Leishmania infantum is the causative agent of zoonotic visceral leishmaniasis (ZVL) in
the Mediterranean region, with the domestic dog as the main reservoir host.
Phlebotomus (Larroussius) ariasi is the principal vector in cooler, forested ecotopes in
southwest Europe, which suggests that it might be subject to environmental and
geographical isolation. However, the population genetics of P. ariasi had been little
studied before this thesis, which investigated how the population differentiation of this
vector might affect its ability to spread northwards, or persist in the Mediterranean
region, in response to climate and habitat change. Thirty-six spatio-temporal
populations of P. ariasi were molecularly characterized across its range, predominantly
from southwest France but including geographical outgroups from Spain, Portugal and
North Africa. Phylogenetic and population genetic assessments were made based on
five DNA sequences: mitochondrial cytochrome b, nuclear elongation factor-la and
apyrase, plus two anonymous nuclear loci, AAm20 and AAm24. The results
demonstrated the absence of cryptic sibling species of P. ariasi and the selective
neutrality of each locus. Mitochondrial DNA revealed a historical phylogeographic
structure, which was consistent with Pleistocene climate change driving multiple
haplogroup divergences within glacial refuges and phalanx-like population expansions
in interglacial periods. Nuclear loci mostly showed isolation by distance, but some
supported restricted gene flow between the Pyrenees and the Massif Central, France, as
indicated by cytochrome b. A glacial refuge may have existed north of the Pyrenees.
The genetic diversity observed in the northeast Pyrenees, France, permitted an
assessment of the effects of broadleaf forest fragmentation on the differentiation of P.
ariasi. No conclusive evidence was found to support contemporary genetic substructuring
or impoverishment associated with a recent increase in forest fragmentation.
The salivary peptide apyrase revealed a geographical pattern of polymorphism
consistent with the other selectively neutral loci. A range of selection tests indicated that
apyrase was not evolving under positive directional or balancing selection and,
therefore, a genetic arms race with the mammalian host and/or Leishmania parasite was
not supported. The approach taken provides a proof of principle for helping to assess
apyrase and other salivary peptides as vaccine candidates against leishmaniasis
