Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity
- University of Pittsburgh, United States
- Howard Hughes Medical Institute, United States
- James Madison University, United States
- Albert Einstein College of Medicine, United States
Figures
Figure 1
Geographical distribution of sequenced mycobacteriophages.
(A) Locations of sequenced mycobacteriophages across the globe. (B) Locations of sequenced mycobacteriophages across the United States. Colors and letter designations on the isolates refer to the …
Figure 2 with 3 supplements
Nucleotide sequence comparison of 627 mycobacteriophages displayed as a dotplot.
Complete genome sequences of 627 mycobacteriophages were concatenated into a single file which was compared with itself using Gepard (Krumsiek et al., 2007) and displayed as a dotplot using default …
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Figure 2—source data 1
Concatenated DNA sequences for 627 phage genomes.
- https://doi.org/10.7554/eLife.06416.005
Figure 2—figure supplement 1
Dotplot of phages in Clusters I, N, P and the singleton Sparky.
A dotplot was generated using a concatenated file of genome sequences using Gepard (Krumsiek et al., 2007). The complexity of the genome relationships is illustrated by the Cluster I phages which …
Figure 2—figure supplement 2
Dotplot of Carcharodon, Che9c, Kheth, and Dori.
The dotplot of concatenated genome sequences illustrates the ambiguity of whether the singleton Dori warrants inclusion in Cluster B. Dori shares DNA sequence similarity with its closest relative …
Figure 2—figure supplement 3
Dotplot of Corndog, Brujita, SG4, Yoshi, and MooMoo.
The dotplot of concatenated genome sequences illustrates the complex relationships between the singleton MooMoo and other phages. MooMoo shares DNA sequence similarity with SG4 (Subcluster F1) and …
Figure 3
Network phylogeny of 627 mycobacteriophages based on gene content.
Genomes of 627 mycobacteriophages were compared according to shared gene content using the Phamerator (Cresawn et al., 2011) database Mykobacteriophage_627, and displayed using SplitsTree (Huson and …
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Figure 3—source data 1
Nexus file containing phamily assignments for 627 phage genomes.
- https://doi.org/10.7554/eLife.06416.011
Figure 4 with 2 supplements
Proportions of orphams in mycobacteriophage genomes.
The proportions of genes that are orphams (i.e., single-gene phamilies with no homologues within the mycobacteriophage dataset) are shown for each phage. The order of the phages is as shown in Supple…
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Figure 4—source data 1
Pham table containing phamily designations for 627 phage genomes.
- https://doi.org/10.7554/eLife.06416.013
Figure 4—figure supplement 1
Shared gene content between Dori, MooMoo, and other mycobacteriophages.
(A) Average percentages of phamilies shared between Dori and other mycobacteriophages. (B) Average percentages of phamilies shared between MooMoo and other mycobacteriophages. Genomes on the x axis …
Figure 4—figure supplement 2
Shared gene content between Gaia, Sparky, and other mycobacteriophages.
(A) Average percentages of phamilies shared between Gaia and other mycobacteriophages. (B) Average percentages of phamilies shared between Sparky and other mycobacteriophages. Genomes on the x axis …
Figure 5
Heat map representation of shared gene content among 627 mycobacteriophages.
The percentages of pairwise shared genes was determined using a Phamerator (Cresawn et al., 2011) database (Mykobacteriophage_627) populated with 627 completely sequenced phage genomes. The 69,574 …
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Figure 5—source data 1
Dataset showing percentages of pairwise shared phamilies.
- https://doi.org/10.7554/eLife.06416.017
Figure 6 with 2 supplements
Cluster diversity and isolation.
(A) The CLuster Averaged Shared Phamilies (CLASP; blue), Cluster Associated Phamilies (CAP; red) and Cluster Cohesion Index (CCI; green) values are plotted for each mycobacteriophage cluster. (B) …
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Figure 6—source data 1
Datasets showing numbers of CLuster Average Shard Phamilies.
- https://doi.org/10.7554/eLife.06416.019
Figure 6—figure supplement 1
Resampling CLASP values for cluster diversity and size.
CLuster Averaged Shared Phamilies (CLASP) values were calculated for Clusters A, B, C, E, F, and K by resampling random subsets of the genomes. The size of the subsets is shown on the x axis and …
Figure 6—figure supplement 2
Cluster diversity shown by Cluster-Associated Phamilies (CAP) and Cluster Phamily Variation (CPV) indices.
The CAP and CPV values are plotted for each cluster.
Figure 7
Rarefaction analysis of mycobacteriophage genomes.
(A) The numbers of phamilies are reported for between 1 and 627 phage genomes sampled at random without replacement; the mean of 10,000 iterations is shown in red; gray lines indicate a confidence …
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Figure 7—source data 1
Datasets for determination of rarefaction curves.
- https://doi.org/10.7554/eLife.06416.024
Tables
Table 1
Diversity and genetic isolation of mycobacteriophage genome clusters
| Cluster | # Subclusters | # Genomes | Average # genes* | Average length (bp) | Total phams† | Total genes | CLASP‡ | CAP§ | CCI# | CII¶ |
|---|---|---|---|---|---|---|---|---|---|---|
| A | 11 | 232 | 90 ± 5.3 | 51,514 | 1085 | 20,880 | 38.3 | 12.4 | 0.08 | 80.2 |
| B | 5 | 109 | 100.4 ± 4.5 | 68,653 | 421 | 10,944 | 66.2 | 23.2 | 0.24 | 81.0 |
| C | 2 | 45 | 231 ± 5.9 | 155,504 | 486 | 10,395 | 89.3 | 29.4 | 0.48 | 84.6 |
| D | 2 | 10 | 89.3 ± 6.4 | 64,965 | 147 | 893 | 88.1 | 64.3 | 0.61 | 71.4 |
| E | 1 | 35 | 141.9 ± 3.4 | 75,526 | 236 | 4967 | 87.2 | 63.8 | 0.60 | 59.3 |
| F | 3 | 66 | 105.3 ± 5.3 | 57,416 | 658 | 6950 | 54.4 | 4.9 | 0.16 | 55.8 |
| G | 1 | 14 | 61.5 ± 1.2 | 41,845 | 72 | 861 | 96.0 | 91.1 | 0.85 | 55.6 |
| H | 2 | 5 | 98.4 ± 5.7 | 69,469 | 207 | 492 | 61.6 | 31.5 | 0.48 | 67.6 |
| I | 2 | 4 | 78 ± 3.7 | 49,954 | 147 | 312 | 58.9 | 35.0 | 0.53 | 23.8 |
| J | 1 | 16 | 239.8 ± 9.3 | 110,332 | 530 | 3776 | 70.8 | 40.1 | 0.45 | 58.5 |
| K | 5 | 32 | 95.7 ± 4.6 | 59,720 | 411 | 3069 | 51.8 | 20.0 | 0.23 | 73.5 |
| L | 3 | 13 | 127.9 ± 6.5 | 75,177 | 246 | 1663 | 78.2 | 50.8 | 0.52 | 72.4 |
| M | 2 | 3 | 141 ± 8.8 | 81,636 | 201 | 423 | 73.5 | 63.0 | 0.70 | 69.2 |
| N | 1 | 7 | 69.1 ± 2.2 | 42,888 | 152 | 484 | 64.1 | 45.6 | 0.45 | 40.8 |
| O | 1 | 5 | 124.2 ± 3.1 | 70,651 | 151 | 621 | 90.6 | 83.3 | 0.82 | 64.2 |
| P | 2 | 9 | 78.8 ± 2.1 | 47,668 | 159 | 709 | 76.1 | 42.3 | 0.50 | 34.0 |
| Q | 1 | 5 | 85.2 ± 3.7 | 53,755 | 90 | 426 | 96.6 | 90.4 | 0.95 | 73.3 |
| R | 1 | 4 | 101.5 ± 2.5 | 71,348 | 117 | 406 | 91.4 | 84.8 | 0.87 | 71.8 |
| S | 1 | 2 | 109 ± 2.0 | 65,172 | 117 | 218 | 91.7 | 91.7 | 0.93 | 70.9 |
| T | 1 | 3 | 66.7 ± 2.4 | 42,833 | 83 | 200 | 86.1 | 82.5 | 0.80 | 62.7 |
| Dori | 1 | 1 | 94 | 64,613 | 94 | 94 | N/A | N/A | N/A | 35.8 |
| DS6A | 1 | 1 | 97 | 60,588 | 96 | 97 | N/A | N/A | N/A | 58.3 |
| Gaia | 1 | 1 | 194 | 90,460 | 193 | 194 | N/A | N/A | N/A | 58.0 |
| MooMoo | 1 | 1 | 98 | 55,178 | 98 | 98 | N/A | N/A | N/A | 31.6 |
| Muddy | 1 | 1 | 71 | 48,228 | 70 | 71 | N/A | N/A | N/A | 71.4 |
| Patience | 1 | 1 | 109 | 70,506 | 109 | 109 | N/A | N/A | N/A | 57.8 |
| Sparky | 1 | 1 | 93 | 63,334 | 93 | 93 | N/A | N/A | N/A | 48.4 |
| Wildcat | 1 | 1 | 148 | 78,296 | 148 | 148 | N/A | N/A | N/A | 69.6 |
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*
Average number of protein-coding genes per genome, with standard deviation.
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†
Total phams is the sum of all phamilies (groups of homologous mycobacteriophage genes) in that cluster.
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‡
The Cluster Averaged Shared Phamilies (CLASP) index is the average of the percentages of phamilies shared pairwise between genomes within a cluster.
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§
The Cluster-Associated Phamilies (CAP) index is the percentage of the average number of phamilies per genome within a cluster whose phamilies are present in every cluster member.
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#
The Cluster Cohesion Index (CCI) is generated by dividing the average number of genes per genome by the total number of phamilies (phams) in that cluster.
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¶
The Cluster Isolation Index (CII) is the percentage of phams that are present only in that cluster, and not present in other mycobacteriophages.
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N/A: Not applicable.
Table 2
Genometrics and Cluster Cohesion Indexes of mycobacteriophages
| Cluster | Subcluster | # Genomes | Average # genes | Average length (bp) | # Phams | CLASP* | CAP† | CCI‡ |
|---|---|---|---|---|---|---|---|---|
| A | 232 | 90.0 | 51,514 | 1085 | 38.3 | 12.4 | 8.0 | |
| A1 | 72 | 91.2 | 51,954 | 416 | 72.3 | 36.9 | 22.0 | |
| A2 | 28 | 93.4 | 52,805 | 312 | 64.7 | 30.1 | 30.0 | |
| A3 | 37 | 87.7 | 50,325 | 163 | 81.1 | 48.8 | 54.0 | |
| A4 | 46 | 87.4 | 51,376 | 125 | 92.7 | 70.6 | 70.0 | |
| A5 | 16 | 86.0 | 50,531 | 152 | 81.4 | 58.7 | 57.0 | |
| A6 | 11 | 97.8 | 51,677 | 128 | 90.2 | 75.1 | 76.0 | |
| A7 | 3 | 84.3 | 52,941 | 115 | 74.9 | 64.4 | 73.0 | |
| A8 | 4 | 97.8 | 51,597 | 107 | 93.5 | 86.8 | 91.0 | |
| A9 | 4 | 96.0 | 52,838 | 106 | 92.7 | 83.4 | 91.0 | |
| A10 | 7 | 80.0 | 49,174 | 112 | 81.6 | 60.9 | 71.0 | |
| A11 | 4 | 98.5 | 52,260 | 113 | 93.6 | 88.3 | 87.0 | |
| B | 108 | 100.4 | 68,653 | 421 | 66.2 | 23.2 | 24.0 | |
| B1 | 77 | 101.8 | 68,532 | 144 | 93.2 | 72.9 | 71.0 | |
| B2 | 8 | 89.9 | 67,267 | 101 | 94.9 | 84.6 | 89.0 | |
| B3 | 12 | 102.8 | 68,698 | 121 | 96.3 | 84.7 | 85.0 | |
| B4 | 8 | 96.1 | 70,619 | 166 | 79.9 | 45.8 | 58.0 | |
| B5 | 3 | 96.3 | 70,033 | 108 | 91.7 | 87.2 | 89.0 | |
| C | 45 | 231.0 | 155,504 | 486 | 89.3 | 29.4 | 48.0 | |
| C1 | 44 | 231.0 | 155,297 | 345 | 91.9 | 73.2 | 67.0 | |
| C2 | 1 | 229.0 | 164,602 | 227 | N/A | N/A | N/A | |
| D | 10 | 89.3 | 64,965 | 147 | 88.1 | 64.3 | 61.0 | |
| D1 | 9 | 87.3 | 64,697 | 100 | 94.9 | 88.8 | 87.0 | |
| D2 | 1 | 107.0 | 67,383 | 107 | N/A | N/A | N/A | |
| E | 35 | 141.9 | 75,526 | 235 | 87.2 | 63.8 | 60.0 | |
| F | 66 | 105.3 | 57,416 | 658 | 54.4 | 4.9 | 16.0 | |
| F1 | 60 | 104.8 | 57,486 | 573 | 59.6 | 20.6 | 18.0 | |
| F2 | 5 | 110.8 | 55,996 | 207 | 65.7 | 49.0 | 54.0 | |
| F3 | 1 | 107.0 | 60,285 | 105 | N/A | N/A | N/A | |
| G | 14 | 61.5 | 41,845 | 72 | 96.0 | 91.1 | 85.0 | |
| H | 5 | 98.4 | 69,469 | 207 | 61.6 | 31.5 | 48.0 | |
| H1 | 4 | 95.8 | 69,137 | 131 | 81.9 | 67.9 | 73.0 | |
| H2 | 1 | 109.0 | 70,797 | 110 | N/A | N/A | N/A | |
| I | 4 | 78.0 | 49,954 | 147 | 58.9 | 35.0 | 53.0 | |
| I1 | 3 | 76.0 | 47,588 | 101 | 77.5 | 66.7 | 75.0 | |
| I2 | 1 | 84.0 | 57,050 | 84 | N/A | N/A | N/A | |
| J | 16 | 239.8 | 110,332 | 530 | 70.8 | 40.1 | 45.0 | |
| K | 33 | 95.7 | 59,720 | 411 | 51.8 | 20.0 | 23.0 | |
| K1 | 15 | 94.3 | 59,877 | 166 | 85.5 | 47.9 | 57.0 | |
| K2 | 4 | 96.3 | 56,597 | 128 | 85.2 | 77.7 | 75.0 | |
| K3 | 3 | 98.2 | 61,322 | 111 | 92.2 | 89.5 | 88.0 | |
| K4 | 5 | 94.0 | 57,865 | 106 | 93.7 | 87.2 | 89.0 | |
| K5 | 6 | 98.2 | 62,154 | 144 | 82.1 | 68.2 | 68.0 | |
| L | 13 | 127.9 | 75,177 | 246 | 78.2 | 50.8 | 52.0 | |
| L1 | 3 | 123.7 | 74,050 | 135 | 92.6 | 88.8 | 92.0 | |
| L2 | 9 | 129.3 | 75,456 | 170 | 90.1 | 72.2 | 76.0 | |
| L3 | 1 | 128.0 | 76,050 | 126 | N/A | N/A | N/A | |
| M | 3 | 141.0 | 81,636 | 201 | 73.5 | 63.0 | 70.0 | |
| M1 | 2 | 135.0 | 80,593 | 138 | 96.6 | 96.6 | 98.0 | |
| M2 | 1 | 153.0 | 83,724 | 152 | N/A | N/A | N/A | |
| N | 7 | 69.1 | 42,888 | 152 | 64.1 | 45.6 | 45.0 | |
| O | 5 | 124.2 | 70,651 | 151 | 90.6 | 83.3 | 82.0 | |
| P | 9 | 78.8 | 47,668 | 159 | 76.1 | 42.3 | 50.0 | |
| P1 | 8 | 78.4 | 47,313 | 126 | 82.9 | 52.9 | 62.0 | |
| P2 | 1 | 82.0 | 50,513 | 82 | N/A | N/A | N/A | |
| Q | 5 | 85.2 | 53,755 | 90 | 96.6 | 90.4 | 95.0 | |
| R | 4 | 101.5 | 71,348 | 117 | 91.4 | 84.8 | 87.0 | |
| S | 2 | 109.0 | 65,172 | 117 | 91.7 | 91.7 | 93.0 | |
| T | 3 | 66.7 | 42,833 | 83 | 86.1 | 82.5 | 80.0 |
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*
Cluster Averaged Shared Phamilies.
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†
Cluster Associated Phamilies.
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‡
Cluster Cohesion Index.
Additional files
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Supplementary file 1
List of 627 sequenced mycobacteriophages and cluster designations.
- https://doi.org/10.7554/eLife.06416.025
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Supplementary file 2
Full list of group author details.
- https://doi.org/10.7554/eLife.06416.026
