title: Evolution of Local Mutation Rate and Its Determinants.
abstract: Mutation rate varies along the human genome, and part of this variation is explainable by measurable local properties of the DNA molecule. Moreover, mutation rates differ between orthologous genomic regions of different species, but the drivers of this change are unclear. Here, we use data on human divergence from chimpanzee, human rare polymorphism, and human de novo mutations to predict the substitution rate at orthologous regions of non-human mammals. We show that the local mutation rates are very similar between human and apes, implying that their variation has a strong underlying cryptic component not explainable by the known genomic features. Mutation rates become progressively less similar in more distant species, and these changes are partially explainable by changes in the local genomic features of orthologous regions, most importantly, in the recombination rate. However, they are much more rapid, implying that the cryptic component underlying the mutation rate is more ephemeral than the known genomic features. These findings shed light on the determinants of mutation rate evolution.
  
  
  
  local mutation rate, molecular evolution, recombination rate.
authors.affiliation: Sector for Molecular Evolution, Institute for Information Transmission Problems of the RAS (Kharkevich Institute), Moscow, Russia.|M. V. Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Nadezhda V
authors.initials: NV
authors.lastname: Terekhanova
authors.affiliation: Sector for Molecular Evolution, Institute for Information Transmission Problems of the RAS (Kharkevich Institute), Moscow, Russia.
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Seplyarskiy
authors.affiliation: Sector for Molecular Evolution, Institute for Information Transmission Problems of the RAS (Kharkevich Institute), Moscow, Russia.|M. V. Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Ruslan A
authors.initials: RA
authors.lastname: Soldatov
authors.affiliation: Sector for Molecular Evolution, Institute for Information Transmission Problems of the RAS (Kharkevich Institute), Moscow, Russia.|M. V. Lomonosov Moscow State University, Moscow, Russia.|Skolkovo Institute of Science and Technology, Skolkovo, Russia.
authors.forename: Georgii A
authors.initials: GA
authors.lastname: Bazykin
mesh_terms: D000818:Animals; D005075:Biological Evolution; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics; D019143:Evolution, Molecular; D015894:Genome, Human / Q000235:genetics; D023281:Genomics / Q000379:methods; D015186:Hominidae / Q000235:genetics; D006801:Humans; D008322:Mammals / Q000235:genetics; D008957:Models, Genetic; D009154:Mutation; D059645:Mutation Rate; D002679:Pan troglodytes / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D004247:DNA