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Unique mitochondrial DNA in highly inbred feral cattle

DOI:10.1016/j.mito.2012.05.003
Authors:
Gavin Hudson at Newcastle University
Gavin Hudson
Ian J Wilson at Newcastle University
Ian J Wilson
Brendan A I Payne at Newcastle University
Brendan A I Payne
Joanna L Elson at Newcastle University
Joanna L Elson
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The Chillingham herd of wild Northumbrian cattle remains viable despite over 300 years of in-breeding and a near-homozygous nuclear genome. Here we report the complete mitochondrial DNA sequence using ultra-deep next generation sequencing. Random population sampling of ~10% of the extant herd identified a single mtDNA haplotype harbouring a unique bovine variant present in all other higher mammals (m.11789C/Y421H) which may contribute to their survival.
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Short communication
Unique mitochondrial DNA in highly inbred feral cattle
Gavin Hudson
a
, Ian Wilson
a
, Brendan I.A. Payne
a
, Joanna Elson
a
, David C. Samuels
b
,
Mauro Santibanez-Korev
a
, Stephen J.G. Hall
c
, Patrick F. Chinnery
a,
⁎
a
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK
b
Vanderbilt University Medical Centre, Nashville, TN, United States
c
Department of Biological Sciences, University of Lincoln, UK
abstractarticle info
Article history:
Received 2 February 2012
Received in revised form 23 April 2012
Accepted 10 May 2012
Available online 17 May 2012
Keywords:
mtDNA
Mitochondria
Bovine
The Chillingham herd of wild Northumbrian cattle remains viable despite over 300 years of in-breeding and a
near-homozygous nuclear genome. Here we report the complete mitochondrial DNA sequence using ultra-
deep next generation sequencing. Random population sampling of ~ 10% of the extant herd identified a single
mtDNA haplotype harbouring a unique bovine variant present in all other higher mammals (m.11789C/
Y421H) which may contribute to their survival.
© 2012 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
The Chillingham herd of wild cattle (Fig. 1a) has been inbred for over
300 years (67 generations), and has passed through at least one popu-
lation genetic bottleneck (reduction to 5 males and 8 females in
1947). Apparently in consequence, the microsatellite genome is almost
homozygous, and it is argued that the continuing viability of the herd
(which now numbers 97) is due to the loss of deleterious nuclear alleles
since isolation (Visscher et al., 2001). This affords a unique opportunity
to study a mammalian population in the wild, where the mitochondrial
genome is operating against a background of near-uniform nuclear
genes.
Multiplexed next-generation sequencing, at great depth (mean
coverage 2935 fold, SD =2676), of eight randomly selected, distinct,
Chillingham cattle from the extant population of 93, revealed no
inter-sample sequence variation, with all carrying the same twelve
mtDNA variants (m.169G; m.352G; m.2501A; m.2536A; m.2568C;
m.7851C; m.8346T; m.9682C; m.11476A; m.11789C; m.13310C and
16264A), and no detectable evidence of mtDNA heteroplasmy
(>10% (He et al., 2010)). From these eight samples we can estimate
that 100% of the current population has descended from a single
recent female founder (Clopper–Pearson binomial 95% confidence in-
terval=63% to 100%).
Phylogenetic network-analysis of 256 complete mtDNA se-
quences, rooted with Bos grunniens (Yak), indicates that Chillingham
cattle are related to modern cattle, and belong to the T3 sub-
haplogroup (Fig. 1b). Bootstrap values indicate poor tree placement
(51%, 1000 replicates, Supplementary Fig. 1), likely due to the poor
resolution of haplogroup T3, which has a star-like phylogeny
(Achilli et al., 2008). There was evidence of ancient extant bovine
variation (Aurochs, Bos primigenius: m.2536A, m.9682C m.13310C,
and m.16264A), inherited down the Bos taurus maternal lineage, and
two rare variants (m.2568C and m.11476A, 5.8% and 2.9% of modern
taurine mtDNAs) previously seen only in Italian cattle (Bonfiglio
et al., 2010).
The Chillingham herd was stated by Darwin (1868, revised 1905)
to be a “semi-wild, though much degenerated in size” descendant of
the ancestor of domestic cattle, the aurochs Bos primigenius. Aurochs
remains later than 1500 BC are not known in Britain and although
there are reports of “wild cattle” from medieval Britain these were
probably escapes from husbandry, and were not in districts near
Chillingham. The earliest record of the Chillingham herd is dated
1646 and the most likely origin of the herd is by selection from
local husbanded cattle. The idea of a connection with Roman cattle
has also been advanced, but again there is no evidence that the
Romans brought cattle to Britain, nor that Italian cattle were
subsequently imported, so m.2568C and m.11476A are either recur-
rent mutations, or are more widely distributed amongst European
cattle lineages.
Despite sampling ~10% of the extant Chillingham herd, the lack of
heteroplasmy is not surprising, given the rapid shifts observed in a
single maternal lineage of the Holstein cow, leading to fixation within
2 generations (Olivo et al., 1983).
All eight Chillingham cattle harboured three unique mtDNA
substitutions (m.2501A in 16s rRNA; m.8346T, a synonymous variant
in ATP6; and m.11789C, a non-synonymous variant in URF4) not
found in other modern taurine lineages (Supplementary Table 1).
m.7851C is also found in
Bos indicus and the modern Yak, B. grunniens.
Mitochondrion 12 (2012) 438–440
⁎ Corresponding author at: Institute of Genetic Medicine, Central Parkway, Newcastle
upon Tyne, NE1 3BZ, UK. Tel.: +44 191 5101; fax: +44 191 222 8553.
E-mail address: p.f.chinnery@ncl.ac.uk (P.F. Chinnery).
1567-7249/$ – see front matter © 2012 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
doi:10.1016/j.mito.2012.05.003
Contents lists available at SciVerse ScienceDirect
Mitochondrion
journal homepage: www.elsevier.com/locate/mito
Given the phylogenetic relationship between these different species
(Fig. 1b), m.7851C is likely to be a recurrent mutation. This is similar
to other B. taurus breeds, which harbour 5 +/− 1.06 unique mtDNA
variants (Achilli et al., 2008). Based on a phylogenetic mutation rate
of 2.043 ± 0.099 ×10
− 8
/base-pair/year for the mtDNA coding region
(15,247 bp) (Achilli et al., 2008), the herd is predicted to have a
Fig. 1. (a) The Chillingham wild cattle, Bos taurus. (b) Phylogenetic network of 256 complete Bovine mitochondrial DNA sequences based on coding-region variations relative to the
bovine reference sequences (BRS, GenBank accession no. V00654). The relative positions and population frequencies of Chillingham cattle, Asian Auroch (Bos indicus), European
Auroch (Bos primigenius) and Banteng wild cattle (Bos javanicus ) are shown for reference. The network is shown rooted to the Yak (Bos grunniens) and indicates the major taurine
haplogroups (Supplementary Fig. 1). Node sizes are proportional frequency and all variant weights were considered equal.
439G. Hudson et al. / Mitochondrion 12 (2012) 438– 440
common maternal T3 ancestor ~12,000 years ago, in keeping with the
Neolithic domestication of European founder cattle in the Fertile
Crescent.
Inbreeding is generally found to reduce fitness in both farmed and
wild animals (Visscher et al., 2001), so the continued survival of the
isolated Chillingham herd suggests that deleterious alleles have
been purged from the population. It is conceivable that the diver-
gence of the Chillingham mtDNA genome contributes to the herd vi-
ability. This could, in part, be due the presence of m.11789C (Y421H),
which resides in a highly conserved region of the complex I ND4
respiratory chain subunit. The histidine residue found in the
Chillingham cattle is the sole allele in almost all other higher
mammals (including domesticated sheep and horses), but not in
modern bovine lineages (Supplementary Fig. 2), and is in a region
sensitive to pathogenic mtDNA variation in humans (Taylor and
Turnbull, 2005). Thus, m.11789C is likely to have a functional effect.
This could occur directly through complex I activity, or indirectly
though the nuclear genome, given evidence that mtDNA substitution
drives the adaption in nuclear-encoded respiratory chain proteins in
other species (Blier et al., 2001). Whichever is the case, since that
all are healthy, the Chillingham-specific variant could optimize the
aerobic synthesis of adenosine triphosphate, and thus promote herd
viability in the context of an otherwise invariant nuclear genome.
Acknowledgements
PFC is a Wellcome Trust Senior Fellow in Clinical Science
(WT084980/Z/08/Z) and an NIHR Senior Investigator, who is also
supported through the Wellcome Trust Centre for Mitochondrial Re-
search (WT096919Z/11/Z), the Medical Research Council (UK) Trans-
lational Neuromuscular Centre, and the UK NIHR Biomedical Research
Centre for Ageing and Age-related Disease award to the Newcastle
upon Tyne Foundation Hospitals NHS Trust.
Appendix A. Supplementary data
Supplementary data to this article can be found online at http://
dx.doi.org/10.1016/j.mito.2012.05.003.
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Supplementary resource (1)

Supplementary Material 2
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Mitochondrial genomes of extinct aurochs survive in domestic cattle
Article
Archaeological and genetic evidence suggest that modern cattle might result from two domestication events of aurochs (Bos primigenius) in southwest Asia, which gave rise to taurine (Bos taurus) and zebuine (Bos indicus) cattle, respectively [1,2,3]. However, independent domestication in Africa [4,5] and East Asia [6] has also been postulated and ancient DNA data raise the possibility of local introgression from wild aurochs [7,8,9]. Here, we show by sequencing entire mitochondrial genomes from modern cattle that extinct wild aurochsen from Europe occasionally transmitted their mitochondrial DNA (mtDNA) to domesticated taurine breeds. However, the vast majority of mtDNAs belong either to haplogroup I (B. indicus) or T (B. taurus). The sequence divergence within haplogroup T is extremely low (eight-fold less than in the human mtDNA phylogeny [10]), indicating a narrow bottleneck in the recent evolutionary history of B. taurus. MtDNAs of haplotype T fall into subclades whose ages support a single Neolithic domestication event for B. taurus in the Near East, 911 thousand years ago (kya).