%0 Journal Article %1 doi:10.1093/molbev/msy188 %A Booker, Tom R %A Keightley, Peter D %D 2018 %J Molecular Biology and Evolution %K genomic_landscape linked_selection mouse simulation simulation-based_inference %P msy188 %R 10.1093/molbev/msy188 %T Understanding the factors that shape patterns of nucleotide diversity in the house mouse genome %U http://dx.doi.org/10.1093/molbev/msy188 %X A major goal of population genetics has b een to determine the extent by which selection at linked sites influences patterns of neutral nucleotide di versity in the genome . Multiple lines of evidence suggest that diversity is influenced by both positive and negative selection . For example, in many species there are troughs in diversity surrounding functional genomic elements , consistent with the action of either background selection (BGS) or selective sweeps . In this study, we investigated the causes of the diversity troughs that are observed in the wild house mouse genome . Using the unfolded si te frequency spectrum (uSFS) , we estimated the strength and frequencies of deleterious and advantageous mutations occurring in different func tional elements in the genome. We then used t hese estimates to param eteriz e forward - in - time simulations of chromosomes, using realistic distributions of functional elements and recombination rate variation in order to determine if selection at linked sites can explain the observed patterns of nucleotide diversity. The simu lations suggest that BGS alone cannot explain the dips in diversity around either exons or conserved non - coding elements (CNEs) . A combination of BGS and s elective sweeps produce s deeper dips in diversity than BGS alone , but the inferred parameters of sele ction cannot fully explain the patterns observed in the genome . O ur results provide evidence of sweeps shaping patterns of nucleotide diversity across the mouse genome , and also suggest that infrequent, strongly advantageous mutations play an important rol e in this. The limitations of using the uSFS for inferring the frequency and effects of advantageous mutations are discussed.

@article{doi:10.1093/molbev/msy188, abstract = {A major goal of population genetics has b een to determine the extent by which selection at linked sites influences patterns of neutral nucleotide di versity in the genome . Multiple lines of evidence suggest that diversity is influenced by both positive and negative selection . For example, in many species there are troughs in diversity surrounding functional genomic elements , consistent with the action of either background selection (BGS) or selective sweeps . In this study, we investigated the causes of the diversity troughs that are observed in the wild house mouse genome . Using the unfolded si te frequency spectrum (uSFS) , we estimated the strength and frequencies of deleterious and advantageous mutations occurring in different func tional elements in the genome. We then used t hese estimates to param eteriz e forward - in - time simulations of chromosomes, using realistic distributions of functional elements and recombination rate variation in order to determine if selection at linked sites can explain the observed patterns of nucleotide diversity. The simu lations suggest that BGS alone cannot explain the dips in diversity around either exons or conserved non - coding elements (CNEs) . A combination of BGS and s elective sweeps produce s deeper dips in diversity than BGS alone , but the inferred parameters of sele ction cannot fully explain the patterns observed in the genome . O ur results provide evidence of sweeps shaping patterns of nucleotide diversity across the mouse genome , and also suggest that infrequent, strongly advantageous mutations play an important rol e in this. The limitations of using the uSFS for inferring the frequency and effects of advantageous mutations are discussed.}, added-at = {2018-10-08T21:08:23.000+0200}, author = {Booker, Tom R and Keightley, Peter D}, biburl = {https://www.bibsonomy.org/bibtex/283309e64a9bd7dd2b254a8d6ce817656/peter.ralph}, doi = {10.1093/molbev/msy188}, eprint = {/oup/backfile/content_public/journal/mbe/pap/10.1093_molbev_msy188/2/msy188.pdf}, interhash = {b9c10d39cf9a7ae86de17e7bd333972d}, intrahash = {83309e64a9bd7dd2b254a8d6ce817656}, journal = {Molecular Biology and Evolution}, keywords = {genomic_landscape linked_selection mouse simulation simulation-based_inference}, pages = {msy188}, timestamp = {2018-10-08T21:08:23.000+0200}, title = {Understanding the factors that shape patterns of nucleotide diversity in the house mouse genome}, url = {http://dx.doi.org/10.1093/molbev/msy188}, year = 2018 }