19, 462471 (2002), Singer, A. G., Macrides, F., Clancy, A. N. & Agosta, W. C. Purification and analysis of a proteinaceous aphrodisiac pheromone from hamster vaginal discharge. PubMed The poster included with this issue provides a high-level view of the mouse genome, showing such features as genes and gene predictions, repetitive sequence content, (G+C) content, synteny with the human genome, and mouse QTLs. 27; if a typical gene contains a few such regulatory sequences, there may be tens to hundreds of thousands of such elements. Notably, the neutral substitution rate is lowest for chromosome X. ), Back ground info, characters and plot summary, Harold Levine, Norman Levine, Robert T. Levine, Glencoe Language Arts: Grammar and Language Workbook, Grade 9, Vocabulary for Achievement: Fourth Course, myPerspectives: Grade 10, Volume 2 California Edition. We suggested a range of 30,00040,000 to allow for additional genes. For you to conduct a comparative analysis, you need different types of comparison charts and graphs. This probably corresponds to a smaller number of actual new genes, because some of these may belong to the same transcription unit as an adjacent de novo or evidence-based prediction. Although the wind has blown down the walls of the mouses nest, or housie, it does not have the materials to make a new one. 12, 2636 (2002), Thiery, J. P., Macaya, G. & Bernardi, G. An analysis of eukaryotic genomes by density gradient centrifugation. Furthermore, key mouse genome databases were developed at the Jackson (http://www.informatics.jax.org/), Harwell (http://www.har.mrc.ac.uk/) and RIKEN (http://genome.rtc.riken.go.jp/) laboratories to provide the community with access to this information. A higher rate of interspersed repeat insertion does not explain the larger size of the human genome. The most notable difference is in the changing rate of transposition over time: the rate has remained fairly constant in mouse, but markedly increased to a peak at about 40Myr in human, and then plummeted. The proportion of mouse genes without any homologue currently detectable in the human genome (and vice versa) seems to be less than 1%. As the embryo transits from pre- to post-implantation, major structural and transcriptional changes occur within the embryonic lineage to set up the basis for the subsequent phase of gastrulation. Curr. Approximately 83% of the exons in the catalogue were detected by SGP2, which predicted an additional 9,808 (6%) new exons. Regions containing predicted domains had higher average percentage identities and lower KA/KS values than regions without predicted domains or than full-length proteins (Fig. Genome-wide alignments also allow us to investigate how the patterns of neutral substitution, deletion and insertion vary across the genome, providing an insight on the underlying mutational processes. according to the speaker's sentiments, explain why the mouse is not alone in his troubles neither mice or men can predict the future and cannot predict when things will go wrong. To do this, we estimated the proportion of the genome that is better conserved than would be expected given the underlying neutral rate of substitution. Evol. Most notably, differences in divergence levels are not affected by phylogenetic assumptions, as the time spent by an ancestral repeat family in either lineage is necessarily identical. Mamm. We also compared the sequence reported here to a draft sequence of mouse chromosome 16 recently published by Mural and co-workers45. These methods tended to have significant overlap with the above-generated gene catalogues, but each tended to introduce significant numbers of predictions that were unsupported by other methods and that appeared to be false positives. Evol. Perhaps these represent functional CpG islands, a proposition that can now be tested experimentally84. They often exhibit similar behaviour across a human chromosome, as seen for human chromosome 22 (Fig. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Reprod. Subsequent efforts filled out the map to over 12,000 polymorphic markers, although not all of these loci have been positioned precisely relative to one another. Comparative analysis of the gene-dense ACHE/TFR2 region on human chromosome 7q22 with the orthologous region on mouse chromosome 5. Chromosome X shows an excess of L1 copies, but not a marked excess of either full-length L1 or LTR copies. Animals. A total of 7,293 amino acid variants reported to be disease-associated190 were mapped to corresponding positions in the mouse sequence. contracts here. Endocrinology 141, 833838 (2000), Campbell, S. M., Rosen, J. M., Hennighausen, L. G., Strech-Jurk, U. 2022 Aug;111:135-147. doi: 10.1016/j.reprotox.2022.05.012. we performed a comparative proteomics analysis of obstructed kidneys from pediatric patients with ureteropelvic junction obstruction (UPJO) and healthy kidney tissues. Significant experimental evidence came from genetic studies of somatic cells69. Genome Res. Overall, about 72% of proteins contained at least one InterPro domain. Acta 1482, 249258 (2000), Briand, L. et al. Stochastic patterning in the mouse pre-implantation embryo. Google Scholar, O'Brien, S. J. et al. An encyclopedia of mouse genes. Deeper understanding of the biology of transposable elements and detailed knowledge of interspersed repeat populations in other mammals should clarify these issues. Gene 276, 313 (2001), The SNP Consortium An SNP map of the human genome generated by reduced representation shotgun sequencing. In fact, the proportion is broadly consistent with what would be expected given the probable rate of turnover of sequence in the mouse and human genomes. Proc. Genome 9, 491495 (1998), Ferretti, V., Nadeau, J. H. & Sankoff, D. Combinatorial Pattern Matching, 7th Annual Symposium (eds Hirschberg, D. & Myers, G.) 159167 (Springer, Berlin, 1996), Bourque, G. & Pevzner, P. A. Genome-scale evolution: reconstructing gene orders in the ancestral species. Car factories can leverage this analysis to examine two production processes to determine cost-effectiveness. The site is secure. Sselected is the difference between the blue density and the red component, and thus represents a scaled version of Sselected, the predicted density for conservation scores of 50-bp windows in the human genome that are evolving under selection. Int J Mol Sci. Q. Rev. The relatively high values of KA/KS may reflect both positive selection (as genes diverge to take up new function) and the accumulation of mutations in moribund or dead genes. How informative is the mouse for human gut microbiota research? Genomics 15, 507514 (1993), Parham, P. Virtual reality in the MHC. Hundreds of new mutants with biochemical, development and behavioural phenotypes are being generated each year. In particular, t4D increases more sharply with high (G+C) content, whereas tAR does not show as much divergence. Arch. This proportion is much higher than can be explained by protein-coding sequences alone, implying that the genome contains many additional features (such as untranslated regions, regulatory elements, non-protein-coding genes, and chromosomal structural elements) under selection for biological function. Biol. & Todd, J. (in the press), Bernardi, G. The human genome: organization and evolutionary history. Nature 420, 582586 (2002), Blake, D. J., Weir, A., Newey, S. E. & Davies, K. E. Function and genetics of dystrophin-related proteins in muscle. The longer you take, the less valuable these improvements become. Internet Explorer). We required that at least 50bp be aligned in each window. Nature Rev. This is the case as the speaker would never rin an chase the little beastie. He has no desire to chase after, and murder the mouse with a pattle. He is not like those the mouse has come to fear. If you encounter an assignment that fails to provide a frame of reference, you must come up with one on your own. It remains an important challenge to unravel the mechanistic basis and evolutionary consequences of such variation. To improve discrimination of functional tRNA genes, we exploited comparative genomic analysis of mouse and human. A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome. Phys Biol. The median divergence levels of 18 subfamilies of interspersed repeats that were active shortly before the humanrodent speciation (Table 6) indicates an approximately twofold higher average substitution rate in the mouse lineage than in the human lineage, corresponding closely to an early estimate by Wu and Li109. Our gene catalogue contains 656 of these gene predictions, indicating extensive agreement between these two independent analyses. 12, 315 (2002), Toyoda, A. et al. Simulation experiments show that DNA sequences subjected to random mutation at the neutral rate that has occurred between the human and mouse genomes (see below) can still be readily aligned by computer. Genet. Not all mouse models replicate the human phenotype in the expected way. These cDNAs are very short on average, with few exons (median 2) and small ORFs (average length of 85 amino acids); whereas some of these may be true genes, most seem unlikely to reflect true protein-coding genes, although they may correspond to RNA genes or other kinds of transcripts. In an accompanying paper, Dermitzakis and colleagues show that a large number of conserved sequences on human chromosome 21 are actively conserved but are unlikely to be genes, suggesting that a large number of non-coding sequence are under selection247. 61, 155163 (2002), Sutton, K. A. The assembly generated by Arachne was chosen as the draft sequence described here because it yielded greater short-range and long-range continuity with comparable accuracy. In addition to the genome-wide efforts of the MGSC, other publicly funded groups have been contributing to the sequencing of the mouse genome in specific regions of biological interest. Proc. Sci. Closer analysis, however, shows that this is not the case. Your introduction will include your frame of reference, grounds for comparison, and thesis. 16). Res. J. Mol. The existence of four families in mouse provides independent opportunities to investigate the properties of SINEs (see below). Funding:NIHs National Human Genome Research Institute (NHGRI), National Institute of General Medical Sciences (NIGMS), National Cancer Institute (NCI), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Environmental Health Sciences (NIEHS), National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH), National Institute of Neurological Disorders and Stroke (NINDS), and NIH Common Fund; Spanish Plan Nacional; Wellcome Trust; Howard Hughes Medical Institute; National Science Foundation; and the American Recovery and Reinvestment Act. In other words, the substitution rate seems to be higher in regions of extremely high or low (G+C) content, with the sign of the correlation differing in regions with high versus low (G+C) content. The observed base changes can be used to infer the underlying substitution rate, which includes back mutations, by using various continuous-time Markov models230. Here, we review the current knowledge of mammalian development of both mouse and human focusing on morphogenetic processes leading to the onset of gastrulation, when the embryonic anterior-posterior axis becomes established and the three germ layers start to be specified. We measured the impact of the higher substitution rate in mouse on the ability to detect ancestral repeats in the mouse genome. Cheng Y, Ma Z, Kim BH, Wu W, Cayting P, Boyle AP, Sundaram V, Xing X, Dogan N, Li J, Euskirchen G, Lin S, Lin Y, Visel A, Kawli T, Yang X, Patacsil D, Keller CA, Giardine B; Mouse ENCODE Consortium, Kundaje A, Wang T, Pennacchio LA, Weng Z, Hardison RC, Snyder MP. Note that, for the same (G+C) content, L1 density is 1.5- to twofold higher on the sex chromosomes. 149, 441451 (1991), Gu, X. You have full access to this article via your institution. . The filtering process thus removed 24-fold more apparent false positives than true positives. He will give the mouse his blessin through the food it steals. J. Biol. The grounds for comparison anticipates the comparative nature of your thesis. The distribution of SNPs reveals that genetic variation among mouse strains occurs in large blocks, mostly reflecting contributions of the two subspecies Mus musculus domesticus and Mus musculus musculus to current laboratory strains. The latter have been used for deriving large sets of BAC-end sequences37 and, as part of this collaboration, to generate a fingerprint-based physical map44. Frame of Reference. Comparative analysis of human and mouse development: From zygote to pre-gastrulation January 2019 Current Topics in Developmental Biology 136 DOI: 10.1016/bs.ctdb.2019.10.002 In book: Current. Sneutral is a scaled version of the Sneutral density from the blue curve in Fig. 369, 110 (1999), Lane, R. P. et al. 167, 4558 (1999), Ichikawa, T., Itakura, T. & Negishi, M. Functional characterization of two cytochrome P-450s within the mouse, male-specific steroid 16 alpha-hydroxylase gene family: expression in mammalian cells and chimeric proteins. Lab. Sci. You can avoid this effect by grouping more than one point together, thereby cutting down on the number of times you alternate from A to B. Evol. Although we do not have a corresponding direct estimate of large-scale deletions in the mouse lineage, the predicted rate of about 45% is roughly twice as high as for the human lineage, which is similar to the ratio seen for nucleotide substitutions. The colour codes are indicated in the lower-right panel. Certain classes of secreted proteins implicated in reproduction, host defence and immune response seem to be under positive selection, which drives rapid evolution. LINE-1 (L1) lineages in the mouse. The extant L1 elements in both species derive from a common ancestor (L1MA6 in Table 6) by means of a series of subfamilies defined primarily by the rapidly evolving 3 non-coding sequences110. Genome-wide comparisons among organisms can also highlight key differences in the forces shaping their genomes, including differences in mutational and selective pressures13,14. & Cross, J. C. Placental development: lessons from mouse mutants. At the nucleotide level, approximately 40% of the human genome can be aligned to the mouse genome. It is universal that plans will fall apart. We recognize this assumption is not strictly valid but nonetheless is a reasonable starting point. Dev. To obtain Other chromosomes, however, show evidence of much more extensive interchromosomal rearrangement than these cases (Fig. You can supercharge your Excel by installing a particular add-in to access ready-made graphs for comparative analysis. 14, 823828 (1997), Bernardi, G. et al. Bengaluru Area, India. The RefSeq database was used to define gene features. Rev. Sequence identity rises gradually from a background level to 78% near the approximate transcription start site, where the level reaches a plateau. Human chromosome 19 and related regions in mouse: conservative and lineage-specific evolution. 28, 351359 (1997), Sundseth, S. S. & Waxman, D. J. Sex-dependent expression and clofibrate inducibility of cytochrome P450 4A fatty acid omega-hydroxylases. Chromosomal location in mouse is shown on each of the branches for each subfamily. SURYA VARDHAN BHAMIDIPATI auf LinkedIn: A Comparative Analysis of official website and that any information you provide is encrypted Loss-of-heterozygosity analysis of small-cell lung carcinomas using single-nucleotide polymorphism arrays. Genome Res. Trends Genet. He hallucinates seeing Aunt Clara and a giant, talking rabbit. Functional annotation of a full-length mouse cDNA collection. Singer, Jade P. Vinson, Claire M. Wade, Michael C. Zody, Ewan Birney, Nick Goldman, Arkadiusz Kasprzyk, Guy Slater, Arne Stabenau, Simon Whelan, Michele Clamp, James Cuff, Val Curwen, Tim Cutts, Eduardo Eyras, Simon Gregory, Tim Hubbard, James C. Mullikin, Zemin Ning, Simon Potter, Steve Searle, Josep F. Abril, Roderic Guig, Gens Parra, Pankaj Agarwal, Deanna M. Church, Wratko Hlavina, Donna R. Maglott, Victor Sapojnikov, Marina Alexandersson, Lior Pachter, Stylianos E. Antonarakis, Emmanouil T. Dermitzakis, Alexandre Reymond, Catherine Ucla, Robert Baertsch, Mark Diekhans, Terrence S. Furey, Angela Hinrichs, Fan Hsu, Donna Karolchik, W. James Kent, Krishna M. Roskin, Matthias S. Schwartz, Charles Sugnet, Ryan J. Weber, Peer Bork, Ivica Letunic, Mikita Suyama, David Torrents, Evgeny M. Zdobnov, Nicolas Bray, Olivier Couronne, Inna Dubchak, Alex Poliakov, Michael R. Brent, Paul Flicek, Evan Keibler, Ian Korf, Carol Bult, Wayne N. Frankel, Simon Cawley, David Kulp, Raymond Wheeler, Francesca Chiaromonte, Francis S. Collins, Adam Felsenfeld, Richard R. Copley, Richard Mott, Colin Dewey, Nicholas J. Dickens, Richard D. Emes, Leo Goodstadt, Chris P. Ponting, Eitan Winter, Sean R. Eddy, Laura Elnitski, Diana L. Kolbe, Pallavi Eswara, Webb Miller, Scott Schwartz, Gustavo Glusman, Arian Smit, Eric D. Green, Ross C. Hardison, David Haussler, Jia Li, Ming Li, Bin Ma, Pavel Pevzner, Glenn Tesler, Jrg Schultz, John Tromp, Kim C. Worley, Eric S. Lander, Josep F. Abril, Pankaj Agarwal, Marina Alexandersson, Stylianos E. Antonarakis, Robert Baertsch, Eric Berry, Ewan Birney, Peer Bork, Nicolas Bray, Michael R. Brent, Daniel G. Brown, Jonathan Butler, Carol Bult, Francesca Chiaromonte, Asif T. Chinwalla, Deanna M. Church, Michele Clamp, Francis S. Collins, Richard R. Copley, Olivier Couronne, Simon Cawley, James Cuff, Val Curwen, Tim Cutts, Mark Daly, Emmanouil T. Dermitzakis, Colin Dewey, Nicholas J. Dickens, Mark Diekhans, Inna Dubchak, Sean R. Eddy, Laura Elnitski, Richard D. Emes, Pallavi Eswara, Eduardo Eyras, Adam Felsenfeld, Paul Flicek, Wayne N. Frankel, Lucinda A. Fulton, Terrence S. Furey, Sante Gnerre, Gustavo Glusman, Nick Goldman, Leo Goodstadt, Eric D. Green, Simon Gregory, Roderic Guig, Ross C. Hardison, David Haussler, LaDeana W. Hillier, Angela Hinrichs, Wratko Hlavina, Fan Hsu, Tim Hubbard, David B. Jaffe, Michael Kamal, Donna Karolchik, Elinor K. Karlsson, Arkadiusz Kasprzyk, Evan Keibler, W. James Kent, Andrew Kirby, Diana L. Kolbe, Ian Korf, Edward J. Kulbokas, David Kulp, Eric S. Lander, Ivica Letunic, Ming Li, Kerstin Lindblad-Toh, Bin Ma, Donna R. Maglott, Evan Mauceli, Jill P. Mesirov, Webb Miller, Richard Mott, James C. Mullikin, Zemin Ning, Lior Pachter, Gens Parra, Pavel Pevzner, Alex Poliakov, Chris P. Ponting, Simon Potter, Alexandre Reymond, Krishna M. Roskin, Victor Sapojnikov, Jrg Schultz, Matthias S. Schwartz, Scott Schwartz, Steve Searle, Jonathan B. Extensive background information about many of the topics discussed below is provided there. 11, 16771685 (2001), Hardies, S. C. et al. Availability of the genome sequence now makes the determination of the precise integration site in an interesting mutant an almost trivial exercise. UCSC Tech Report UCSC-CRL-02-30, School of Engineering, Univ. 246, 401417 (1995), Adey, N. B. et al. No class II ERVs are known to predate the humanmouse speciation. J. Mol. Natl Acad. Cyp26b1 MGI Mouse Gene Detail - MGI:2176159 - Mouse Genome Informatics Don't read it before a birthday party or any other celebration. (PDF) A Comparative Analysis of a Mouse and Touchpad Based on Genomics 13, 10951107 (1992), Gardiner-Garden, M. & Frommer, M. CpG islands in vertebrate genomes. Nature Genet. The nature and extent of conservation of synteny differs substantially among chromosomes (Fig. 10, 967981 (2000), Kruglyak, S., Durrett, R. T., Schug, M. D. & Aquadro, C. F. Equilibrium distributions of microsatellite repeat length resulting from a balance between slippage events and point mutations. J. Biol. When local (G+C) content is measured in 20-kb windows across the genome, the human genome has about 1.4% of the windows with (G+C) content >56% and 1.3% with (G+C) content <33%. This is known as a feminine rhyme and is reminiscent of nursery songs. Comparative analysis tries to understand the study and . Understanding which aspects are similar will allow scientists to identify when mice can best serve as a useful model organism. Biochim. Although small, single-exon genes may add further to the count, the total seems unlikely to greatly exceed 30,000. Nature Rev. Rev. . J. Mol. We used the genome-wide alignments to examine the extent of conservation in gene-related features, including coding regions, introns, untranslated regions, upstream regions and CpG islands. These include new paralogues for genes responsible for at least five diseases: RFX5, responsible for a type of severe combined immunodeficiency resulting from lack of expression of human leukocyte antigen (HLA) antigens on certain haematopoietic cells152; bestrophin, responsible for a form of muscular degeneration153; otoferlin, responsible for a non-syndromic prelingual deafness154; Crumbs1, mutated in two inherited eye disorders155,156; and adiponectin, a deficiency of which leads to diet-induced insulin resistance in mice157. Hierarchical shotgun sequencing overcomes such difficulties by using local assembly, thus decreasing the number of repeat copies in each assembly and allowing comparison of large regions of overlaps between clones. 9, 10211032 (1995), Sun, H., Tsunenari, T., Yau, K. W. & Nathans, J. Press, Oxford, 1989), Mouse Genome Sequencing Consortium Progress in sequencing the mouse genome. Evaluating the differences and similarities in your data is one of the most straightforward analyses you can ever conduct. Nucleic Acids Res. Science 286, 458462, 479481 (1999), CAS 24), this does not preclude the use of this measure to identify candidate regulatory elements. J. Theor. The former proportion is similar to the 70.1% of human amino acids that are conserved in mouse orthologues, indicating that most of such coding-region SNPs are not under strong selective constraint. The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. 3, 4352 (2002), Cormier, R. T. et al. 101, 20422053 (1998), Saitou, N. & Nei, M. The neighbour-joining method: a new method for reconstructing phylogenetic trees. Beyond this overall tendency, there are specific differences in each of the four repeat classes. We detected 558,000 highly conserved, reciprocally unique landmarks within the mouse and human genomes, which can be joined into conserved syntenic segments and blocks (defined in text). We acknowledge A. Holden for coordinating the Mouse Sequencing Consortium. Morphogenesis of the mammalian blastocyst. PMC Would you like email updates of new search results? By additional sequencing in other mouse strains, we have identified about 80,000 single nucleotide polymorphisms (SNPs). J. Androl. 24 and Table 16) was considerably lower than in coding regions, but much higher than the neutral rate in ancestral repeats or than the average rate across the genome. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in They sometimes contain all exons, but often have suffered deletions and rearrangements that may make it difficult to recognize their precise parentage. In contrast, only 90 out of 8,896 orthologous introns (1%) have identical length, although there is strong correlation between the lengths of orthologous introns. These include mutations in the cystic fibrosis transmembrane conductance regulator gene and the -synuclein gene, which is associated with a familial form of Parkinson's disease191. The speaker will never miss that which goes missing. In many respects, the current paper is a companion to the recent paper on the human genome sequence1. We then set out to investigate the fraction of a mammalian genome under evolutionary selection for biological function. Genome Res. To avoid complications from the tendency of some repeats, such as Alus, to be selectively removed from some regions of the genome1, we used one family of repeats, the LTRs, to monitor the relative frequency of insertion and retention. Importantly, it does not definitively assign an individual conserved sequence as being neutral or selected. a, Estimates are made from the REV model using all aligned sites of the given type in the chromosome. Aug 2015 - Aug 20205 years 1 month. Many abrupt shifts in (G+C) content and repeat density are clearly associated with syntenic breaks, which are therefore more likely to be breaks associated with the rodent lineage45. Transitioning from Soil to Host: Comparative Transcriptome Analysis Chapter 5 begins with Lennie stroking his dead puppy (PETA pickets the farm in chapter 7 (just kidding--there is no chapter 7)). Lennie enters the bunkhouse secretly carrying his new puppy. 12). Together, these estimates suggest that the mammalian gene count may fall at the lower end of (or perhaps below) our previous prediction of 30,00040,000 based on the human draft sequence1. Science 291, 13041351 (2001), ADS Funding was provided by the National Institutes of Health (National Human Genome Research Institute, National Cancer Institute, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of General Medical Sciences, National Eye Institute, National Institute of Environmental Health Sciences, National Institute of Aging, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute on Deafness and Other Communication Disorders, National Institute of Mental Health, National Institute on Drug Abuse, National Center for Research Resources, the National Heart Lung and Blood Institute and The Fogarty International Center); the Wellcome Trust; the Howard Hughes Medical Institute; the United States Department of Energy; the National Science Foundation; the Medical Research Council; NSERC; BMBF (German Ministry for Research and Education); the European Molecular Biology Laboratory; Plan Nacional de I + D and Instituto Carlos III; Swiss National Science Foundation, NCCR Frontiers in Genetics, the Swiss Cancer League and the Childcare and J. Reprod. The individual sequence reads together were found to contain 493-fold coverage of the Sp100-rs gene, suggesting that there are roughly 60 copies in the B6 genome (corresponding to a region of about 6Mb). Very elated to share My Recent Article on "A Comparative Analysis of Hyperparameter Tuned Stochastic Short Term Load Forecasting for Power System Operator " in These could not be explained by strain differences, as similar results were seen with finished sequence from the B6 and 129 strains. CpG islands show a conservation level similar to those of promoter and UTR regions (Fig. A comparative methylome analysis reveals conservation and divergence of dna methylation patterns and functions in vertebrates
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