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Cited by 51Genomics and Phylogenetic StudiesChromosomal and Genetic VariationsFractal and DNA sequence analysis

Protein length distribution is remarkably uniform across the tree of life

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Nevers, Yannis, Glover, Natasha M., Dessimoz, Christophe, Lecompte, Odile·2023·Genome Biology
DOI 10.1186/s13059-023-02973-2PMC PMC10251718

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Abstract

Background: In every living species, the function of a protein depends on its organization of structural domains, and the length of a protein is a direct reflection of this. Because every species evolved under different evolutionary pressures, the protein length distribution, much like other genomic features, is expected to vary across species but has so far been scarcely studied. Results: Here we evaluate this diversity by comparing protein length distribution across 2326 species (1688 bacteria, 153 archaea, and 485 eukaryotes). We find that proteins tend to be on average slightly longer in eukaryotes than in bacteria or archaea, but that the variation of length distribution across species is low, especially compared to the variation of other genomic features (genome size, number of proteins, gene length, GC content, isoelectric points of proteins). Moreover, most cases of atypical protein length distribution appear to be due to artifactual gene annotation, suggesting the actual variation of protein length distribution across species is even smaller. Conclusions: These results open the way for developing a genome annotation quality metric based on protein length distribution to complement conventional quality measures. Overall, our findings show that protein length distribution between living species is more uniform than previously thought. Furthermore, we also provide evidence for a universal selection on protein length, yet its mechanism and fitness effect remain intriguing open questions.

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  • Exon lengths are highly conserved due to functional constraints on protein-coding sequences.

    “While exon lengths are highly conserved due to functional constraints on protein-coding sequences (95–97)”

    From Convergent genome streamlining accompanies independent miniaturization in the world’s smallest fishes (2026) · cites this paper as [96]

    The Conclusions report consistent protein-length distributions across species, and the Discussion suggests selective pressure on protein length. Neither passage establishes that exon lengths are conserved or that functional constraints cause their conservation. A search for exon-length conservation found no passage addressing that claim. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

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  1. [1]Wright SI. Evolution of Genome Size [Internet]. eLS. Chichester, UK: John Wiley & Sons, Ltd; 2017. p. 1–6. Available from: 10.1002/9780470015902.a0023983 · DOI
  2. [2]Elliott TA Gregory TR What’s in a genome? The C-value enigma and the evolution of eukaryotic genome content Philos Trans R Soc Lond B Biol Sci 2015 370 20140331 10.1098/rstb.2014.0331 26323762 PMC4571570 · DOI · Paper page
  3. [3]Li X-Q Du D Variation, evolution, and correlation analysis of C+G content and genome or chromosome size in different kingdoms and phyla PLoS ONE 2014 9 e88339 10.1371/journal.pone.0088339 24551092 PMC3923770 · DOI
  4. [4]Kiraga J Mackiewicz P Mackiewicz D Kowalczuk M Biecek P Polak N The relationships between the isoelectric point and: length of proteins, taxonomy and ecology of organisms BMC Genomics 2007 8 163 10.1186/1471-2164-8-163 17565672 PMC1905920 · DOI
  5. [5]Kozlowski LP Proteome-pI: proteome isoelectric point database Nucleic Acids Res 2017 45 D1112 D1116 10.1093/nar/gkw978 27789699 PMC5210655 · DOI
  6. [6]Yandell M Mungall CJ Smith C Prochnik S Kaminker J Hartzell G Large-scale trends in the evolution of gene structures within 11 animal genomes PLoS Comput Biol 2006 2 e15 10.1371/journal.pcbi.0020015 16518452 PMC1386723 · DOI
  7. [7]Rogozin IB Carmel L Csuros M Koonin EV Origin and evolution of spliceosomal introns Biol Direct 2012 7 11 10.1186/1745-6150-7-11 22507701 PMC3488318 · DOI
  8. [8]Falb M Pfeiffer F Palm P Rodewald K Hickmann V Tittor J Living with two extremes: conclusions from the genome sequence of Natronomonas pharaonis Genome Res 2005 15 1336 1343 10.1101/gr.3952905 16169924 PMC1240075 · DOI
  9. [9]Kennedy SP Ng WV Salzberg SL Hood L DasSarma S Understanding the adaptation of Halobacterium species NRC-1 to its extreme environment through computational analysis of its genome sequence Genome Res 2001 11 1641 1650 10.1101/gr.190201 11591641 PMC311145 · DOI
  10. [10]Oliver JL Marín A A relationship between GC content and coding-sequence length J Mol Evol 1996 43 216 223 10.1007/BF02338829 8703087 · DOI
  11. [11]Middleton S Song T Nayak S Length constraints of multi-domain proteins in metazoans Bioinformation 2010 4 441 444 10.6026/97320630004441 20975906 PMC2951704 · DOI
  12. [12]Lipman DJ Souvorov A Koonin EV Panchenko AR Tatusova TA The relationship of protein conservation and sequence length BMC Evol Biol 2002 2 20 10.1186/1471-2148-2-20 12410938 PMC137605 · DOI
  13. [13]Zhang J Protein-length distributions for the three domains of life Trends Genet 2000 16 107 109 10.1016/S0168-9525(99)01922-8 10689349 · DOI · Paper page
  14. [14]Jain R Ramakumar S Stochastic dynamics modeling of the protein sequence length distribution in genomes: implications for microbial evolution Physica A 1999 273 476 485 10.1016/S0378-4371(99)00370-2 · DOI
  15. [15]Xu L Chen H Hu X Zhang R Zhang Z Luo ZW Average gene length is highly conserved in prokaryotes and eukaryotes and diverges only between the two kingdoms Mol Biol Evol 2006 23 1107 1108 10.1093/molbev/msk019 16611645 · DOI
  16. [16]Brocchieri L Karlin S Protein length in eukaryotic and prokaryotic proteomes Nucleic Acids Res 2005 33 3390 3400 10.1093/nar/gki615 15951512 PMC1150220 · DOI · Paper page
  17. [17]Tiessen A Pérez-Rodríguez P Delaye-Arredondo LJ Mathematical modeling and comparison of protein size distribution in different plant, animal, fungal and microbial species reveals a negative correlation between protein size and protein number, thus providing insight into the evolution of proteomes BMC Res Notes 2012 5 85 10.1186/1756-0500-5-85 22296664 PMC3296660 · DOI
  18. [18]Altenhoff AM Train C-M Gilbert KJ Mediratta I Mendes de Farias T Moi D OMA orthology in, website overhaul, conserved isoforms, ancestral gene order and more Nucleic Acids Res 2021 2021 49 D373 D379 10.1093/nar/gkaa1007 PMC7779010 33174605 · DOI
  19. [19]Hug LA Baker BJ Anantharaman K Brown CT Probst AJ Castelle CJ A new view of the tree of life Nat Microbiol 2016 1 16048 10.1038/nmicrobiol.2016.48 27572647 · DOI · Paper page
  20. [20]Clavel J Escarguel G Merceron G Mv morph: An r package for fitting multivariate evolutionary models to morphometric data Methods Ecol Evol Wiley 2015 6 1311 1319 10.1111/2041-210X.12420 · DOI
  21. [21]Niimura Y Nei M Extensive gains and losses of olfactory receptor genes in mammalian evolution PLoS ONE 2007 2 e708 10.1371/journal.pone.0000708 17684554 PMC1933591 · DOI
  22. [22]Clarke KR. Non-parametric multivariate analyses of changes in community structure. Aust J Ecol. John Wiley & Sons, Ltd; 1993;18:117–43.
  23. [23]McCoy MJ Fire AZ Intron and gene size expansion during nervous system evolution BMC Genomics 2020 21 360 10.1186/s12864-020-6760-4 32410625 PMC7222433 · DOI
  24. [24]Moran-Reyna A Coker JA The effects of extremes of pH on the growth and transcriptomic profiles of three haloarchaea F1000Res 2014 3 168 10.12688/f1000research.4789.2 25285207 PMC4176423 · DOI
  25. [25]Seppey M Manni M Zdobnov EM BUSCO: assessing genome assembly and annotation completeness Methods Mol Biol 2019 1962 227 245 10.1007/978-1-4939-9173-0_14 31020564 · DOI
  26. [26]UniProt Consortium UniProt: the universal protein knowledgebase in 2021 Nucleic Acids Res 2021 49 D480 D489 10.1093/nar/gkaa1100 33237286 PMC7778908 · DOI · Paper page
  27. [28]Wang D Hsieh M Li W-H A general tendency for conservation of protein length across eukaryotic kingdoms Mol Biol Evol 2005 22 142 147 10.1093/molbev/msh263 15371528 · DOI
  28. [29]Zhuang Y Ma F Li-Ling J Xu X Li Y Comparative analysis of amino acid usage and protein length distribution between alternatively and non-alternatively spliced genes across six eukaryotic genomes Mol Biol Evol 2003 20 1978 1985 10.1093/molbev/msg203 12885959 · DOI
  29. [30]Rebeaud ME, Mallik S, Goloubinoff P, Tawfik DS. On the evolution of chaperones and co-chaperones and the exponential expansion of proteome complexity [Internet]. bioRxiv. 2020:2020.06.08.140319. Available from: https://www.biorxiv.org/content/10.1101/2020.06.08.140319v1.full. Cited 14 Apr 2021. · DOI
  30. [31]Wakaguri H Suzuki Y Sasaki M Sugano S Watanabe J Inconsistencies of genome annotations in apicomplexan parasites revealed by 5’-end-one-pass and full-length sequences of oligo-capped cDNAs BMC Genomics 2009 10 312 10.1186/1471-2164-10-312 19602295 PMC2722674 · DOI
  31. [32]Seliverstov AV Zverkov OA Istomina SN Pirogov SA Kitsis PS Comparative analysis of apicoplast-targeted protein extension lengths in apicomplexan parasites Biomed Res Int 2015 2015 452958 10.1155/2015/452958 26114107 PMC4465681 · DOI
  32. [33]Blackman MJ Bannister LH Apical organelles of Apicomplexa: biology and isolation by subcellular fractionation Mol Biochem Parasitol 2001 117 11 25 10.1016/S0166-6851(01)00328-0 11551628 · DOI
  33. [34]Li H Child MA Bogyo M Proteases as regulators of pathogenesis: examples from the Apicomplexa Biochim Biophys Acta 2012 1824 177 185 10.1016/j.bbapap.2011.06.002 21683169 PMC3232290 · DOI
  34. [35]Silmon de Monerri NC Flynn HR Campos MG Hackett F Koussis K Withers-Martinez C Global identification of multiple substrates for Plasmodium falciparum SUB1, an essential malarial processing protease Infect Immun 2011 79 1086 9 10.1128/IAI.00902-10 21220481 PMC3067499 · DOI
  35. [36]Su M Ling Y Yu J Wu J Xiao J Small proteins: untapped area of potential biological importance Front Genet 2013 4 286 10.3389/fgene.2013.00286 24379829 PMC3864261 · DOI
  36. [37]Frith MC Forrest AR Nourbakhsh E Pang KC Kai C Kawai J The abundance of short proteins in the mammalian proteome PLoS Genet 2006 2 e52 10.1371/journal.pgen.0020052 16683031 PMC1449894 · DOI
  37. [38]Simão FA Waterhouse RM Ioannidis P Kriventseva EV Zdobnov EM BUSCO: assessing genome assembly and annotation completeness with single-copy orthologs Bioinformatics 2015 31 3210 3212 10.1093/bioinformatics/btv351 26059717 · DOI · Paper page
  38. [39]Ye Z Xu S Spitze K Asselman J Jiang X Ackerman MS A New Reference Genome Assembly for the Microcrustacean Daphnia pulex G3 2017 7 1405 1416 10.1534/g3.116.038638 28235826 PMC5427498 · DOI
  39. [40]Florea L Souvorov A Kalbfleisch TS Salzberg SL Genome assembly has a major impact on gene content: a comparison of annotation in two Bos taurus assemblies PLoS ONE 2011 6 e21400 10.1371/journal.pone.0021400 21731731 PMC3120881 · DOI
  40. [41]Nehrt NL Clark WT Radivojac P Hahn MW Testing the ortholog conjecture with comparative functional genomic data from mammals PLoS Comput Biol 2011 7 e1002073 10.1371/journal.pcbi.1002073 21695233 PMC3111532 · DOI
  41. [42]Das S Yu L Gaitatzes C Rogers R Freeman J Bienkowska J Biology’s new Rosetta stone Nature 1997 385 29 30 10.1038/385029a0 8985242 · DOI
  42. [43]Fickett JW ORFs and genes: how strong a connection? J Comput Biol 1995 2 117 123 10.1089/cmb.1995.2.117 7497114 · DOI
  43. [44]Denton JF Lugo-Martinez J Tucker AE Schrider DR Warren WC Hahn MW Extensive error in the number of genes inferred from draft genome assemblies PLoS Comput Biol 2014 10 e1003998 10.1371/journal.pcbi.1003998 25474019 PMC4256071 · DOI
  44. [45]Prabh N Rödelsperger C Are orphan genes protein-coding, prediction artifacts, or non-coding RNAs? BMC Bioinformatics 2016 17 226 10.1186/s12859-016-1102-x 27245157 PMC4888513 · DOI
  45. [46]Nevers Y Defosset A Lecompte O Pontarotti P Orthology: promises and challenges Evolutionary Biology—A Transdisciplinary Approach 2020 Cham Springer International Publishing 203 228
  46. [47]Henry J Favrel P Boucaud-Camou E Isolation and identification of a novel Ala-Pro-Gly-Trp-amide-related peptide inhibiting the motility of the mature oviduct in the cuttlefish Sepia Officinalis Peptides 1997 18 1469 1474 10.1016/S0196-9781(97)00241-6 9437704 · DOI
  47. [48]Labeit S Kolmerer B Titins: giant proteins in charge of muscle ultrastructure and elasticity Science 1995 270 293 296 10.1126/science.270.5234.293 7569978 · DOI
  48. [49]White SH The evolution of proteins from random amino acid sequences: II. Evidence from the statistical distributions of the lengths of modern protein sequences J Mol Evol 1994 38 383 94 10.1007/BF00163155 8007006 · DOI
  49. [50]Lopes I Altab G Raina P de Magalhães JP Gene Size Matters: An Analysis of Gene Length in the Human Genome Front Genet 2021 12 559998 10.3389/fgene.2021.559998 33643374 PMC7905317 · DOI
  50. [51]Urrutia AO Hurst LD The signature of selection mediated by expression on human genes Genome Res 2003 13 2260 2264 10.1101/gr.641103 12975314 PMC403694 · DOI
  51. [52]Castillo-Davis CI Mekhedov SL Hartl DL Koonin EV Kondrashov FA Selection for short introns in highly expressed genes Nat Genet 2002 31 415 418 10.1038/ng940 12134150 · DOI
  52. [53]Debès C Wang M Caetano-Anollés G Gräter F Evolutionary optimization of protein folding PLoS Comput Biol 2013 9 e1002861 10.1371/journal.pcbi.1002861 23341762 PMC3547816 · DOI
  53. [54]Wang M Caetano-Anollés G The evolutionary mechanics of domain organization in proteomes and the rise of modularity in the protein world Structure 2009 17 66 78 10.1016/j.str.2008.11.008 19141283 · DOI
  54. [55]Wang M Kurland CG Caetano-Anollés G Reductive evolution of proteomes and protein structures Proc Natl Acad Sci U S A 2011 108 11954 11958 10.1073/pnas.1017361108 21730144 PMC3141956 · DOI
  55. [56]Doolittle RF. The multiplicity of domains in proteins. Annual Reviews 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303–0139, USA; 2003. Available from: https://www.annualreviews.org/doi/abs/10.1146/annurev.bi.64.070195.001443. Cited 6 Aug 2021. · DOI
  56. [58]Shahzad K Mittenthal JE Caetano-Anollés G The organization of domains in proteins obeys Menzerath-Altmann’s law of language BMC Syst Biol 2015 9 44 10.1186/s12918-015-0192-9 26260760 PMC4531524 · DOI
  57. [59]Lam SD Dawson NL Das S Sillitoe I Ashford P Lee D Gene3D: expanding the utility of domain assignments Nucleic Acids Res 2016 44 D404 D409 10.1093/nar/gkv1231 26578585 PMC4702871 · DOI
  58. [60]Altenhoff AM Glover NM Train C-M Kaleb K Warwick Vesztrocy A Dylus D The OMA orthology database in 2018: retrieving evolutionary relationships among all domains of life through richer web and programmatic interfaces Nucleic Acids Res 2018 46 D477 D485 10.1093/nar/gkx1019 29106550 PMC5753216 · DOI · Paper page
  59. [61]Cock PJA Antao T Chang JT Chapman BA Cox CJ Dalke A Biopython: freely available Python tools for computational molecular biology and bioinformatics Bioinformatics Oxford Academic 2009 25 1422 1423 10.1093/bioinformatics/btp163 PMC2682512 19304878 · DOI · Paper page
  60. [62]Sukumaran J Holder MT DendroPy: a Python library for phylogenetic computing Bioinformatics 2010 26 1569 1571 10.1093/bioinformatics/btq228 20421198 · DOI
  61. [63]Virtanen P Gommers R Oliphant TE Haberland M Reddy T Cournapeau D SciPy 1.0: fundamental algorithms for scientific computing in Python Nat Methods 2020 17 261 72 10.1038/s41592-019-0686-2 32015543 PMC7056644 · DOI · Paper page
  62. [65]Harris CR Millman KJ van der Walt SJ Gommers R Virtanen P Cournapeau D Array programming with NumPy Nature 2020 585 357 362 10.1038/s41586-020-2649-2 32939066 PMC7759461 · DOI · Paper page
  63. [67]Hunter JD Matplotlib: A 2D Graphics Environment Comput Sci Eng 2007 9 90 95 10.1109/MCSE.2007.55 · DOI · Paper page
  64. [68]Altenhoff AM Škunca N Glover N Train C-M Sueki A Piližota I The OMA orthology database in 2015: function predictions, better plant support, synteny view and other improvements Nucleic Acids Res 2015 43 D240 D249 10.1093/nar/gku1158 25399418 PMC4383958 · DOI
  65. [69]Klopfenstein DV Zhang L Pedersen BS Ramírez F Warwick Vesztrocy A Naldi A GOATOOLS: A Python library for Gene Ontology analyses Sci Rep 2018 8 10872 10.1038/s41598-018-28948-z 30022098 PMC6052049 · DOI
  66. [70]Reijnders MJMF Waterhouse RM Summary Visualizations of Gene Ontology Terms With GO-Figure! Front Bioinform 2021 1 6 10.3389/fbinf.2021.638255 PMC9581009 36303779 · DOI
  67. [73]Gene Ontology Consortium The Gene Ontology resource: enriching a GOld mine Nucleic Acids Res 2021 49 D325 D334 10.1093/nar/gkaa1113 33290552 PMC7779012 · DOI · Paper page
  68. [74]Ashburner M Ball CA Blake JA Botstein D Butler H Cherry JM Gene ontology: tool for the unification of biology The Gene Ontology Consortium Nat Genet 2000 25 25 29 10.1038/75556 10802651 PMC3037419 · DOI · Paper page
  69. [75]Brumlik MJ Wei S Finstad K Nesbit J Hyman LE Lacey M Identification of a novel mitogen-activated protein kinase in Toxoplasma gondii Int J Parasitol 2004 34 1245 1254 10.1016/j.ijpara.2004.07.007 15491587 · DOI
  70. [76]Wei S Marches F Daniel B Sonda S Heidenreich K Curiel T Pyridinylimidazole p38 mitogen-activated protein kinase inhibitors block intracellular Toxoplasma gondii replication Int J Parasitol 2002 32 969 977 10.1016/S0020-7519(02)00061-9 12076626 · DOI
  71. [77]Wei F Wang W Liu Q Protein kinases of Toxoplasma gondii: functions and drug targets Parasitol Res 2013 112 2121 2129 10.1007/s00436-013-3451-y 23681193 · DOI
  72. [78]Sibley LD Intracellular parasite invasion strategies Science 2004 304 248 253 10.1126/science.1094717 15073368 · DOI
  73. [79]Suarez C Lentini G Ramaswamy R Maynadier M Aquilini E Berry-Sterkers L A lipid-binding protein mediates rhoptry discharge and invasion in Plasmodium falciparum and Toxoplasma gondii parasites Nat Commun 2019 10 4041 10.1038/s41467-019-11979-z 31492901 PMC6731292 · DOI
  74. [81]Altschul SF Gish W Miller W Myers EW Lipman DJ Basic local alignment search tool J Mol Biol 1990 215 403 410 10.1016/S0022-2836(05)80360-2 2231712 · DOI · Paper page
  75. [82]Camacho C Coulouris G Avagyan V Ma N Papadopoulos J Bealer K BLAST+: architecture and applications BMC Bioinformatics 2009 10 421 10.1186/1471-2105-10-421 20003500 PMC2803857 · DOI · Paper page

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Authors
Nevers, Y., Glover, N. M., Dessimoz, C., & Lecompte, O.
Affiliations
  • SIB Swiss Institute of Bioinformatics (CH)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
Nevers, Yannis
ORCID
Venue
Genome Biology
Publisher
Springer Science and Business Media LLC
Published
2023-06-08
Volume
24
Issue
1
Pages
135-135
ISSN
  • 1465-6906 (ISSN-L)
  • 1474-760X
DOI
10.1186/s13059-023-02973-2
PMC
PMC10251718
OpenAlex
W4379966447
Cited by
51
References
4
Citations by year
2026: 12 · 2025: 19 · 2024: 15 · 2023: 3 · 2022: 2
FWCI
4.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • SERVAL (Université de Lausanne) (submittedVersion, cc-by)
  • HAL (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • IRIS (submittedVersion, cc-by)
Funders
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (183723, 205085)
  • University of Lausanne
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fractal and DNA sequence analysis
Keywords
protein length distribution, protein length, bacteria, archaea, eukaryotes, comparative genomics, protein domains
MeSH terms
Amino Acid Sequence, Archaea, Bacteria, Proteins, Sequence Analysis, Protein, Proteome, Eukaryota, Molecular Sequence Annotation

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