- D Thybert, M Roller, FCP Navarro, I Fiddes, I Streeter, C Feig, D Martin-Galvez, M Kolmogorov, V Janoušek, W Akanni, B Aken, S Aldridge, V Chakrapani, W Chow, L Clarke, C Cummins, A Doran, M Dunn, L Goodstadt, K Howe, M Howell, AA Josselin, RC Karn, CM Laukaitis, L Jingtao, F Martin, M Muffato, S Nachtweide, MA Quail, C Sisu, M Stanke, K Stefflova, C Van Oosterhout, F Veyrunes, B Ward, F Yang, G Yazdanifar, A Zadissa, DJ Adams, A Brazma, M Gerstein, B Paten, S Pham, TM Keane, DT Odom, P Flicek. Repeat associated mechanisms of genome evolution and function revealed by the Mus caroli and Mus pahari genomes. Genome Res 2018;28(4):448–459. doi:10.1101/gr.234096.117
[BibTeX] [Abstract]
Understanding the mechanisms driving lineage-specific evolution in both primates and rodents has been hindered by the lack of sister clades with a similar phylogenetic structure having high-quality genome assemblies. Here, we have created chromosome-level assemblies of the Mus caroli and Mus pahari genomes. Together with the Mus musculus and Rattus norvegicus genomes, this set of rodent genomes is similar in divergence times to the Hominidae (human-chimpanzee-gorilla-orangutan). By comparing the evolutionary dynamics between the Muridae and Hominidae, we identified punctate events of chromosome reshuffling that shaped the ancestral karyotype of Mus musculus and Mus caroli between 3 and 6 million yr ago, but that are absent in the Hominidae. Hominidae show between four- and sevenfold lower rates of nucleotide change and feature turnover in both neutral and functional sequences, suggesting an underlying coherence to the Muridae acceleration. Our system of matched, high-quality genome assemblies revealed how specific classes of repeats can play lineage-specific roles in related species. Recent LINE activity has remodeled protein-coding loci to a greater extent across the Muridae than the Hominidae, with functional consequences at the species level such as reproductive isolation. Furthermore, we charted a Muridae-specific retrotransposon expansion at unprecedented resolution, revealing how a single nucleotide mutation transformed a specific SINE element into an active CTCF binding site carrier specifically in Mus caroli, which resulted in thousands of novel, species-specific CTCF binding sites. Our results show that the comparison of matched phylogenetic sets of genomes will be an increasingly powerful strategy for understanding mammalian biology.
@Article{29563166, author = {Thybert D and Roller M and Navarro FCP and Fiddes I and Streeter I and Feig C and Martin-Galvez D and Kolmogorov M and Janoušek V and Akanni W and Aken B and Aldridge S and Chakrapani V and Chow W and Clarke L and Cummins C and Doran A and Dunn M and Goodstadt L and Howe K and Howell M and Josselin AA and Karn RC and Laukaitis CM and Jingtao L and Martin F and Muffato M and Nachtweide S and Quail MA and Sisu C and Stanke M and Stefflova K and Van Oosterhout C and Veyrunes F and Ward B and Yang F and Yazdanifar G and Zadissa A and Adams DJ and Brazma A and Gerstein M and Paten B and Pham S and Keane TM and Odom DT and Flicek P}, title = {Repeat associated mechanisms of genome evolution and function revealed by the Mus caroli and Mus pahari genomes}, journal = {Genome Res}, volume = {28}, number = {4}, pages = {448--459}, year = {2018}, doi = {10.1101/gr.234096.117}, howpublished = {Advanced online publication: 21 March 2018}, note = {First posted as a preprint: 2 July 2017}, abstract = {Understanding the mechanisms driving lineage-specific evolution in both primates and rodents has been hindered by the lack of sister clades with a similar phylogenetic structure having high-quality genome assemblies. Here, we have created chromosome-level assemblies of the Mus caroli and Mus pahari genomes. Together with the Mus musculus and Rattus norvegicus genomes, this set of rodent genomes is similar in divergence times to the Hominidae (human-chimpanzee-gorilla-orangutan). By comparing the evolutionary dynamics between the Muridae and Hominidae, we identified punctate events of chromosome reshuffling that shaped the ancestral karyotype of Mus musculus and Mus caroli between 3 and 6 million yr ago, but that are absent in the Hominidae. Hominidae show between four- and sevenfold lower rates of nucleotide change and feature turnover in both neutral and functional sequences, suggesting an underlying coherence to the Muridae acceleration. Our system of matched, high-quality genome assemblies revealed how specific classes of repeats can play lineage-specific roles in related species. Recent LINE activity has remodeled protein-coding loci to a greater extent across the Muridae than the Hominidae, with functional consequences at the species level such as reproductive isolation. Furthermore, we charted a Muridae-specific retrotransposon expansion at unprecedented resolution, revealing how a single nucleotide mutation transformed a specific SINE element into an active CTCF binding site carrier specifically in Mus caroli, which resulted in thousands of novel, species-specific CTCF binding sites. Our results show that the comparison of matched phylogenetic sets of genomes will be an increasingly powerful strategy for understanding mammalian biology.},}
Description
Understanding the mechanisms driving lineage-specific evolution in both primates and rodents has been hindered by the lack of sister clades with a similar phylogenetic structure having high-quality genome assemblies. Here, we have created chromosome-level assemblies of the Mus caroli and Mus pahari genomes. Together with the Mus musculus and Rattus norvegicus genomes, this set of rodent genomes is similar in divergence times to the Hominidae (human-chimpanzee-gorilla-orangutan). By comparing the evolutionary dynamics between the Muridae and Hominidae, we identified punctate events of chromosome reshuffling that shaped the ancestral karyotype of Mus musculus and Mus caroli between 3 to 6 MYA, but that are absent in the Hominidae. In fact, Hominidae show between four- and seven-fold lower rates of nucleotide change and feature turnover in both neutral and functional sequences suggesting an underlying coherence to the Muridae acceleration. Our system of matched, high-quality genome assemblies revealed how specific classes of repeats can play lineage-specific roles in related species. For example, recent LINE activity has remodeled protein-coding loci to a greater extent across the Muridae than the Hominidae, with functional consequences at the species level such as reproductive isolation. Furthermore, we charted a Muridae-specific retrotransposon expansion at unprecedented resolution, revealing how a single nucleotide mutation transformed a specific SINE element into an active CTCF binding site carrier specifically in Mus caroli . This process resulted in thousands of novel, species-specific CTCF binding sites. Our results demonstrate that the comparison of matched phylogenetic sets of genomes will be an increasingly powerful strategy for understanding mammalian biology.
Full details are provided in our open access publication in Genome Research .
Data access
The genome assemblies of Mus caroli and Mus pahari were submitted to the European Nucleotide Archive and are available with accession numbers GCA_900094665 for Mus caroli and GCA_900095145 for Mus pahari . All reads from the ChIP-seq and RNA-seq experiments in this study were submitted to ArrayExpress and are available with accession numbers E-MTAB-5768 (RNA-seq) and E-MTAB-5769 (ChIP-seq).
Transposible element annotation
The results of RepeatMasker identifications were postprocessed to merge fragmented hits and remove non-transposable repeats to create the final set used in this study. The results of postprocessing are available here . The columns in the postprocessed files correspond to:
| Column number | Description |
|---|---|
| 1 | Toplevel genomic segment, i.e. chromosome, scaffold |
| 2 | Start position of match in genomic segment |
| 3 | End position of match in genomic segment |
| 4 | RepeatMasker result: % substitutions in matching region compared to the consensus |
| 5 | RepeatMasker result: % of bases opposite a gap in the query sequence (deleted bp) |
| 6 | RepeatMasker result: % of bases opposite a gap in the repeat consensus (inserted bp) |
| 7 | Transposable element classification: transposable element class |
| 8 | Transposable element classification: transposable element family |
| 9 | Transposable element classification: transposable element subfamily |
| 10 | Unique id created for this study |
Whole genome alignments
The whole genome alignments used in this study are available here in Ensembl Multi Format (EMF) and multiple alignment format (MAF). Pairwise whole genome alignments were generated using LastZ and multiple whole genome alignments with the Enredo-Pecan-Ortheus (EPO) pipeline. For more information please refer to the Methods in our paper .
CTCF occupancy sites
The peak sets per biological replicate are available in ArrayExpress under the accession number E-MTAB-5769 . The peaks present in at least two biological replicates are available here . The B2_Mm1 transposable elements used as input for building the neighbour joining tree are available here . For more information please refer to the Methods in our paper .
CTCF occupancy sites associated with repetitive elements are available here . The columns in the postprocessed files describe:
| Column name | Description |
|---|---|
| PeakChr | Toplevel genomic segment containing the CTCF peak, i.e. chromosome, scaffold |
| PeakStart | Start position of CTCF peak in genomic segment |
| PeakEnd | End position of CTCF peak in genomic segment |
| RepeatChr | Toplevel genomic segment containing the repeat element, i.e. chromosome, scaffold consensus |
| RepeatStart | Start position of repeat element in genomic segment |
| RepeatEnd | End position of repeat element in genomic segment |
| RepeatClass | Transposable element classification: transposable element class |
| RepeatFamily | Transposable element classification: transposable element family |
| RepeatSubfamily | Transposable element classification: transposable element subfamily |
Results of multiple alignments of CTCF sites between the rodents are available here . The name of the file corresponds to the species which was used as query to align to other species. The first column contains all CTCF sites from the query species, and each following column an alignment to another species. If a column contains genomic coordinates, a bound CTCF site is aligned. A lack of aligned CTCF sites is marked with an “X”. A row with “X” in all columns except the first represents a species-specific CTCF binding site. The position of peaks is in “Chr:Start-End” format.
Mus pahari breakpoints
chr1: mm_7:27,524,252-end + mm_19:start-end
chr2: mm_5:start-30,341,378 + mm_6:strt-end
chr3: mm_2:23,133,000-end
chr4: mm_3:start-end
chr5: mm_1:18,015,577-end
chr6: mm_4:45,383,207-end
chr7: mm_12:start-end
chr8: mm_14:start-end
chr9: mm_10:33,415,951-end
chr10: mm_9:start-end
chr11: mm_13:[66,989,676/67,139,392]-end + mm_15:start-32,682,454
chr12: mm_16:start-end
chr13: mm_11:start-31,004,372+mm_5:33,090,849-[109,638,275/110,356,165]
chr14: mm_11:31,014,735-end
chr15: mm_18:start-end
chr16: mm_2:start-23,116,788 + mm_13:start-[66,989,676/67,139,392]
chr17: mm_15:32,682,454-end
chr18: mm_17:31,811,330-end
chr19: mm_7:start-27,524,252+ mm_8:start-75,294,883
chr20: mm_8:75,299,631-end
chr21: mm_17:start-27,052,643 + mm_10:start-33,381,753
chr22: mm_1:start-17,966,305 + mm_4:start-45,383,207-end
chr23: mm_5:[109,638,275/110,356,165]-end
The above lines refer to the composition of the Music pahari chromosomes. For example, chr1 of Mus pahari is composed of chr7 of Mus musculus starting from the position 27,524,252 until the end and then chr19 of Mus musculus from start to end. This gives a break point from the Mus musculus perspective.
For data points such as [66,989,676/67,139,392], this results from the array CGH being done twice. We have the mean between these two values for the analysis of repeat enrichment in the paper.
Mouse-rat breakpoints
chr1 rn_5:start-13Mb + rn_9:24-104Mb + rn_13:start-end
chr2:rn_17:70Mb-end + rn_3:start-end
chr3:rn_2:87Mb-end
chr4:rn_5:16Mb- end
chr5:rn_4:start-28Mb + rn_14:start-83Mb + rn_chr12:start-end
chr6: rn_chr4:28Mb-end
chr7:rn_1:63Mb-218Mb
chr8:rn_16:19Mb-end+ rn_19:start-end
chr9:rn_8:start-end
chr10:rn_1:start-44Mb+ rn_20:10Mb-end+rn_7:start-67Mb
chr11:rn_14:83Mb-end + rn_10:15Mb-end
chr12:rn_6:27Mb-end
chr13:rn_17:start-70Mb + rn_2:start-51Mb
chr14:rn_15:start-23Mb + rn_16:start-18Mb + rn_15:23Mb-end
chr15:rn_2:52Mb-86Mb + rn_7:71Mb-end
chr16:rn_10:start-12Mb + rn_11:start-end
chr17:rn_1:44Mb-62Mb + rn_20:start-10Mb + rn_9:start-24Mb +rn_9:104Mb-end + rn_6:start-25Mb
chr18:rn_17:54Mb-62Mb + rn_18:start-end
chr19:rn_1:218Mb-end
The mouse rat synteny breaks have been defined using the Ensembl synteny tool . In order to match the chromosome painting resolution we only retained breaks involved in inter-chromosome rearrangement involved in rearrangement with a size of 5Mb or more.