title: The Y-chromosome tree bursts into leaf: 13,000 high-confidence SNPs covering the majority of known clades.
abstract: Many studies of human populations have used the male-specific region of the Y chromosome (MSY) as a marker, but MSY sequence variants have traditionally been subject to ascertainment bias. Also, dating of haplogroups has relied on Y-specific short tandem repeats (STRs), involving problems of mutation rate choice, and possible long-term mutation saturation. Next-generation sequencing can ascertain single nucleotide polymorphisms (SNPs) in an unbiased way, leading to phylogenies in which branch-lengths are proportional to time, and allowing the times-to-most-recent-common-ancestor (TMRCAs) of nodes to be estimated directly. Here we describe the sequencing of 3.7 Mb of MSY in each of 448 human males at a mean coverage of 51×, yielding 13,261 high-confidence SNPs, 65.9% of which are previously unreported. The resulting phylogeny covers the majority of the known clades, provides date estimates of nodes, and constitutes a robust evolutionary framework for analyzing the history of other classes of mutation. Different clades within the tree show subtle but significant differences in branch lengths to the root. We also apply a set of 23 Y-STRs to the same samples, allowing SNP- and STR-based diversity and TMRCA estimates to be systematically compared. Ongoing purifying selection is suggested by our analysis of the phylogenetic distribution of nonsynonymous variants in 15 MSY single-copy genes.
authors.affiliation: Department of Genetics, University of Leicester, Leicester, United Kingdom.
authors.forename: Pille
authors.initials: P
authors.lastname: Hallast
authors.affiliation: Department of Genetics, University of Leicester, Leicester, United Kingdom.
authors.forename: Chiara
authors.initials: C
authors.lastname: Batini
authors.affiliation: Department of Genetics, University of Leicester, Leicester, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zadik
authors.affiliation: Department of Genetics, University of Leicester, Leicester, United Kingdom.
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Maisano Delser
authors.affiliation: Department of Genetics, University of Leicester, Leicester, United Kingdom.
authors.forename: Jon H
authors.initials: JH
authors.lastname: Wetton
authors.affiliation: Laboratory of Forensic and Population Genetics, Department of Toxicology and Health Legislation, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Arroyo-Pardo
authors.affiliation: Molecular and Cellular Therapeutics, The Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Gianpiero L
authors.initials: GL
authors.lastname: Cavalleri
authors.affiliation: Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: de Knijff
authors.affiliation: Istituto Italiano di Antropologia, Rome, Italy Department of Environmental Biology, Sapienza University of Rome, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Destro Bisol
authors.affiliation: Division of Forensic Sciences, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Berit Myhre
authors.initials: BM
authors.lastname: Dupuy
authors.affiliation: Centre of Arctic Medicine, Thule Institute, University of Oulu, Oulu, Finland Utsjoki Health Care Centre, Utsjoki, Finland.
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Eriksen
authors.affiliation: Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City, UT.
authors.forename: Lynn B
authors.initials: LB
authors.lastname: Jorde
authors.affiliation: Department of Genetics, University of Leicester, Leicester, United Kingdom.
authors.forename: Turi E
authors.initials: TE
authors.lastname: King
authors.affiliation: Laboratory of Forensic Genetics and Molecular Archaeology, KU Leuven, Leuven, Belgium Department of Imaging & Pathology, Biomedical Forensic Sciences, KU Leuven, Leuven, Belgium Laboratory of Biodiversity and Evolutionary Genomics, Department of Biology, KU Leuven, Leuven, Belgium.
authors.forename: Maarten H
authors.initials: MH
authors.lastname: Larmuseau
authors.affiliation: Department of Neurosciences, University of the Basque Country, San Sebastián, Spain.
authors.forename: Adolfo
authors.initials: A
authors.lastname: López de Munain
authors.affiliation: Laboratory of Forensic and Population Genetics, Department of Toxicology and Health Legislation, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: López-Parra
authors.affiliation: National Center for Thalassemias, Athens, Greece.
authors.forename: Aphrodite
authors.initials: A
authors.lastname: Loutradis
authors.affiliation: School of Dental Medicine, Institute of Human Genetics, University of Belgrade, Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Milasin
authors.affiliation: Department of Biology, Tor Vergata University, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Novelletto
authors.affiliation: Network of Forensic Science Institutes, Institute of Forensic Medicine, Budapest, Hungary.
authors.forename: Horolma
authors.initials: H
authors.lastname: Pamjav
authors.affiliation: Department of Forensic Medicine, Hjelt Institute, University of Helsinki, Helsinki, Finland Department of Molecular and Medical Genetics, Institute of Applied Genetics, University of North Texas Health Science Center, Fort Worth, Texas.
authors.forename: Antti
authors.initials: A
authors.lastname: Sajantila
authors.affiliation: Institute of Human Genetics, University of Freiburg, Freiburg, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Schempp
authors.affiliation: Department of Genetics, University of Leicester, Leicester, United Kingdom.
authors.forename: Matt
authors.initials: M
authors.lastname: Sears
authors.affiliation: Department of Molecular Biology and Genetics, Boğaziçi University, Istanbul, Turkey.
authors.forename: Aslıhan
authors.initials: A
authors.lastname: Tolun
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Tyler-Smith
authors.affiliation: Laboratory of Socioecology and Social Evolution, Department of Biology, KU Leuven, Leuven, Belgium.
authors.forename: Anneleen
authors.initials: A
authors.lastname: Van Geystelen
authors.affiliation: Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City, UT.
authors.forename: Scott
authors.initials: S
authors.lastname: Watkins
authors.affiliation: Department of Oncology, University of Oxford, Oxford, United Kingdom.
authors.forename: Bruce
authors.initials: B
authors.lastname: Winney
authors.affiliation: Department of Genetics, University of Leicester, Leicester, United Kingdom maj4@le.ac.uk.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jobling
mesh_terms: D041322:Chromosomes, Human, Y / Q000235:genetics*; D019143:Evolution, Molecular; D060148:HapMap Project; D006801:Humans; D008297:Male; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017422:Sequence Analysis, DNA
keywords: Y-STRs; Y-chromosome phylogeny; purifying selection; single nucleotide polymorphisms; targeted resequencing