ROBINSON-RECHAVI Marc
- Department of Ecology and Evolution, University of Lausanne, Lausanne, Switzerland
- Bioinformatics & Computational Biology, Evo-Devo, Genome Evolution, Molecular Evolution, Phylogenetics / Phylogenomics
- recommender
Recommendation: 1
Reviews: 2
Recommendation: 1
Evolutionary analysis of candidate non-coding elements regulating neurodevelopmental genes in vertebrates
Combining molecular information on chromatin organisation with eQTLs and evolutionary conservation provides strong candidates for the evolution of gene regulation in mammalian brains
Recommended by Marc Robinson-Rechavi based on reviews by Marc Robinson-Rechavi and Charles DankoIn this manuscript [1], Francisco J. Novo proposes candidate non-coding genomic elements regulating neurodevelopmental genes.
What is very nice about this study is the way in which public molecular data, including physical interaction data, is used to leverage recent advances in our understanding to molecular mechanisms of gene regulation in an evolutionary context. More specifically, evolutionarily conserved non coding sequences are combined with enhancers from the FANTOM5 project, DNAse hypersensitive sites, chromatin segmentation, ChIP-seq of transcription factors and of p300, gene expression and eQTLs from GTEx, and physical interactions from several Hi-C datasets. The candidate regulatory regions thus identified are linked to candidate regulated genes, and the author shows their potential implication in brain development.
While the results are focused on a small number of genes, this allows to verify features of these candidates in great detail. This study shows how functional genomics is increasingly allowing us to fulfill the promises of Evo-Devo: understanding the molecular mechanisms of conservation and differences in morphology.
References
[1] Novo, FJ. 2017. Evolutionary analysis of candidate non-coding elements regulating neurodevelopmental genes in vertebrates. bioRxiv, 150482, ver. 4 of Sept 29th, 2017. doi: 10.1101/150482
Reviews: 2
The quiescent X, the replicative Y and the Autosomes
Replication-independent mutations: a universal signature ?
Recommended by Nicolas Galtier based on reviews by Marc Robinson-Rechavi and Robert LanfearMutations are the primary source of genetic variation, and there is an obvious interest in characterizing and understanding the processes by which they appear. One particularly important question is the relative abundance, and nature, of replication-dependent and replication-independent mutations - the former arise as cells replicate due to DNA polymerization errors, whereas the latter are unrelated to the cell cycle. A recent experimental study in fission yeast identified a signature of mutations in quiescent (=non-replicating) cells: the spectrum of such mutations is characterized by an enrichment in insertions and deletions (indels) compared to point mutations, and an enrichment of deletions compared to insertions [2].
What Achaz et al. [1] report here is that the very same signature is detectable in humans. This time the approach is indirect and relies on two key aspects of mammalian reproduction biology: (1) oocytes remain quiescent over most of a female's lifespan, whereas spermatocytes keep dividing after male puberty, and (2) X chromosome, Y chromosome and autosomes spend different amounts of time in a female vs. male context. In agreement with the yeast study, Achaz et al. show that in humans the male-associated Y chromosome, for which quiescence is minimal, has by far the lowest ratios of indels to point mutations and of deletions to insertions, whereas the female-associated X chromosome has the highest. This is true both of variants that are polymorphic among humans and of fixed differences between humans and chimpanzees.
So we appear to be here learning about an important and general aspect of the mutation process. The authors suggest that, to a large extent, chromosomes tend to break in pieces at a rate that is proportional to absolute time - because indels in quiescent stage presumably result from double-strand DNA breaks. A very recent analysis of numerous mother-father-child trios in humans confirms this prediction in demonstrating an effect of maternal age, but not of paternal age, on the recombination rate [3]. This result also has important implications with respect to the interpretation of substitution rate variation among taxa and genomic compartments, particularly mitochondrial vs. nuclear, and their relationship with the generation time and longevity of organisms (e.g. [4]).
References
[1] Achaz, G., Gangloff, S., and Arcangioli, B. (2019). The quiescent X, the replicative Y and the Autosomes. BioRxiv, 351288, ver. 3 peer-reviewed and recommended by PCI Evol Biol. doi: 10.1101/351288
[2] Gangloff, S., Achaz, G., Francesconi, S., Villain, A., Miled, S., Denis, C., and Arcangioli, B. (2017). Quiescence unveils a novel mutational force in fission yeast. eLife, 6:e27469. doi: 10.7554/eLife.27469
[3] Halldorsson, B. V., Palsson, G., Stefansson, O. A., Jonsson, H., Hardarson, M. T., Eggertsson, H. P., … Stefansson, K. (2019). Characterizing mutagenic effects of recombination through a sequence-level genetic map. Science, 363: eaau1043. doi: 10.1126/science.aau1043
[4] Saclier, N., François, C. M., Konecny-Dupré, L., Lartillot, N., Guéguen, L., Duret, L., … Lefébure, T. (2019). Life History Traits Impact the Nuclear Rate of Substitution but Not the Mitochondrial Rate in Isopods. Molecular Biology and Evolution, in press. doi: 10.1093/molbev/msy247
Evolutionary analysis of candidate non-coding elements regulating neurodevelopmental genes in vertebrates
Combining molecular information on chromatin organisation with eQTLs and evolutionary conservation provides strong candidates for the evolution of gene regulation in mammalian brains
Recommended by Marc Robinson-Rechavi based on reviews by Marc Robinson-Rechavi and Charles DankoIn this manuscript [1], Francisco J. Novo proposes candidate non-coding genomic elements regulating neurodevelopmental genes.
What is very nice about this study is the way in which public molecular data, including physical interaction data, is used to leverage recent advances in our understanding to molecular mechanisms of gene regulation in an evolutionary context. More specifically, evolutionarily conserved non coding sequences are combined with enhancers from the FANTOM5 project, DNAse hypersensitive sites, chromatin segmentation, ChIP-seq of transcription factors and of p300, gene expression and eQTLs from GTEx, and physical interactions from several Hi-C datasets. The candidate regulatory regions thus identified are linked to candidate regulated genes, and the author shows their potential implication in brain development.
While the results are focused on a small number of genes, this allows to verify features of these candidates in great detail. This study shows how functional genomics is increasingly allowing us to fulfill the promises of Evo-Devo: understanding the molecular mechanisms of conservation and differences in morphology.
References
[1] Novo, FJ. 2017. Evolutionary analysis of candidate non-coding elements regulating neurodevelopmental genes in vertebrates. bioRxiv, 150482, ver. 4 of Sept 29th, 2017. doi: 10.1101/150482