A paralog is a gene that has originated from a gene duplication event within the genome of a single species. Imagine having two slightly different keys for the same lock; initially, both keys serve the same purpose. Over time, one of these duplicate keys might be modified to open a new, different lock, acquiring a specialized function. This concept of a duplicate gene evolving a new role is fundamental to understanding how organisms develop new biological capabilities.
The Origin of Paralogs
Paralogs arise through gene duplication, which increases the number of gene copies within an organism’s genome. One common mechanism is unequal crossing-over during meiosis, the cell division process that produces reproductive cells. During this event, homologous chromosomes, which carry similar genetic information, can misalign. Instead of an even exchange of genetic material, one chromosome might end up with an extra copy of a gene, while the other receives a deletion.
Another way gene duplication can occur is through retrotransposition, where a messenger RNA (mRNA) molecule is reverse-transcribed back into DNA and then inserted into a new location in the genome. This creates a new gene copy, often lacking the original gene’s regulatory elements.
Distinguishing Paralogs from Orthologs
Understanding paralogs involves distinguishing them from orthologs. The difference lies in the evolutionary event that led to their divergence. Paralogs are genes separated by a duplication event within the same species. For instance, if an ancestral gene in a lineage duplicates, the two resulting copies within that same lineage are paralogs.
Orthologs, on the other hand, are genes in different species that originated from a single gene in their last common ancestor, separated by a speciation event. When an ancestral species splits into two new species, the corresponding gene in each of the descendant species is considered an ortholog. A phylogenetic tree can visually represent this; a node representing a gene duplication within a lineage indicates paralogs, while a node showing the divergence of two species from a common ancestor indicates orthologs. This distinction is important because orthologs generally retain the same function across species, while paralogs frequently evolve new functions.
Evolutionary Fates of Paralogs
Once a gene duplication occurs, the redundant gene copy is no longer under the same selective pressure to maintain its original function, allowing it to evolve. There are several possible evolutionary outcomes for these duplicate genes.
Neofunctionalization
One copy maintains the original function of the ancestral gene, while the other copy accumulates mutations and evolves a completely new function. The evolution of antifreeze proteins in some fish, diverging from a sialic acid synthase gene, serves as a scientific example.
Subfunctionalization
The original functions of the ancestral gene are partitioned between the two duplicate copies. Instead of one gene doing everything, each paralog takes on a subset of the original gene’s roles. This process can lead to the retention of both gene copies because neither alone can fully perform the ancestral function.
Pseudogenization
The duplicate gene copy accumulates mutations that render it non-functional. It becomes a “pseudogene” that is no longer expressed or produces a working protein. This is the most frequent outcome for duplicated genes, as many random mutations are detrimental and can lead to the loss of function.
Paralogs in Human Biology and Disease
Paralogs have contributed to the evolution of human biology, allowing for increased complexity and specialized functions. A prominent example is the human globin gene family, which includes paralogs like alpha-globin, beta-globin, and myoglobin. These genes originated from an ancient ancestral globin gene through successive duplication events. Myoglobin is specialized for oxygen storage in muscles, while the alpha and beta globins combine to form hemoglobin, the protein responsible for oxygen transport in red blood cells throughout the body. This functional diversification arose through neofunctionalization and subfunctionalization, allowing for efficient oxygen management in different tissues.
The presence of multiple paralogs can also have implications for human health. Mutations within these gene families can sometimes lead to genetic disorders. For instance, specific mutations in the alpha-globin genes (HBA1 and HBA2, which are paralogs) can result in various forms of alpha-thalassemia, a condition affecting hemoglobin production. The functional overlap or subtle differences between paralogs mean that disruptions in one copy might be compensated for by another, or conversely, lead to specific disease phenotypes depending on the gene affected and the nature of the mutation.