title: Recent Evolution in Rattus norvegicus Is Shaped by Declining Effective Population Size.
abstract: The brown rat, Rattus norvegicus, is both a notorious pest and a frequently used model in biomedical research. By analyzing genome sequences of 12 wild-caught brown rats from their presumed ancestral range in NE China, along with the sequence of a black rat, Rattus rattus, we investigate the selective and demographic forces shaping variation in the genome. We estimate that the recent effective population size (Ne) of this species = [Formula: see text], based on silent site diversity. We compare patterns of diversity in these genomes with patterns in multiple genome sequences of the house mouse (Mus musculus castaneus), which has a much larger Ne. This reveals an important role for variation in the strength of genetic drift in mammalian genome evolution. By a Pairwise Sequentially Markovian Coalescent analysis of demographic history, we infer that there has been a recent population size bottleneck in wild rats, which we date to approximately 20,000 years ago. Consistent with this, wild rat populations have experienced an increased flux of mildly deleterious mutations, which segregate at higher frequencies in protein-coding genes and conserved noncoding elements. This leads to negative estimates of the rate of adaptive evolution (α) in proteins and conserved noncoding elements, a result which we discuss in relation to the strongly positive estimates observed in wild house mice. As a consequence of the population bottleneck, wild rats also show a markedly slower decay of linkage disequilibrium with physical distance than wild house mice.
authors.affiliation: Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Eva E
authors.initials: EE
authors.lastname: Deinum
authors.affiliation: Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Halligan
authors.affiliation: Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Rob W
authors.initials: RW
authors.lastname: Ness
authors.affiliation: State Key Laboratory of Integrated Management of Pest Insects and Rodents in Agriculture, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yao-Hua
authors.initials: YH
authors.lastname: Zhang
authors.affiliation: Institute of Plant Protection, Heilongjiang Academy of Agricultural Sciences, Harbin, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cong
authors.affiliation: State Key Laboratory of Integrated Management of Pest Insects and Rodents in Agriculture, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jian-Xu
authors.initials: JX
authors.lastname: Zhang
authors.affiliation: Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom peter.keightley@ed.ac.uk.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Keightley
mesh_terms: D000818:Animals; D005075:Biological Evolution; D017124:Conserved Sequence / Q000235:genetics; D021901:DNA, Intergenic / Q000235:genetics; D005091:Exons / Q000235:genetics; D016678:Genome; D015810:Linkage Disequilibrium / Q000235:genetics; D051379:Mice; D009154:Mutation / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011156:Population Density; D051381:Rats
chemical_list: D021901:DNA, Intergenic
keywords: DFE-α; Illumina whole genome sequencing; Mus musculus castaneus; PSMC; Rattus norvegicus; bottleneck; comparative population genomics; distribution of fitness effects; effective population size; evolutionary adaptation