14.5: Orthologs and paralogs

When a gene with similar sequences is found in distinct species of organisms, the general assumption is that the gene was present in the species’ common ancestor. In this case, the genes are consider homologous and referred to as orthologs of one another. When a gene is duplicated, in an organism (and in a population) the two versions are termed paralogs of one another and can evolve independently (→). Even more dramatically, entire genomes appear to have been duplicated multiple times during the course of evolution.^[492] In any gene duplication event, the duplicated genes can have a number of fates, they can act as a “back-up” for one another, they can be re-purposed, or one can be lost. Repeated gene duplication events can generate families of evolutionarily-related genes that are recognized by the presence of similar nucleotide and amino acid sequences and structural motifs in the encoded polypeptides. Orthologs are presumed to be derived from a single gene present in the last common ancestor of those species. Paralogous genes are present together in the ancestral organism. If one paralog of a pair is subsequently lost, it can be difficult to distinguish the remaining gene from the original ortholog (NIH LINK).

When paralogs are present in a species, detailed gene/polypeptide sequence comparisons are used to characterize the gene's family tree. The further in the past a gene duplication event occurred, the more mutational noise can obscure the relationship between the duplicated genes. For example, when looking at a DNA sequence there are only four possible bases at each position. A mutation can change a base from an A to a G; a subsequent mutation can change the G back to A. With time, this becomes more and more likely, making it impossible to accurately calculate the number of mutational events that separate the two genes. Many multigene families appear to have originated hundreds of millions or billions of years ago, the older the common ancestor, the more obscure the exact relationship. The exceptions involve genes encoding polypeptides/proteins that are very highly conserved because they are essential and do not tolerate changes. These gene/polypeptide/protein sequences evolve very slowly. In contrast, gene/gene products that are subject to less rigid constraints evolve more rapidly, since more different variants are compatible with life. Speedy evolutionary change complicates using sequence information for determining the relationships between genes found in distantly related organisms. While functional similarities are evidence for evolutionary homology, it is possible, particularly with highly divergent genes and gene products, that they are the result of convergent evolution. As with wings, there may be a different number of ways to carry out a particular molecular/cellular level function.

In an interesting recent set of observations, it appears that genomes contain multiple, previously uncharacterized genes that encode microproteins. Many of these sequences are found in DNA/RNA regions previously thought to be "non-coding". A surprising observation is that many of these microproteins arise rapidly. For example, there appear to be large numbers of microproteins encoding sequences specific to humans, and different from those of other organisms.^[493] Their functional roles can complicate comparisons between model organisms and humans.

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