Biology:Orphan gene

From HandWiki
Revision as of 20:40, 10 February 2024 by Scavis2 (talk | contribs) (link)
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)
Short description: Gene that has limited phylogenetic distribution

Orphan genes, ORFans,[1][2] or taxonomically restricted genes (TRGs)[3] are genes that lack a detectable homologue outside of a given species or lineage.[2] Most genes have known homologues. Two genes are homologous when they share an evolutionary history, and the study of groups of homologous genes allows for an understanding of their evolutionary history and divergence. Common mechanisms that have been uncovered as sources for new genes through studies of homologues include gene duplication, exon shuffling, gene fusion and fission, etc.[4][5] Studying the origins of a gene becomes more difficult when there is no evident homologue.[6] The discovery that about 10% or more of the genes of the average microbial species is constituted by orphan genes raises questions about the evolutionary origins of different species as well as how to study and uncover the evolutionary origins of orphan genes.

In some cases, a gene can be classified as an orphan gene due to undersampling of the existing genome space. While it is possible that homologues exist for a given gene, that gene will still be classified as an orphan if the organisms harbouring homologues have not yet been discovered and had their genomes sequenced and properly annotated. For example, one study of orphan genes across 119 archaeal and bacterial genomes could identify that at least 56% were recently acquired from integrative elements (or mobile genetic elements) from non-cellular sources such as viruses and plasmids that remain to be explored and characterized, and another 7% arise through horizontal gene transfer from distant cellular sources (with an unknown proportion of the remaining 37% potentially coming from still unknown families of integrative elements).[7] In other cases, limitations in computational methods for detecting homologues may result in missed homologous sequences and thus classification of a gene as an orphan. Homology detection failure appears to account for the majority, but not all orphan genes.[8] In other cases, homology between genes may go undetected due to rapid evolution and divergence of one or both of these genes from each other to the point where they do not meet the criteria used to classify genes as evidently homologous by computational methods. One analysis suggests that divergence accounts for a third of orphan gene identifications in eukaryotes.[9] When homologous genes exist but are simply undetected, the emergence of these orphan genes can be explained by well-characterized phenomena such as genomic recombination, exon shuffling, gene duplication and divergence, etc. Orphan genes may also simply lack true homologues and in such cases have an independent origins via de novo gene birth, which tends to be a more recent event.[2] These processes may act at different rates in insects, primates, and plants.[10] Despite their relatively recent origin, orphan genes may encode functionally important proteins.[11][12] Characteristics of orphan genes include AT richness, relatively recent origins, taxonomic restriction to a single genome, elevated evolution rates, and shorter sequences.[13]

Some approaches characterize all microbial genes as part of one of two classes of genes. One class is characterized by conservation or partial conservation across lineages, whereas the other (represented by orphan genes) is characterized by evolutionarily instantaneous rates of gene turnover/replacement with a negligible effect on fitness when such genes are either gained or lost. These orphan genes primarily derive from mobile genetic elements and tend to be 'passively selfish', often devoid of cellular functions (which is why they experience little selective pressure in their gain or loss from genomes) but persist in the biosphere due to their transient movement across genomes.[14][15]

History

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 with homologues when more genomes were sequenced.[3] At the time, gene duplication was considered the only serious model of gene evolution[2][4][16] and there were few sequenced genomes for comparison, so a lack of detectable homologues was thought to be most likely due to a lack of sequencing data and not due to a true lack of homology.[3] However, orphan genes continued to persist as the quantity of sequenced genomes grew,[3][17] eventually leading to the conclusion that orphan genes are ubiquitous to all genomes.[2] Estimates of the percentage of genes which are orphans varies enormously between species and between studies; 10-30% is a commonly cited figure.[3]

The study of orphan genes emerged largely after the turn of the century. In 2003, a study of Caenorhabditis briggsae and related species 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.[17] 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."[17]

In 2008, a yeast protein of established functionality, BSC4, was found to have evolved de novo from non-coding sequences whose homology was still detectable in sister species.[18]

In 2009, an orphan gene was discovered to regulate an internal biological network: the orphan gene, QQS, from Arabidopsis thaliana modifies plant composition.[19] The QQS orphan protein interacts with a conserved transcription factor, these data explain the compositional changes (increased protein) that are induced when QQS is engineered into diverse species.[20] 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 "[21]

Identification

Genes can be tentatively classified as orphans if no orthologous proteins can be found in nearby species.[10]

One method used to estimate nucleotide or protein sequence similarity indicative of homology (i.e. similarity due to common origin) is the Basic Local Alignment Search Tool (BLAST). BLAST allows query sequences to be rapidly searched against large sequence databases.[22][23] Simulations suggest that under certain conditions BLAST is suitable for detecting distant relatives of a gene.[24] However, genes that are short and evolve rapidly can easily be missed by BLAST.[25]

The systematic detection of homology to annotate orphan genes is called phylostratigraphy.[26] 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. The term "orphan" is sometimes used only for the youngest phylostratum containing only a single species, but when interpreted broadly as a taxonomically-restricted gene, it can refer to all but the oldest phylostratum, with the gene orphaned within a larger clade.

Homology detection failure accounts for a majority of classified orphan genes.[8] Some scientists have attempted to recover some homology by using more sensitive methods, such as remote homology detection. In one study, remote homology detection techniques were used to demonstrate that a sizable fraction of orphan genes (over 15%) still exhibited remote homology despite being missed by conventional homology detection techniques, and that their functions were often related to the functions of nearby genes at genomic loci.[27]

Sources

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

De novo gene birth

Novel orphan genes continually arise de novo from non-coding sequences.[28] 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. This latter option is supported by research in Drosophila showing that young genes are more likely go extinct.[29]

De novo genes were once thought to be a near impossibility due to the complex and potentially fragile intricacies of creating and maintaining functional polypeptides,[16] but research from the past 10 years or so has found multiple examples of de novo genes, some of which are associated with important biological processes, particularly testes function in animals. De novo genes were also found in fungi and plants.[18][30][31][5][32][33][11][34]

For young orphan genes, it is sometimes possible to find homologous non-coding DNA sequences in sister taxa, which is generally accepted as strong evidence of de novo origin. However, the contribution of de novo origination to taxonomically-restricted genes of older origin, particularly in relation to the traditional gene duplication theory of gene evolution, remains contested.[35][36] Logistically, de novo origination is much easier for RNA genes than protein-coding ones and Nathan H. Lents and colleagues recently reported the existence of several young microRNA genes on human chromosome 21.[37]

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][24] and the evolutionary mechanism by which a gene duplicate could be sequestered and diverge so rapidly remains unclear.[2][38]

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.

Protein characteristics

Orphans genes tend to be very short (~6 times shorter than mature genes), and some are weakly expressed, tissue specific and simpler in codon usage and amino acid composition.[39] Orphan genes tend to encode more intrinsically disordered proteins,[40][41][42] although some structure has been found in one of the best characterized orphan genes.[43] Of the tens of thousands of enzymes of primary or specialized metabolism that have been characterized to date, none are orphans, or even of restricted lineage; apparently, catalysis requires hundreds of millions of years of evolution.[39]

Biological functions

While the prevalence of orphan genes has been established, the evolutionary role of orphans, and its resulting importance, is still being debated. One theory is that many orphans have no evolutionary role; genomes contain non-functional open reading frames (ORFs) that create spurious polypeptide products not maintained by selection, meaning that they are unlikely to be conserved between species and would likely be detected as orphan genes.[3] However, a variety of other studies have shown that at least some orphans are functionally important and may help explain the emergence of novel phenotypes.[2][3][17][19][20][21]

See also

References

  1. ↑ "Finding families for genomic ORFans". Bioinformatics 15 (9): 759–762. September 1999. doi:10.1093/bioinformatics/15.9.759. PMID 10498776. 
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 "The evolutionary origin of orphan genes". Nature Reviews. Genetics 12 (10): 692–702. August 2011. doi:10.1038/nrg3053. PMID 21878963. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 "More than just orphans: are taxonomically-restricted genes important in evolution?". Trends in Genetics 25 (9): 404–413. September 2009. doi:10.1016/j.tig.2009.07.006. PMID 19716618. 
  4. ↑ 4.0 4.1 Evolution by Gene Duplication. Springer Science & Business Media. 2013-12-11. ISBN 978-3-642-86659-3. https://books.google.com/books?id=5SjqCAAAQBAJ. 
  5. ↑ 5.0 5.1 "On the origin of new genes in Drosophila". Genome Research 18 (9): 1446–1455. September 2008. doi:10.1101/gr.076588.108. PMID 18550802. 
  6. ↑ "Origin of primate orphan genes: a comparative genomics approach". Molecular Biology and Evolution 26 (3): 603–612. March 2009. doi:10.1093/molbev/msn281. PMID 19064677. 
  7. ↑ Cortez, Diego; Forterre, Patrick; Gribaldo, Simonetta (2009). "A hidden reservoir of integrative elements is the major source of recently acquired foreign genes and ORFans in archaeal and bacterial genomes" (in en). Genome Biology 10 (6): R65. doi:10.1186/gb-2009-10-6-r65. ISSN 1465-6906. PMID 19531232. 
  8. ↑ 8.0 8.1 "Many, but not all, lineage-specific genes can be explained by homology detection failure". PLOS Biology 18 (11): e3000862. November 2020. doi:10.1371/journal.pbio.3000862. PMID 33137085. 
  9. ↑ "Synteny-based analyses indicate that sequence divergence is not the main source of orphan genes". eLife 9. February 2020. doi:10.7554/eLife.53500. PMID 32066524. 
  10. ↑ 10.0 10.1 "Mechanisms and dynamics of orphan gene emergence in insect genomes". Genome Biology and Evolution 5 (2): 439–455. 2013. doi:10.1093/gbe/evt009. PMID 23348040. 
  11. ↑ 11.0 11.1 "De novo ORFs in Drosophila are important to organismal fitness and evolved rapidly from previously non-coding sequences". PLOS Genetics 9 (10): e1003860. 2013-10-17. doi:10.1371/journal.pgen.1003860. PMID 24146629. 
  12. ↑ "NCYM, a Cis-antisense gene of MYCN, encodes a de novo evolved protein that inhibits GSK3β resulting in the stabilization of MYCN in human neuroblastomas". PLOS Genetics 10 (1): e1003996. January 2014. doi:10.1371/journal.pgen.1003996. PMID 24391509. 
  13. ↑ "Population diversity of ORFan genes in Escherichia coli". Genome Biology and Evolution 4 (11): 1176–87. 2012. doi:10.1093/gbe/evs081. PMID 23034216. 
  14. ↑ "Two fundamentally different classes of microbial genes". Nature Microbiology 2 (3): 16208. November 2016. doi:10.1038/nmicrobiol.2016.208. PMID 27819663. 
  15. ↑ "Evolution of Microbial Genomics: Conceptual Shifts over a Quarter Century". Trends in Microbiology 29 (7): 582–592. July 2021. doi:10.1016/j.tim.2021.01.005. PMID 33541841. 
  16. ↑ 16.0 16.1 "Evolution and tinkering". Science 196 (4295): 1161–1166. June 1977. doi:10.1126/science.860134. PMID 860134. Bibcode: 1977Sci...196.1161J. 
  17. ↑ 17.0 17.1 17.2 17.3 "Orphans as taxonomically restricted and ecologically important genes". Microbiology 151 (Pt 8): 2499–2501. August 2005. doi:10.1099/mic.0.28146-0. PMID 16079329. 
  18. ↑ 18.0 18.1 "De novo origination of a new protein-coding gene in Saccharomyces cerevisiae". Genetics 179 (1): 487–496. May 2008. doi:10.1534/genetics.107.084491. PMID 18493065. 
  19. ↑ 19.0 19.1 "Identification of the novel protein QQS as a component of the starch metabolic network in Arabidopsis leaves". The Plant Journal 58 (3): 485–498. May 2009. doi:10.1111/j.1365-313X.2009.03793.x. PMID 19154206. 
  20. ↑ 20.0 20.1 "QQS orphan gene regulates carbon and nitrogen partitioning across species via NF-YC interactions". Proceedings of the National Academy of Sciences of the United States of America 112 (47): 14734–14739. November 2015. doi:10.1073/pnas.1514670112. PMID 26554020. Bibcode: 2015PNAS..11214734L. 
  21. ↑ 21.0 21.1 "Evolutionary origins of Brassicaceae specific genes in Arabidopsis thaliana". BMC Evolutionary Biology 11 (1): 47. February 2011. doi:10.1186/1471-2148-11-47. PMID 21332978. 
  22. ↑ "Gapped BLAST and PSI-BLAST: a new generation of protein database search programs". Nucleic Acids Research 25 (17): 3389–3402. September 1997. doi:10.1093/nar/25.17.3389. PMID 9254694. 
  23. ↑ "NCBI BLAST homepage". National Center for Biotechnology Information. National Institutes of Health, U.S. Department of Health and Human Services. http://blast.ncbi.nlm.nih.gov/Blast.cgi. 
  24. ↑ 24.0 24.1 "On homology searches by protein Blast and the characterization of the age of genes". BMC Evolutionary Biology 7: 53. April 2007. doi:10.1186/1471-2148-7-53. PMID 17408474. 
  25. ↑ "Phylostratigraphic bias creates spurious patterns of genome evolution". Molecular Biology and Evolution 32 (1): 258–267. January 2015. doi:10.1093/molbev/msu286. PMID 25312911. 
  26. ↑ "A phylostratigraphy approach to uncover the genomic history of major adaptations in metazoan lineages". Trends in Genetics 23 (11): 533–539. November 2007. doi:10.1016/j.tig.2007.08.014. PMID 18029048. 
  27. ↑ "Remote homology and the functions of metagenomic dark matter". Frontiers in Genetics 6: 234. 2015. doi:10.3389/fgene.2015.00234. PMID 26257768. 
  28. ↑ "New genes from non-coding sequence: the role of de novo protein-coding genes in eukaryotic evolutionary innovation". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 370 (1678): 20140332. September 2015. doi:10.1098/rstb.2014.0332. PMID 26323763. 
  29. ↑ "The life cycle of Drosophila orphan genes". eLife 3: e01311. February 2014. doi:10.7554/eLife.01311. PMID 24554240. 
  30. ↑ "Origin and spread of de novo genes in Drosophila melanogaster populations". Science 343 (6172): 769–772. February 2014. doi:10.1126/science.1248286. PMID 24457212. Bibcode: 2014Sci...343..769Z. 
  31. ↑ "Novel genes derived from noncoding DNA in Drosophila melanogaster are frequently X-linked and exhibit testis-biased expression". Proceedings of the National Academy of Sciences of the United States of America 103 (26): 9935–9939. June 2006. doi:10.1073/pnas.0509809103. PMID 16777968. Bibcode: 2006PNAS..103.9935L. 
  32. ↑ "Emergence of a new gene from an intergenic region". Current Biology 19 (18): 1527–1531. September 2009. doi:10.1016/j.cub.2009.07.049. PMID 19733073. 
  33. ↑ "New genes in Drosophila quickly become essential". Science 330 (6011): 1682–1685. December 2010. doi:10.1126/science.1196380. PMID 21164016. Bibcode: 2010Sci...330.1682C. 
  34. ↑ "Extensive natural epigenetic variation at a de novo originated gene". PLOS Genetics 9 (4): e1003437. April 2013. doi:10.1371/journal.pgen.1003437. PMID 23593031. 
  35. ↑ "Evolution: dynamics of de novo gene emergence". Current Biology 24 (6): R238–R240. March 2014. doi:10.1016/j.cub.2014.02.016. PMID 24650912. 
  36. ↑ "Evaluating Phylostratigraphic Evidence for Widespread De Novo Gene Birth in Genome Evolution". Molecular Biology and Evolution 33 (5): 1245–1256. May 2016. doi:10.1093/molbev/msw008. PMID 26758516. 
  37. ↑ Hunter R. Johnson; Jessica A. Blandino; Beatriz C. Mercado; José A. Galván; William J. Higgins; Nathan H. Lents (June 2022). "The evolution of de novo human-specific microRNA genes on chromosome 21". American Journal of Biological Anthropology 178 (2): 223–243. doi:10.1002/ajpa.24504. 
  38. ↑ "The altered evolutionary trajectories of gene duplicates". Trends in Genetics 20 (11): 544–549. November 2004. doi:10.1016/j.tig.2004.09.001. PMID 15475113. 
  39. ↑ 39.0 39.1 "Coming of age: orphan genes in plants". Trends in Plant Science 19 (11): 698–708. November 2014. doi:10.1016/j.tplants.2014.07.003. PMID 25151064. 
  40. ↑ "Elucidating evolutionary features and functional implications of orphan genes in Leishmania major". Infection, Genetics and Evolution 32: 330–337. June 2015. doi:10.1016/j.meegid.2015.03.031. PMID 25843649. 
  41. ↑ "Young Genes are Highly Disordered as Predicted by the Preadaptation Hypothesis of De Novo Gene Birth". Nature Ecology & Evolution 1 (6): 0146–146. June 2017. doi:10.1038/s41559-017-0146. PMID 28642936. 
  42. ↑ "Gene Birth Contributes to Structural Disorder Encoded by Overlapping Genes". Genetics 210 (1): 303–313. September 2018. doi:10.1534/genetics.118.301249. PMID 30026186. 
  43. ↑ "Foldability of a Natural De Novo Evolved Protein". Structure 25 (11): 1687–1696.e4. November 2017. doi:10.1016/j.str.2017.09.006. PMID 29033289. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:Orphan_gene&oldid=3529114"