62 R.A. Skuce et al.
5.5.1 EuropeThe European 1 clonal complex, which domi-
nates and is virtually fixed in the UK and Ireland,
is marked by a specific genomic deletion
(RDEu1). It can be inferred that the UK and
Ireland M. bovis population is largely different to
that which dominates the rest of Europe. Euro-
pean 1 also dominates in many other countries
(Canada, USA, Australia, New Zealand, Argen-
tina, Chile, South Africa, etc.), which are former
trading colonies of Britain. There is now genetic
evidence that European 1 most likely originated
in the British Isles and was exported to many
countries worldwide and founded their now
dominant populations (Smith et al., 2011). Bra-
zil is dominated by the European 2 clonal com-
plex, which is also concentrated in Portugal,
reflecting the historical connection between
those countries (Rodriguez-Campos et al.,
2012b).
The fact that European 1 M. bovis has now
been completely eradicated (e.g. in Australia) or
largely eradicated in some countries (e.g. New
Zealand) by test-and-slaughter policies, implies
that European 1 can be eradicated with current
tools, albeit over lengthy time periods. There
seems nothing ‘special’ about European 1 that
should make it impossible to eradicate. Also,
European 1 has been isolated from a wide range
of animal species; this implies that it is no more,
or no less, capable of establishing in wildlife,
depending on whether they are classified as
dead-end or maintenance hosts. It seems plausi-
ble that intensive application of a test-and-
slaughter policy based on tuberculin testing
would have applied a strong selective pressure
on the pathogen population and selected what
might be described as ‘escape mutants’ of the
tuberculin test. Whether European 1 has such a
selective advantage that allowed it to reach high
frequency within the UK and Ireland and beyond
seems unlikely since European 1 was present
before and after the dramatic reduction in bovine
TB due to full implementation of the UK and
Ireland control programmes. It is not clear if
the RDEu1 deletion confers such a fitness advan-
tage, and just because a clonal complex is com-
mon does not necessarily mean that it has a
fitness advantage. However, one potential selec-
tive advantage has been proposed: control over
insertion sequence copy number, which could
impact gene expression and may have allowed
these bacteria to become a globally distributed
and important group (Smith et al., 2011; Smith,
2012).
To investigate the evolutionary history of
M. bovis within the UK and Ireland, rational pop-
ulation samples were typed at a range of infor-
mative mutations. Due to the clonal nature of
modern TB bacteria, where mutations pass to all
progeny, it is possible to propose the evolution-
ary events leading to the dominance of current
clones. It is likely that the UK and Ireland, his-
torically the British Isles, were founded by an
M. bovis that was already deleted at RDEu1,
potentially alongside other lineages that are now
extinct. Regardless of the exact colonization
history, the Eu1 lineage is now predominant in
Britain and Ireland (Allen et al., 2013). The
British and Irish M. bovis populations are
remarkably similar (Allen et al., 2013). As well
as sharing the RDEu1 deletion, they have the
same basic linear phylogeny, providing further
evidence that a single introduction into these
islands occurred, potentially at a time when cat-
tle populations were more homogenized prior to
movement controls. Diversification within each
territory has since occurred, with shared and
region-specific genotypes identified. These
locally evolved variants are useful in attributing
source to imported cases and this facilitates a
crude estimate of the impact of imports from
other regions on outbreak and reactor numbers
in each region.
Surveillance of M. bovis by spoligotyping
and MLVA is an ongoing part of the strategy for
TB control in Britain. Spoligotyping data have
been used to infer the occurrence and clonal
expansion of a common molecular type in
Britain, possibly due to a selective advantage or
invasion of a new ecological niche or host (Smith
et al., 2003). Spoligotyping and MLVA data have
also been used to identify instances of human
M. bovis infection (Gibson et al., 2004; Stone
et al., 2011) and onward transmission to other
humans (Evans et al., 2007). Similarly, MLVA
data have been used to identify incidents of dis-
ease in cattle caused by import from distant
sources (Gopal et al., 2006). The genetic struc-
ture evident in the MLVA, spoligotype and SNP-
based molecular data has led to novel research
hypotheses on diagnostics and vaccines (Smith
et al., 2006a, 2011; Allen et al., 2013) and