The its Region of Nuclear Ribosomal DNA: A Valuable Source of Evidence on Angiosperm Phylogeny

The internal transcribed spacer (ITS) region of 18S-26S nuclear ribosomal DNA (nrDNA) has proven to be a useful source of characters for phylogenetic studies in many angiosperm families. The two spacers of this region, ITS-1 and ITS-2 (each <300 bp), can be readily amplified by PCR and sequenced using universal primers, even from DNAs of herbarium specimens. Despite high copy numbers of both spacers, the near uniformity ofITS paralogues, attributed to rapid concerted evolution, allows direct sequencing of pooled PCR products in many species. Divergent paralogues, where detected, require cloning, but may offer a means of obtaining multiple estimates of organismal relationships and of determining placement of the root in a phylogeny independent of outgroup considerations. In reported studies, variation between ITS sequences is mostly attributable to point mutations. A relatively minor proportion of sites is affected by insertions or deletions (indels) among sequences that are similar enough to have retained sufficient signal for phylogenetic analysis. Within these limits, sequence alignment is generally unambiguous except in small regions of apparently lower structural constraint. Phylogenetic analyses of combined, data sets from both spacers, where examined, yield trees with greater resolution and internal support than analyses based on either spacer alone. This beneficial effect of simultaneous analysis is not surprising based on the low number of useful characters in each spacer. This effect also suggests high complementarity of spacer data, in accord with similarity in size, sequence variability, and G + C content of ITS-1 and ITS-2 in most investigated groups of closely related angiosperms. Nonindependent evolution of ITS sites involved in intraspacer RNA base-pairing may occur, given possible functional constraints, but preliminary secondary structure analyses of ITS-2 in Calycadenia (Asteraceae) show no definite evidence of compensatory spacer mutations. As expected, levels of ITS sequence variation suitable for phylogenetic analysis are found at various taxonomic levels within families, depending on the lineage. The apparent rates of ITS molecular evolution are roughly correlated with plant life-form, as with chloroplast DNA (cpDNA) data, but reasons for this observation are unclear. ITS characters have improved our understanding of angiosperm phylogeny in several groups by (1) corroborating earlier unexpected findings, (2) resolving conflicts between other data sets, (3) improving resolution of species relationships, or (4) providing direct evidence of reticulate volution. Hybridization or sorting of ancestral polymorphism ina lineage can complicate interpretation ftrees based on any type of evolutionary evidence, including ITS or cpDNA sequences, particularly in the absence of at least one independent phylogenetic data set from the same organisms. The need for phylogenetic markers from the nuclear genome, to complement he rapidly growing body of cpDNA data, makes the ITS region a particularly valuable resource for plant systematists. Until recently, most plant systematists reserved DNA sequencing for phylogenetic analyses of taxa with sequences too divergent to be easily interpreted by restriction site mapping. Consequently, only moderately to slowly evolving DNA sequences have been used widely in plant phylogenetics (e.g., rbcL, see Chase et al., 1993; 18S and 26S nuclear ribosomal DNA, see Bult et al., 1995; Nickrent & Soltis, 1995). With the recent advent of polymerase chain reaction (PCR) technology, however, DNA 1 Support was provided in part by the NSF (BSR-9002260 to BGB, BSR-9106226 to CSC, and BSR-8822658 to MJD); Duke University (to BGB); University of Nevada, Reno (to MJS); and University of Arizona (to MJD). We thank Pam Soltis, Jonathan Wendel, and an anonymous reviewer for helpful comments on the manuscript. BGB also thanks Doug and Pam Soltis for inviting him to participate in the symposium at which some of this material was presented. 2 Department of Botany, Box 90338, Duke University, Durham, North Carolina 27708-0338, U.S.A. Author for correspondence. 3New address: Jepson Herbarium and Department of Integrative Biology, University of California, 1001 Valley Life Sciences Building # 2465, Berkeley, California 94720-2465, U.S.A. 4Department of Biology, University of Nevada, Reno, Nevada 89557, U.S.A. 5Rancho Santa Ana Botanic Garden, 1500 North College Avenue, Claremont, California 91711, U.S.A. 6 Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, Arizona 85721, U.S.A. 7Department of Plant Biology and Pathology, University of Maine, Orono, Maine 04469, U.S.A. 8 Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, U.S.A. ANN. MISSOURI BOT. GARD. 82: 247-277. 1995. 248 Annals of the Missouri Botanical Garden

[1]  D. Schlessinger,et al.  Mouse rDNA: sequences and evolutionary analysis of spacer and mature RNA regions. , 1983, Molecular and cellular biology.

[2]  A. Kato,et al.  Nucleotide sequences of the 5.8S rRNA gene and internal transcribed spacer regions in carrot and broad bean ribosomal DNA , 1989, Journal of Molecular Evolution.

[3]  R. D'Ovidio Nucleotide sequence of a 5.8S rDNA gene and of the internal transcribed spacers from Populus deltoides , 1992, Plant Molecular Biology.

[4]  J. Huelsenbeck,et al.  SUCCESS OF PHYLOGENETIC METHODS IN THE FOUR-TAXON CASE , 1993 .

[5]  D. Skinner,et al.  Phylogenetic analysis of Sorghum and related taxa using internal transcribed spacers of nuclear ribosomal DNA , 1994, Theoretical and Applied Genetics.

[6]  M. Nei,et al.  Relationships between gene trees and species trees. , 1988, Molecular biology and evolution.

[7]  A. Deisseroth,et al.  Improved PCR sequencing with formamide. , 1992, Trends in genetics : TIG.

[8]  Y. Kan,et al.  Rapid duplication and loss of genes coding for the alpha chains of hemoglobin. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[9]  W. Fitch Distinguishing homologous from analogous proteins. , 1970, Systematic zoology.

[10]  D. Hillis,et al.  Ribosomal RNA secondary structure: compensatory mutations and implications for phylogenetic analysis. , 1993, Molecular biology and evolution.

[11]  R. Planta,et al.  Functional analysis of internal transcribed spacer 2 of Saccharomyces cerevisiae ribosomal DNA. , 1992, Journal of molecular biology.

[12]  D. Soltis,et al.  Phylogenetic Relationships among the Genera of Taxodiaceae and Cupressaceae: Evidence from rbcL Sequences , 1994 .

[13]  G. Learn,et al.  Ribosomal DNA Variation within and among Plant Populations , 1988 .

[14]  A. Queiroz For Consensus (Sometimes) , 1993 .

[15]  J. Wendel,et al.  An unusual ribosomal DNA sequence from Gossypium gossypioides reveals ancient, cryptic, intergenomic introgression. , 1995, Molecular phylogenetics and evolution.

[16]  I. Capesius,et al.  Nucleotide sequence of the 18S-25S spacer region from mustard DNA. , 1989, Nucleic acids research.

[17]  D. Nickrent,et al.  A MOLECULAR PHYLOGENY OF ARCEUTHOBIUM (VISCACEAE) BASED ON NUCLEAR RIBOSOMAL DNA INTERNAL TRANSCRIBED SPACER SEQUENCES , 1994 .

[18]  C. Sterling COMPARATIVE MORPHOLOGY OF THE CARPEL IN THE ROSACEAE. I. PRUNOIDEAE: PRUNUS , 1964 .

[19]  K. H. Asay,et al.  Phylogenetic relationships of 10 grass species: an assessment of phylogenetic utility of the internal transcribed spacer region in nuclear ribosomal DNA in monocots. , 1994, Genome.

[20]  M. Sanderson,et al.  RECONSTRUCTION OF ORGANISMAL AND GENE PHYLOGENIES FROM DATA ON MULTIGENE FAMILIES: CONCERTED EVOLUTION, HOMOPLASY, AND CONFIDENCE , 1992 .

[21]  L. Savard,et al.  Genetic diversity and phylogenetic relationships between birches and alders using ITS, 18S rRNA and rbcL gene sequences. , 1993, Molecular phylogenetics and evolution.

[22]  D. Hillis,et al.  Evidence for biased gene conversion in concerted evolution of ribosomal DNA. , 1991, Science.

[23]  E. Zimmer,et al.  Molecular evolution and phylogenetic implications of internal transcribed spacer sequences of Ribosomal DNA in Winteraceae , 1993 .

[24]  J. Bachellerie,et al.  The complete nucleotide sequence of mouse 28S rRNA gene. Implications for the process of size increase of the large subunit rRNA in higher eukaryotes. , 1984, Nucleic acids research.

[25]  J. Lee,et al.  Yeast precursor ribosomal RNA. Molecular cloning and probing the higher-order structure of the internal transcribed spacer I by kethoxal and dimethylsulfate modification. , 1990, Journal of molecular biology.

[26]  T. White Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics , 1990 .

[27]  R. Vilgalys,et al.  Phylogenetic analyses of Polemoniaceae using nucleotide sequences of the plastid gene matK , 1994 .

[28]  C. Sterling COMPARATIVE MORPHOLOGY OF THE CARPEL IN THE ROSACEAE. VIII. SPIRAEOIDEAE: HOLODISCEAE, NEILLIEAE, SPIRAEEAE, ULMARIEAE , 1966 .

[29]  M. Donoghue,et al.  The Suitability of Molecular and Morphological Evidence in Reconstructing Plant Phylogeny , 1992 .

[30]  R. Jansen,et al.  Restriction fragment analysis of chloroplast DNA and the systematics of Viguiera and related genera (Asteraceae: Heliantheae) , 1989 .

[31]  Phylogenetic origin of the Monotropoideae inferred from partial 28S ribosomal RNA gene sequences , 1992 .

[32]  D. Soltis,et al.  Systematic and evolutionary implications of rbcL sequence variation in Rosaceae , 1994 .

[33]  C. Ritland,et al.  Variation in the ribosomal internal transcribed spacers (ITS1 and ITS2) among eight taxa of the Mimulus guttatus species complex. , 1993, Molecular biology and evolution.

[34]  G. D. Carr,et al.  ADAPTIVE RADIATION IN THE HAWAIIAN SILVERSWORD ALLIANCE (COMPOSITAE‐MADIINAE). II. CYTOGENETICS OF ARTIFICIAL AND NATURAL HYBRIDS , 1986, Evolution; international journal of organic evolution.

[35]  Sherif Abou Elela,et al.  Intragenic processing in yeast rRNA is dependent on the 3' external transcribed spacer. , 1994, Journal of molecular biology.

[36]  J. Doyle,et al.  Gene Trees and Species Trees: Molecular Systematics as One-Character Taxonomy , 1992 .

[37]  R. Planta,et al.  Functional analysis of transcribed spacers of yeast ribosomal DNA. , 1990, The EMBO journal.

[38]  J. W. Taylor,et al.  Phylogeny of five fungus-like protoctistan Phytophthora species, inferred from the internal transcribed spacers of ribosomal DNA. , 1992, Molecular biology and evolution.

[39]  I. Unfried,et al.  Nucleotide sequence of the 5.8S and 25S rRNA genes and of the internal transcribed spacers from Arabidopsis thaliana , 1990, Nucleic Acids Res..

[40]  R. Nazar,et al.  A conserved core structure in the 18–25S rRNA intergenic region from tobacco, Nicotiana rustica , 1991, Plant Molecular Biology.

[41]  C. Cullis Mutation, developmental selection and plant evolution , 1990 .

[42]  S. Rogers,et al.  Ribosomal RNA genes in plants: variability in copy number and in the intergenic spacer , 1987, Plant Molecular Biology.

[43]  V. Hemleben,et al.  Nucleotide sequence of the 18S-25S spacer region from rDNA of mung bean. , 1989, Nucleic acids research.

[44]  Wayne P. Maddison,et al.  Macclade: Analysis of Phylogeny and Character Evolution/Version 3 , 1992 .

[45]  B S Weir,et al.  Testing for equality of evolutionary rates. , 1992, Genetics.

[46]  R. Schmickel,et al.  Sequence and structure correlation of human ribosomal transcribed spacers. , 1990, Journal of molecular biology.

[47]  S. Muse,et al.  Relative rates of nucleotide substitution in the chloroplast genome. , 1993, Molecular phylogenetics and evolution.

[48]  Masahiro Sugiura,et al.  Nucleotide sequence of the 17S–25S spacer region from rice rDNA , 1985, Plant Molecular Biology.

[49]  C. Bult,et al.  Cryptic Sequence Simplicity, Nucleotide Composition Bias, and Molecular Coevolution in the Large Subunit of Ribosomal DNA in Plants: Implications for Phylogenetic Analyses , 1995 .

[50]  Michael J. Sanderson,et al.  MONOPHYLY OF ANEUPLOID ASTRAGALUS (FABACEAE): EVIDENCE FROM NUCLEAR RIBOSOMAL DNA INTERNAL TRANSCRIBED SPACER SEQUENCES , 1993 .

[51]  M. Donoghue A Preliminary Analysis of Phylogenetic Relationships in Viburnum (Caprifoliaceae s.l.) , 1983 .

[52]  J. Porter Phylogeny of Polemoniaceae Based on Nuclear Ribosomal Internal Transcribed Spacer DNA Sequences , 1996 .

[53]  Douglas E. Soltis,et al.  Molecular Systematics of Plants , 1992, Springer US.

[54]  T. Kavanagh,et al.  Structure of melon rDNA and nucleotide sequence of the 17–25S spacer region , 1988, Theoretical and Applied Genetics.

[55]  L. Rieseberg,et al.  Molecular Evidence and Plant Introgression , 1992 .

[56]  James F. Smith Phylogenetics of seed plants : An analysis of nucleotide sequences from the plastid gene rbcL , 1993 .

[57]  P. Winship,et al.  An improved method for directly sequencing PCR amplified material using dimethyl sulphoxide. , 1989, Nucleic acids research.

[58]  E. Zimmer,et al.  Ribosomal RNA as a Phylogenetic Tool in Plant Systematics , 1992 .

[59]  Douglas E. Soltis,et al.  Phylogenetic Inference in Saxifragaceae Sensu Stricto and Gilia (Polemoniaceae) Using matK Sequences , 1995 .

[60]  B. Weir,et al.  Detecting substitution-rate heterogeneity among regions of a nucleotide sequence. , 1994, Molecular biology and evolution.

[61]  L. Hall,et al.  Multiple heterogeneities in the transcribed spacers of ribosomal DNA from Xenopus laevis. , 1983, Nucleic acids research.

[62]  H A Erlich,et al.  Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[63]  T. Sang,et al.  Radiation of the endemic genus Dendroseris (Asteraceae) on the Juan Fernandez Islands: evidence from sequences of the its regions of nuclear ribosomal DNA , 1994 .

[64]  J. Bull,et al.  Partitioning and combining data in phylogenetic analysis , 1993 .

[65]  R. Planta,et al.  Separate structural elements within internal transcribed spacer 1 of Saccharomyces cerevisiae precursor ribosomal RNA direct the formation of 17S and 26S rRNA. , 1994, Nucleic acids research.

[66]  J. W. Pendleton,et al.  Surveys of Gene Families Using Polymerase Chain Reaction: PCR Selection and PCR Drift , 1994 .

[67]  Michael T. Clegg,et al.  Relative rates of nucleotide substitution at the rbcl locus of monocotyledonous plants , 1992, Journal of Molecular Evolution.

[68]  T. Mabry,et al.  Phylogenetic and evolutionary implications of nuclear ribosomal DNA variation in dwarf dandelions (Krigia, Lactuceae, Asteraceae) , 1991, Plant Systematics and Evolution.

[69]  S. Abel,et al.  Nucleotide sequence of the 17S-25S spacer region from tomato rDNA. , 1988, Nucleic acids research.

[70]  E. Zimmer,et al.  Nucleotide sequences of the internal transcribed spacers and 5.8S rRNA gene in Canella winterana (Magnoliales; Canellaceae). , 1992, Nucleic acids research.

[71]  M. Ganal,et al.  GC balance in the internal transcribed spacers ITS 1 and ITS 2 of nuclear ribosomal RNA genes , 1990, Journal of Molecular Evolution.

[72]  J. Woolliams,et al.  What is Genetic Diversity , 2007 .

[73]  W. Wheeler,et al.  Paired sequence difference in ribosomal RNAs: evolutionary and phylogenetic implications. , 1988, Molecular biology and evolution.

[74]  K. Mullis,et al.  Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. , 1988, Science.

[75]  Ming-Yang Kao,et al.  Phylogeny Reconstruction , 2008, Encyclopedia of Algorithms.

[76]  S. Osawa,et al.  Evolutionary relationship of archaebacteria, eubacteria, and eukaryotes inferred from phylogenetic trees of duplicated genes. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[77]  R. Jorgensen,et al.  Modes and Tempos in the Evolution of Nuclear Ribosomal DNA: New Characters for Evolutionary Studies and New Markers for Genetic and Population Studies , 1988 .

[78]  A. Kluge A Concern for Evidence and a Phylogenetic Hypothesis of Relationships among Epicrates (Boidae, Serpentes) , 1989 .

[79]  T. Smith,et al.  Ribosomal RNA gene sequences and hominoid phylogeny. , 1990, Molecular biology and evolution.

[80]  R. Jansen,et al.  Comparisons of phylogenetic hypotheses among different data sets in dwarf dandelions (Krigia, Asteraceae): Additional information from internal transcribed spacer sequences of nuclear ribosomal DNA , 1994, Plant Systematics and Evolution.

[81]  M. Donoghue,et al.  Phylogenetic relationships in Maloideae (Rosaceae): evidence from sequences of the internal transcribed spacers of nuclear ribosomal DNA and its congruence with morphology , 1995 .