One of the most frequent mechanisms is unequal crossing over, which happens during meiosis when homologous chromosomes exchange genetic material. If the chromosomes misalign because of repetitive sequences, the resulting exchange can leave one chromosome with a deletion and the other with a duplicated segment containing an extra gene copy.
Another source of duplication is replication slippage, an error that occurs during DNA replication when the DNA polymerase momentarily detaches and then reattaches to the wrong place on the template strand. Both mechanisms result in two identical copies of a gene initially located near each other in the genome. The immediate consequence of this duplication is genetic redundancy, which shields the duplicate copy from selective pressure. This redundancy allows the duplicate to evolve, as a mutation that might be detrimental in a single-copy gene is tolerated because the original copy continues to perform its normal function.
The Role of Paralogs in Expanding Gene Function
The capacity of paralogs for functional divergence fuels the evolutionary development of complex traits. Once a gene is duplicated, the two copies are free to follow one of two main evolutionary paths: neofunctionalization or subfunctionalization.
Neofunctionalization occurs when one of the gene copies acquires a completely new function through the accumulation of beneficial mutations. This is how entirely new molecular pathways and physiological processes can emerge over vast timescales. The classic example of this functional expansion is the vertebrate globin gene family, which includes myoglobin and various hemoglobin subunits. The ancestral globin gene underwent multiple duplication events, leading to paralogs that specialized in different tasks, such as myoglobin for oxygen storage in muscle and hemoglobin for oxygen transport in the blood.
Subfunctionalization is when the original, broad function of the ancestral gene is partitioned between the two paralogs. This specialization allows for more precise control, with each paralog being expressed in different tissues or at different developmental stages, resulting in a more sophisticated regulation of the original biological process.