title: Sequencing the nuclear genome of the extinct woolly mammoth.
abstract: In 1994, two independent groups extracted DNA from several Pleistocene epoch mammoths and noted differences among individual specimens. Subsequently, DNA sequences have been published for a number of extinct species. However, such ancient DNA is often fragmented and damaged, and studies to date have typically focused on short mitochondrial sequences, never yielding more than a fraction of a per cent of any nuclear genome. Here we describe 4.17 billion bases (Gb) of sequence from several mammoth specimens, 3.3 billion (80%) of which are from the woolly mammoth (Mammuthus primigenius) genome and thus comprise an extensive set of genome-wide sequence from an extinct species. Our data support earlier reports that elephantid genomes exceed 4 Gb. The estimated divergence rate between mammoth and African elephant is half of that between human and chimpanzee. The observed number of nucleotide differences between two particular mammoths was approximately one-eighth of that between one of them and the African elephant, corresponding to a separation between the mammoths of 1.5-2.0 Myr. The estimated probability that orthologous elephant and mammoth amino acids differ is 0.002, corresponding to about one residue per protein. Differences were discovered between mammoth and African elephant in amino-acid positions that are otherwise invariant over several billion years of combined mammalian evolution. This study shows that nuclear genome sequencing of extinct species can reveal population differences not evident from the fossil record, and perhaps even discover genetic factors that affect extinction.
authors.affiliation: Pennsylvania State University, Center for Comparative Genomics and Bioinformatics, 310 Wartik Building, University Park, Pennsylvania 16802, USA. webb@bx.psu.edu
authors.forename: Webb
authors.initials: W
authors.lastname: Miller
authors.forename: Daniela I
authors.initials: DI
authors.lastname: Drautz
authors.forename: Aakrosh
authors.initials: A
authors.lastname: Ratan
authors.forename: Barbara
authors.initials: B
authors.lastname: Pusey
authors.forename: Ji
authors.initials: J
authors.lastname: Qi
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Lesk
authors.forename: Lynn P
authors.initials: LP
authors.lastname: Tomsho
authors.forename: Michael D
authors.initials: MD
authors.lastname: Packard
authors.forename: Fangqing
authors.initials: F
authors.lastname: Zhao
authors.forename: Andrei
authors.initials: A
authors.lastname: Sher
authors.forename: Alexei
authors.initials: A
authors.lastname: Tikhonov
authors.forename: Brian
authors.initials: B
authors.lastname: Raney
authors.forename: Nick
authors.initials: N
authors.lastname: Patterson
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lindblad-Toh
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: James R
authors.initials: JR
authors.lastname: Knight
authors.forename: Gerard P
authors.initials: GP
authors.lastname: Irzyk
authors.forename: Karin M
authors.initials: KM
authors.lastname: Fredrikson
authors.forename: Timothy T
authors.initials: TT
authors.lastname: Harkins
authors.forename: Sharon
authors.initials: S
authors.lastname: Sheridan
authors.forename: Tom
authors.initials: T
authors.lastname: Pringle
authors.forename: Stephan C
authors.initials: SC
authors.lastname: Schuster
mesh_terms: D000349:Africa; D000818:Animals; D002467:Cell Nucleus / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D004606:Elephants / Q000033:anatomy & histology / Q000235:genetics*; D019143:Evolution, Molecular; D053476:Extinction, Biological; D005260:Female; D005580:Fossils; D016678:Genome / Q000235:genetics*; D023281:Genomics; D006197:Hair / Q000378:metabolism; D006801:Humans; D007194:India; D008297:Male; D010802:Phylogeny; D017422:Sequence Analysis, DNA / Q000379:methods*