Orphan gene

Orphan genes (also called ORFans, especially in microbial literature)^[1][2] are genes without homologues in other lineages.^[2] Orphans are a subset of taxonomically-restricted genes (TRGs), which are unique to a specific taxonomic level (e.g. plant-specific).^[3] In contrast to non-orphan TRGs, orphans are usually considered unique to a very narrow taxon, generally a species.

The classic model of evolution is based on duplication, rearrangement, and mutation of genes with the idea of common descent.^[4][5] Orphan genes differ in that they are lineage-specific with no known history of shared duplication and rearrangement outside of their specific species or clade.^[6] Orphan genes may arise through a variety of mechanisms, such as horizontal gene transfer, duplication and rapid divergence, and de novo origination,^[2] and may act at different rates in insects, primates, and plants.^[7] Despite their relatively recent origin, orphan genes may encode functionally important proteins.^[8][9]

Definition

In order to be considered an orphan gene, the gene must be encoding a protein that lacks homology to any predicted peptide from other genomes of similar species.^[7] Orphans are a subset of taxonomically-restricted genes (TRGs), which are unique to a specific taxonomic level (e.g. plant-specific).^[3] In contrast, orphans are usually considered unique to a very narrow taxon, generally a species.

History of orphan genes

Orphan genes were first discovered when the yeast genome-sequencing project began in 1996.^[2] Orphan genes accounted for an estimated 26% of the yeast genome, but it was believed that these genes could be classified when more genomes were sequenced.^[3] Since there are between an estimated 1 and 20 million animal species in the world, the discovery was ignored for some time.^[10] However, the cumulative number of orphan genes in sequenced genomes did not level off as time passed.^[11] In the sequencing of Schizosaccharomyces pombe and Schizosaccharomyces cerevisiae in 2002, researchers found that 14 percent and 19 percent, respectively, of the protein encoding genes were totally unique to that specific species.^[3] Unfortunately for the study of orphan genes, researchers were more interested in studying the similar gene sequences and not the unknown regions.^[3]

It was not until 2003 that orphan genes were directly accessed. In a study of Caenorhabditis briggsae and related species, researchers compared over 2000 genes.^[3] They proposed that these genes must be evolving too quickly to be detected and are consequently sites of very rapid evolution.^[3] In 2005, Wilson examined 122 bacterial species to try to examine whether the large number of orphan genes in many species was legitimate.^[11] The study found that it was legitimate and played a role in bacterial adaptation. The definition of taxonomically-restricted genes was introduced into the literature to make orphan genes seem less “mysterious.”^[11]

In 2009, a study went into “‘the dark matter of protein space’’ to analyze the 2,200 domains of unknown function and concluded that they facilitated evolution of novel functions.^[12] This was important because orphan genes were recognized to have a purpose at the level of proteins.

In 2011, a comprehensive genome-wide study of the extent and evolutionary origins of orphan genes in plants was conducted in the model plant Arabidopsis thaliana ”^[13]

Estimates of the percentage of genes which are orphans varies enormously between species and between studies; 10-30% is a commonly cited figure.^[3]

How to identify orphan genes

Genes can be tentatively classified as orphans if no orthologous proteins can be found in nearby species.^[7]

One method used to estimate nucleotide or protein sequence similarity is the Basic Local Alignment Search Tool (BLAST). BLAST allows query sequences to be rapidly searched against large sequence databases.^[14][15] Simulations suggest that under certain conditions BLAST is suitable for detecting distant relatives of a gene.^[16] However, genes that are short and evolve rapidly can easily be missed by BLAST.^[17]

Another method utilized to detect orphan genes is called phylostratigraphy.^[18] Phylostratigraphy generates a phylogenetic tree in which the homology is calculated between all genes of a focal species and the genes of other species. The earliest common ancestor for a gene determines the age, or phylostratum, of the gene. Although phylostratigraphy is typically utilized to infer gene/protein age, it can easily be used to detect orphan genes. If an orphan gene is defined as being unique to one species, then orphan genes are those genes located within the highest phylostratum (i.e., those possessing homologs only in the focal species). However, if one chooses to define an "orphan gene" as being unique to an entire clade (not just a single branch), then orphan genes would include all those genes found within the range of phylostrata comprising the clade.

Where do orphan genes come from?

Orphan genes arise from multiple sources, predominantly through de novo origination, duplication and rapid divergence, and horizontal gene transfer.^[2]

De Novo Origination

Novel orphan genes continually arise de novo from non-coding sequences.^[19] These novel genes may be sufficiently beneficial to be swept to fixation by selection. Or, more likely, they will fade back into the non-genic background. That young genes are more likely to go extinct (become pseudogenes) has recently been confirmed in Drosophila.^[20]

Duplication and Divergence

The duplication and divergence model for orphan genes involves a new gene being created from some duplication or divergence event and undergoing a period of rapid evolution where all detectable similarity to the originally duplicated gene is lost.^[2] While this explanation is consistent with current understandings of duplication mechanisms,^[2] the number of mutations needed to lose detectable similarity is large enough as to be a rare event,^[2][16] and the evolutionary mechanism by which a gene duplicate could be sequestered and diverge so rapidly remains unclear.^[2][21]

Horizontal Gene Transfer

Another explanation for how orphan genes arise is through a duplication mechanism called horizontal gene transfer, where the original duplicated gene derives from a separate, unknown lineage.^[2] This explanation for the origin of orphan genes is especially relevant in bacteria and archaea, where horizontal gene transfer is common. At least in bacteria, there is no correlation between organism complexity and orphan genes percentage.^[22] Likewise, in bacteria, there is no correlation between orphan percentage and genome length.^[22]

Protein characteristics

Orphans genes tend to be very short (~6 times shorter than mature genes), weakly expressed, tissue specific and simple in codon usage and amino acid composition.^[23] Orphan genes mostly encode intrinsically disordered proteins.^[24]

Biological functions

Some researchers have proposed that orphan genes drive morphological specification because they allow organisms to "adapt to constantly changing ecological conditions."^[3] These all give more possibilities of differences within a population to help it survive in its environment, which can be helpful if it recently experienced a bottleneck.^[2]

References

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