Phylogenomics of Snakes


Reduced representation genome sequencing has ushered in new methods for understanding how life evolved on earth. These methods utilise genetic data in the form of dozens, hundreds or even thousands of loci to estimate phylogenetic relationships. This approach, often termed phylogenomic analysis, has the potential to resolve controversial evolutionary relationships, particularly among ancient, rapid radiations. Among vertebrates, phylogenomic analyses are increasingly applied to an iconic group of reptiles, snakes. Phylogenomic analyses of snakes have begun to shed light on long‐standing questions including relationships among snake families, their origin among squamate reptiles and putative causes of speciation within recent radiations. In addition, these methods may even be used to obtain genetic data from archival museum specimens. This emerging approach for understanding snake evolution will be improved by whole genome sequencing initiatives that include a diverse group of snake species.

Key Concepts

  • Snakes are important study systems for human physiology and medicine.
  • Snakes are important predators in ecosystems/important to maintaining ecosystem health.
  • Robust phylogenetic hypotheses are necessary to understand snake evolution.
  • Genome‐wide data offer unprecedented opportunities to resolve snake phylogeny and the tree of life.
  • Phylogenomic analyses of snakes will aid biologists and medical researchers worldwide.

Keywords: evolutionary trees; phylogenetic inference; herpetology; serpentes; genomics

Figure 1. Number of articles using the terms ‘phylogenomic’ and ‘snakes’ since 1995. These estimates were obtained using filtered Google Scholar searches in early 2017.
Figure 2. Graphical representation of methods used to acquire phylogenomic data sets from snakes. All methods require obtaining genetic samples from snake tissues/cells (a) and subsequent DNA (deoxyribonucleic acid) extraction (b). Genomic DNAs are then processed to reduce the size of the genome and generate data sets that can be compared in phylogenetic contexts. Three primary methods for generating phylogenomics data sets are (1) using oligonucleotide primers and polymerase chain reaction amplification (c), (2) restriction enzyme digestion (RADseq; d) and (3) targeted sequence capture (e). For illustrative purposes, in (d) we have depicted the use of the HaeIII endonuclease (restriction enzyme), which has a 4‐nucleotide recognition site of GGCC.
Figure 3. Phylogeny of snake families analysed by Streicher and Wiens (; modified from their Figure 4A) demonstrating the application of phylogenomic methods across snakes. Families with more than one species in the phylogeny have been collapsed. See text for description of different methodologies. Coding refers to the methodology of Schott et al. . A question mark indicates a branch (placement of uropletids + cylindrophiids) that the likelihood and species‐tree (multispecies coalescent) analyses of Streicher and Wiens disagreed upon. An asterisk indicates that scolecophidians are not recovered as monophyletic in all analyses.


Brahma RK, McCleary RJ, Kini RM and Dole R (2015) Venom gland transcriptomics for identifying, cataloging, and characterizing venom proteins in snakes. Toxicon 93: 1–10.

Cadle JE (1984) Molecular systematics of xenodontine colubrid snakes: I. South American xenodontines. Herpetologica 40: 8–20.

Card DC, Schield DR, Adams RH, et al. (2016) Phylogeographic and population genetic analyses reveal multiple species of Boa and independent origins of insular dwarfism. Molecular Phylogenetics and Evolution 102: 104–116.

Castoe TA, Braun EL, Bronikowski AM, et al. (2012) Report from the first snake genomics and integrative biology meeting. Standards in Genomic Sciences 7: 1.

Castoe TA, de Koning APJ, Hall KT, et al. (2013) The Burmese python genome reveals the molecular basis for extreme adaptation in snakes. Proceedings of the National Academy of Sciences of the United States of America 110: 20645–20650.

Chen X, Lemmon AR, Lemmon EM, Pyron RA and Burbrink FT (2017) Using phylogenomics to understand the link between biogeographic origins and regional diversification in ratsnakes. Molecular Phylogenetics and Evolution 111: 206–218.

Crawford NG, Faircloth BC, McCormack JE, et al. (2012) More than 1000 ultraconserved elements provide evidence that turtles are the sister group of archosaurs. Biology Letters 8: 783–786.

Diochot S, Baron A, Salinas M, et al. (2012) Black mamba venoms target acid‐sensing ion channels to abolish pain. Nature 490: 553–556.

Douglas DA and Gower DJ (2010) Snake mitochondrial genomes: phylogenetic relationships and implications of extended taxon sampling for interpretations of mitogenomic evolution. BMC Evolutionary Biology 11: 14.

Faircloth BC, McCormack JE, Crawford NG, et al. (2012) Ultraconserved elements anchor thousands of genetic markers for target enrichment spanning multiple evolutionary timescales. Systematic Biology 61: 717–726.

Figueroa A, McKelvy AD, Grismer LL, Bell CD and Lailvaux SP (2016) A species‐level phylogeny of extant snakes with description of a new colubrid subfamily and genus. PLoS One 11: e0161070.

Gower DJ and Winkler JD (2007) Taxonomy of the Indian snake Xylophis beddome (Serpentes: Caenophidia), with description of a new species. Hamadryad 31: 315–329.

Guibé J (1958) Les serpents de madagascar. Mémoires l'Institut Sci Madagascar (sér A. Biologie Animale 12: 189–260.

Head JJ, Bloch JI, Hastings K, et al. (2009) Giant boid snake from the Paleocene neotropics reveals hotter past equatorial temperature. Nature 457: 715–717.

Hsiang AY, Field DJ, Webster TH, et al. (2015) The origin of snakes: revealing the ecology, behavior, and evolutionary history of early snakes using genomics, phenomics, and the fossil record. BMC Evolutionary Biology 15: 87.

Irisarri I, Baurain D, Brinkmann H, et al. (2017) Phylotranscriptomic consolidation of the jawed vertebrate timetree. Nature Ecology and Evolution 1: 1370–1378.

Jennings WB (2017) Phylogenomic Data Acquisition: Principles and Practice. Boca Raton FL, USA: CRC Press.

Kerkkamp HMI, Kini RM, Pospelov AS, et al. (2016) Snake genome sequencing: results and future prospects. Toxins 8: 360.

Kelly CMR, Barker NP and Villet MH (2003) Phylogenetics of advanced snakes (Caenophidia based on four mitochondrial genes. Systematic Biology 52: 439–459.

Lawson R, Slowinski JB, Crother BI and Burbrink FT (2005) Phylogeny of the colubroidea (Serpentes): new evidence from mitochondrial and nuclear genes. Molecular Phylogenetics and Evolution 37: 581–601.

Leaché AD, Chavez AS, Jones LN, et al. (2015) Phylogenomics of phrynosomatid lizards: conflicting signals from sequence capture versus restriction site associated DNA sequencing. Genome Biology and Evolution 7: 706–719.

Lemmon AR, Emme S and Lemmon EC (2012) Anchored hybrid enrichment for massively high‐throughput phylogenomics. Systematic Biology 61: 727–744.

McDowell SB (1970) On the status and relationships of the Solomon Island elapid snakes. Journal of Zoology 161: 145–190.

McDowell SB (1985) The terrestrial Australian elapids: general summary. In: Grigg G, Shine R and Ehmann H (eds) The Biology of Australasian Frogs and Reptiles, pp. 261–264. Sydney: Royal Zoological Society of New South Wales.

McDowell SB (1987) Systematics. In: Seigel RA, Collins JT and Novak SS (eds) Snakes, Ecology and Evolutionary Biology, pp. 3–50. New York: McGraw‐Hill Publishing Co.

Meik JM, Fontenot BE, Franklin CJ and King C (2008) Apparent natural hybridization between the rattlesnakes Crotalus atrox and C. horridus. The Southwestern Naturalist 53: 196–200.

Meik JM, Streicher JW, Lawing AM, Flores‐Villela O and Fujita MK (2015) Limitations of climatic data for inferring species boundaries: insights from speckled rattlesnakes. PLoS One 10: e0131435.

Murphy JC, Mumpuni and Sanders KL (2011) First molecular evidence for the phylogenetic placement of the enigmatic snake genus Brachyorrhos (Serpentes: Caenophidia). Molecular Phylogenetics and Evolution 61: 953–957.

Pyron RA, Burbrink FT, Colli GR, et al. (2011) The phylogeny of advanced snakes (Colubroidea), with discovery of a new subfamily and comparison of support methods for likelihood trees. Molecular Phylogenetics and Evolution 58: 329–342.

Pyron RA, Hendry CR, Chou VM, et al. (2014) Effectiveness of phylogenomic data and coalescent species‐tree methods for resolving difficult nodes in the phylogeny of advanced snakes (Serpentes: Caenophidia). Molecular Phylogenetics and Evolution 81: 221–231.

Pyron RA, Hsieh FW, Lemmon AR, Lemmon Moriarty E and Hendry CR (2016) Integrating phylogenomic and morphological data to assess candidate species‐delimitation models in Brown and Red‐bellied snakes (Storeria). Zoological Journal of the Linnean Society 177: 937–949.

Reeder TW, Townsend TM, Mulcahy DG, et al. (2015) Integrated analyses resolve conflicts over squamate reptile phylogeny and reveal unexpected placements for fossil taxa. PLoS One 10: e0118199.

Reyes‐Velasco J, Meik JM, Smith EN and Castoe TA (2013) Phylogenetic relationships of the enigmatic longtailed rattlesnakes (Crotalus ericsmithi, C. lannomi, and C. stejnegeri). Molecular Phylogenetics and Evolution 69: 524–534.

Reynolds RG, Niemiller ML and Revell LJ (2014) Toward a tree‐of‐life for the boas and pythons: multilocus species‐level phylogeny with unprecedented taxon sampling. Molecular Phylogenetics and Evolution 71: 201–213.

Ruane S, Bryson RW, Pyron RA and Burbrink FT (2014) Coalescent species delimitation in milksnakes (genus Lampropeltis) and impacts on phylogenetic comparative analyses. Systematic Biology 63: 231–250.

Ruane S, Raxworthy CJ, Lemmon AR, Lemmon Moriarty E and Burbrink FT (2015) Comparing species‐tree estimation with large anchored phylogenomic and small Sanger‐sequenced molecular datasets: an empirical study on Malagasy pseudoxyrhophiine snakes. BMC Evolutionary Biology 15: 221.

Ruane S and Austin CC (2017) Phylogenomics using formalin‐fixed and 100+ year old intractable natural history specimens. Molecular Ecology Resources 17: 1003–1008.

Schield DR, Card DC, Adams RH, et al. (2015) Incipient speciation with biased gene flow between two lineages of the Western diamondback rattlesnake (Crotalus atrox). Molecular Phylogenetics and Evolution 83: 213–223.

Schott RK, Panesar B, Card DC, et al. (2017) Targeted capture of complete coding regions across divergent species. Genome Biology and Evolution 9: 398–414.

Simmons JE (2014) Fluid Preservation: A Comprehensive Reference. Lanham, MD: Rowman & Littlefield.

Simões BF, Simpaio FL, Douglas RH, et al. (2016) Visual pigments, ocular filters and the evolution of snake vision. Molecular Biology and Evolution 33: 2483–2495.

Singhal S, Grundler M, Colli G and Rabosky DL (2017) Squamate Conserved Loci (SqCL): A unified set of conserved loci for phylogenomics and population genetics of squamate reptiles. Molecular Ecology Resources 17: e12–e24.

Streicher JW and Wiens JJ (2016) Phylogenomic analyses reveal novel relationships among snake families. Molecular Phylogenetics and Evolution 100: 160–169.

Streicher JW and Wiens JJ (2017) Phylogenomic analyses of more than 4000 nuclear loci resolve the origin of snakes among lizard families. Biology Letters 13: 20170393.

Strickland JL, Carter S, Kraus F and Parkinson CL (2016) Snake evolution in Melanesia: origin of the Hydrophiinae (Serpentes, Elapidae), and the evolutionary history of the enigmatic New Guinean elapid Toxicocalamus. Zoological Journal of the Linnean Society 178: 663–678.

Van Strein JW and Isbell LA (2017) Snake scales, partial exposure, and the Snake Detection Theory: a human event‐related potentials study. Scientific Reports 7: 46331.

Vidal N and Hedges SB (2005) The phylogeny of squamate reptiles (lizards, snakes, and amphisbaenians) inferred from nine nuclear protein‐coding genes. Comptes Rendus Biologies 323: 1000–1008.

Vonk FJ, Caswell NR, Henkel C, et al. (2013) The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system. Proceedings of the National Academy of Sciences of the United States of America 110: 20651–20656.

Wiens JJ, Hutter CR, Mulcahy DG, et al. (2012) Resolving the phylogeny of lizards and snakes (Squamata) with extensive sampling of genes and species. Biology Letters 8: 1043–1046.

Wüster W, Thorpe RS, Cox MJ, Jintakune P and Nabhitabhata J (1995) Population systematics of the snake genus Naja (Reptilia: Serpentes: Elapidae) in Indochina: Multivariate morphometrics and comparative mitochondrial DNA sequencing (cytochrome oxidase I). Journal of Evolutionary Biology 8: 493–510.

Zinenko O, Sovic M, Joger U and Gibbs HL (2016) Hybrid origin of European Vipers (Vipera magnifica and Vipera orlovi) from the Caucasus determined using genomic scale DNA markers. BMC Evolutionary Biology 16: 76.

Further Reading

Arnold B, Corbett‐Detig RB, Hartl D and Bomblies K (2013) RADseq underestimates diversity and introduces genealogical biases due to nonrandom haplotype sampling. Molecular Ecology 22: 3179–3190.

Brown JM and Thomson RC (2017) Bayes factor unmask highly variable information content, bias, and extreme influence in phylogenomic analysis. Systematic Biology 66: 517–530.

Cariou M, Duret L and Charlat S (2013) Is RAD‐seq suitable for phylogenetic inference? An in silico assessment and optimization. Ecology and Evolution 3: 846–852.

Davey JW and Blaxter ML (2011) RADseq: next‐generation population genetics. Briefings in Functional Genomics 9: 416–423.

Mulcahy DG, Noonan BP, Moss T, et al. (2012) Estimating divergence dates and evaluating dating methods using phylogenomic and mitochondrial data in squamate reptiles. Molecular Phylogenetics and Evolution 65: 974–991.

Philippe H, Delsuc F, Brinkmann H and Lartillot N (2005) Phylogenomics. Annual Review of Ecology, Evolution, and Systematics 36: 541–562.

Pyron RA (2016) Novel approaches for phylogenetic inference from morphological data and total‐evidence dating in squamate reptiles (lizards, snakes, and amphisbaenians). Systematic Biology 66: 38–56.

Reid NM, Hird SM, Brown JM, et al. (2013) Poor fit to the multispecies coalescent is widely detectable in empirical data. Systematic Biology 63: 322–333.

Streicher JW, Schulte JA II and Wiens JJ (2016) How should genes and taxa be sampled for phylogenomic analyses with missing data? An empirical study in iguanian lizards. Systematic Biology 65: 128–145.

Zheng Y and Wiens JJ (2016) Combining phylogenomic and supermatrix approaches, and a time‐calibrated phylogeny for squamate reptiles (lizards and snakes) based on 52 genes and 4162 species. Molecular Phylogenetics and Evolution 94: 537–547.

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How to Cite close
Streicher, Jeffrey W, and Ruane, Sara(Feb 2018) Phylogenomics of Snakes. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0027476]