Orthologues, Paralogues and Horizontal Gene Transfer in the Human Holobiont

Shannon Soucy, University of Connecticut, Storrs, Connecticut, USA
Lorraine Olendzenski, St. Lawrence University, Canton, New York, USA
J Peter Gogarten, University of Connecticut, Storrs, Connecticut, USA

Published online: March 2013

DOI: 10.1002/9780470015902.a0005298.pub3

Evolution is commonly measured using comparative phylogenetic analysis. Comparisons of orthologous characters and sequences from different species are used to infer organismal evolution. Analyses of duplicated genes can be used to root phylogenetic trees and infer ancestral groups. The expansion of gene families through gene and genome duplications allowed more complex regulatory and developmental pathways to evolve in multicellular eukaryotes. In prokaryotes and single-celled eukaryotes, the acquisition of foreign genes by horizontal gene transfer is the main mechanism for gene family expansion; it allows genomes to evolve new traits quickly and facilitates the assembly of new metabolic pathways. Additionally, prokaryotic organisms with short generation times will accumulate genetic adaptations at a much faster rate than organisms with longer generation times (e.g. humans). In multicellular animals where somatic cells and gametes are separate, acquisition of foreign genes is rare, leading to high levels of similarity in gene content. However, multicellular eukaryotes have evolved in close association with prokaryotic symbionts that impact development, physiology and ecology of the association. To understand the evolution of the complex human systems, we must consider the genomes of the associated microbiota, known as the microbiome. We must therefore consider the human as a holobiont, a complex ecosystem, whose evolutionary fitness is determined by the host, the symbionts and their interactions.

Key Concepts:

  • Orthologous structures or sequences in two organisms are homologues that evolved from the same feature in their last common ancestor; orthologues reflect organismal evolution.
  • Paralogues are homologues whose evolution reflects gene duplication events.
  • Genomes can evolve by acquiring genes through horizontal gene transfer or from the fusion of complete genomes through symbiosis.
  • Individual humans can differ slightly in genome content with variation related primarily to deletions or regions of segmental duplication.
  • Apparent differences in complexity between species may be due to a varying amount of noncoding regulatory sequence, regulating a fairly stable core of protein-coding genes.
  • Repeated sequences derived from transposable elements comprise a large portion of the genome and can have a significant role in gene duplication through the formation of pseudogenes that lack introns.
  • Duplicated segments in the human genome are generally enriched in protein coding genes and have the potential to evolve novel transcripts, either as whole-gene duplications or through the creation of mosaic genes.
  • Variations in the number of paralogues in humans reveal genomic regions under selective pressures.
  • Orthologous regions amongst genomes are found in both protein coding exons and noncoding regions of the genome. Rapidly evolving regions of the human genome include intergenic regions that may be important for gene regulation.
  • Humans can be viewed as a holobiont, a complex ecosystem whose evolutionary fitness is determined by interactions of the host and microbiota.
  • The microbiome, the sum of microbial genomes carried in our symbionts, encode metabolic capacities that we have not had to evolve in our nuclear genome.

Keywords: orthologous; paralogous; symbiosis; holobiont; hologenome; coevolution; gene duplication; horizontal gene transfer

Figure 1. To the left of the body, underlined in red, are the number of human cells which make up the average human body, to the right underlined in purple are the number of prokaryotic cells associated with different locations of the body. The units are bacterial cells per ml, and thus the cumulative amount of prokaryotic cells in each organ is much greater. Additionally, beneath the body is a chart comparing the number of human cells and genes in the human genome (in red) to the number of cells per ml of bacteria in the large intestine, one of the most heavily colonised areas of the human body, and the number of nonredundant prokaryotic genes isolated from the large intestine (in purple).
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 References
    Andersson JO, Doolittle WF and Nesbo CL (2001) Genomics. Are there bugs in our genome? Science 292: 1848–1850.
    Bailey JA, Yavor AM, Viggiano L et al. (2002) Human-specific duplication and mosaic transcripts: the recent paralogous structure of chromosome 22. American Journal of Human Genetics 70: 83–100.
    Bejerano G, Pheasant M, Makunin I et al. (2004) Ultraconserved elements in the human genome. Science 304: 1321–1325.
    Ciccarelli FD, von Mering C, Suyama M et al. (2005) Complex genomic rearrangements lead to novel primate gene function. Genome Research 15: 343–351.
    Clemente JC, Ursell LK, Parfrey LW and Knight R (2012) The impact of the gut microbiota on human health: an integrative view. Cell 148: 1258–1270.
    Fitch WM (1970) Distinguishing homologous from analogous proteins. Systematic Zoology 19: 99–113.
    Fraune S and Bosch TCG (2010) Why bacteria matter in animal development and evolution. Bioessays 32: 571–580.
    Gill SR, Pop M, DeBoy RT et al. (2006) Metagenomic analysis of the human distal gut microbiome. Science 312: 1355–1359.
    Gogarten JP (1994) Which is the most conserved group of proteins? Homology–orthology, paralogy, xenology, and the fusion of independent lineages. Journal of Molecular Evolution 39: 541–543.
    Gokcumen O, Babb PL, Iskow RC et al. (2011) Refinement of primate copy number variation hotspots identifies candidate genomic regions evolving under positive selection. Genome Biology 12(5): R52.
    Gough E, Shaikh H and Manges AR (2011) Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clinical Infectious Diseases 53(10): 994–1002.
    Han K, Lou DI and Sawyer SL (2011) Identification of a genomic reservoir for new TRIM genes in primate genomes. PLoS Genetics 7(12): e1002388.
    Hehemann JH, Correc G, Barbeyron T et al. (2010) Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota. Nature 464: 908–912.
    Johnson JM, Edwards S, Shoemaker D and Schaadt AA (2005) Dark matter in the genome: evidence of widespread transcription detected by microarray tiling experiments. Trends in Genetics 21: 93–102.
    Johnson ME, Viggiano L, Bailey JA et al. (2001) Positive selection of a gene family during the emergence of humans and African apes. Nature 413: 514–519.
    Jun J, Ryvkin P, Hemphill E, Mandoiu I and Nelson C (2009) The birth of new genes by RNA- and DNA-mediated duplication during mammalian evolution. Journal of Computational Biology 16: 1429–1444.
    Katzman S, Kern AD, Bejerano G et al. (2007) Human genome ultraconserved elements are ultraselected. Science 317: 915.
    Kazazian HH Jr (2004) Mobile elements: drivers of genome evolution. Science 303: 1626–1632.
    Kondo N, Nikoh N, Ijichi N, Shimada M and Fukatsu T (2002) Genome fragment of Wolbachia endosymbiont transferred to X chromosome of host insect. Proceedings of the National Academy of Sciences of the USA 99: 14280–14285.
    Lander ES, Linton LM, Birren B et al. (2001) Initial sequencing and analysis of the human genome. Nature 409: 860–921.
    Lee YK and Mazmanian SK (2010) Has the microbiota played a critical role in the evolution of the adaptive immune system? Science 330: 1768–1773.
    Lester CH, Frimodt-Moller N, Sorenson TL, Monnet DL and Hammerum AM (2006) In vivo transfer of the vanA resistance gene from an Enterococcus faecium isolate of animal origin to an E. faecium isolate of human origin in the intestines of human volunteers. Antimicrobial Agents and Chemotherapy 50: 596–599.
    Li WH, Gu Z, Wang H and Nekrutenko A (2001) Evolutionary analyses of the human genome. Nature 409: 847–849.
    Liu L, Chen X, Skogerbø G et al. (2012) The human microbiome: a hot spot of microbial horizontal gene transfer. Genomics 100: 265–270.
    Lukjancenko O, Wassenaar TM and Ussery DW (2010) Comparison of 61 sequenced Escherichia coli genomes. Microbial Ecology 60: 708–720.
    Mattar AF, Drongowski RA, Coran AG and Harmon CM (2001) Effect of probiotics on enterocyte bacterial translocation in vitro. Pediatric Surgery International 17: 265–268.
    Meader S, Ponting CP and Lunter G (2010) Massive turnover of functional sequence in human and other mammalian genomes. Genome Research 20: 1335–1343.
    Mills RE, Bennett EA, Iskow RC and Devine SE (2007) Which transposable elements are active in the human genome? Trends in Genetics 23: 183–191.
    Ochman H, Worobey M, Kuo CH et al. (2010) Evolutionary relationships of wild hominids recapitulated by gut microbial communities. PLoS Biology 8(11): e1000546.
    Parfrey LW and Knight R (2012) Spatial and temporal variability of the human microbiota. Clinical Microbiology and Infection 18: 5–7.
    Pertea M and Salzberg SL (2010) Between a chicken and a grape: estimating the number of human genes. Genome Biology 11: 206.
    Pertea M (2012) The human transcriptome: an unfinished story. Genes (Basel) 3(3): 344–360.
    Pollard KS, Salama SR, King B et al. (2006) Forces shaping the fastest evolving regions in the human genome. PLoS Genetics 2: e168.
    Ponjavic J, Ponting CP and Lunter G (2007) Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs. Genome Research 17: 556–565.
    Ponting CP and Hardison R (2011) What fraction of the human genome is functional? Genome Research 21: 1769–1776.
    Prosdocimi F, Linard B, Pontarotti P, Poch O and Thompson JD (2012) Controversies in modern evolutionary biology: the imperative for error detection and quality control. BMC Genomics 13: 5.
    Qin J, Li R and Raes J (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464: 59–65.
    Rook GAW (2012) A Darwinian view of the hygiene or “old friends” hypothesis. Microbe 7(4): 173–180.
    Rosenberg E, Sharon G and Zilber-Rosenberg I (2009) The hologenome theory of evolution contains Lamarckian aspects within a Darwinian framework. Environmental Microbiology 12: 2959–2962.
    Salzberg SL, White O, Peterson J et al. (2001) Microbial genes in the human genome: lateral transfer or gene loss? Science 292: 1903–1906.
    Shaye DD and Greenwald I (2011) OrthoList: a compendium of C. elegans genes with human orthologs. PLoS One 6: e20085.
    Siepel A, Bejerano G, Pedersen JS et al. (2005) Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Research 15: 1034–1050.
    Smillie CS, Smith MB and Friedman J (2011) Ecology drives a global network of gene exchange connecting the human microbiome. Nature 480: 241–244.
    Spor A, Koren O and Ley R (2011) Unravelling the effects of the environment and host genotype on the gut microbiome. Nature Reviews 9: 279–290.
    The Chimpanzee Sequencing and Analysis Consortium (2005) Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437: 69–87.
    Toft C and Andersson SEG (2010) Evolutionary microbial genomics insights into bacterial host adaptation. Nature Reviews 11: 465–475.
    Turnbaugh PJ, Ley RE, Mahowald MA et al. (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444(7122): 1027–1031.
    Van De Peer Y, Maere S and Meyer A (2009) The evolutionary significance of ancient genome duplications. Nature Reviews Genetics 10(10): 725–732.
    Walter J and Ley R (2011) The human gut microbiome: ecology and recent evolutionary changes. Annual Review of Microbiology 65: 411–429.
    Zhang L, Lu HHS, Chung WY, Yang J and Li WH (2005) Patterns of segmental duplication in the human genome. Molecular Biology and Evolution 22: 135–141.
    Zhang ZD, Paccanaro A, Fu Y et al. (2007) Statistical analysis of the genomic distribution and correlation of regulatory elements in the ENCODE regions. Genome Research 17: 787–797.
 Further Reading
    Chow J, Lee SM, Shen Y, Khosravi A and Mazmanian SK (2010) Host-bacterial symbiosis in health and disease. Advances in Immunology 107: 243–274.
    ENCODE Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57–74.
    Human Microbiome Project (2012) Structure, function and diversity of the healthy human microbiome. Nature 486: 207–214.
    Lynch M and Conery JS (2000) The evolutionary fate and consequences of duplicate genes. Science 290(5494): 1151–1155.
    Subramanian G, Adams MD, Venter JC and Broder S (2001) Implications of the human genome for understanding human biology and medicine. Journal of the American Medical Association 286: 2296–2307.
    Thomas F, Barbeyron T, Tonon T et al. (2012) Characterization of the first alginolytic operons in a marine bacterium: from their emergence in marine flavobacteria to their independent transfers to marine proteobacteria and human gut bacteriodetes. Environmental Microbiology 14(9): 2379–2394.
    Wolff MJ, Broadhurst MJ and Loke P (2012) Helminthic therapy: improving mucosal barrier function. Trends in Parasitology 28(5): 187–194.

Related Sub-Topics:

Coevolution | Molecular Evolution | Evolution: Theories and Ideas | Evolutionary Processes | Human Evolution | Bacteria | Genomes and Chromosomes | Microbial Evolution and Taxonomy
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Article Title: Orthologues, Paralogues and Horizontal Gene Transfer in the Human Holobiont
 
How to Cite close
Soucy, Shannon, Olendzenski, Lorraine, and Gogarten, J Peter(Mar 2013) Orthologues, Paralogues and Horizontal Gene Transfer in the Human Holobiont. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005298.pub3]