Viruses containing RNA as their genetic material usually have a great capacity to adapt. This is so because the viral polymerases responsible for replicating the genome have a high error rate and therefore, many genomic variants are created at a high generation rate [1, 2]. This high mutation rate of RNA viruses makes them excellent models for addressing evolutionary processes such as epidemic invasions, since their ecological and evolutionary dynamics occur at similar time scales [3–5].
RNA viruses are the causal agents of many emerging diseases and consequently the appearance, or reappearance of diseases caused by these viruses is not infrequent . However, other ecological, social, health or behavioural factors besides their high rate of genetic variation can play an important role in the emergence of a disease .
Rabbit haemorrhagic disease (RHD) is a recent disease that was detected for the first time in 1984 in China, and attributed to rabbits (Oryctolagus cuniculus) imported from the former German Democratic Republic. The disease was described to cause sudden death without apparent deterioration of the rabbit's body condition, although haemorrhaging in the lungs was a frequent observation [7, 8]. Hereafter, the disease rapidly spread to other Asian  and European  countries. The first report of RHD in Europe was in Italy in 1986 , and already in 1988 it was detected in wild rabbits in Spain  and in domestic rabbits in Russia, the Middle East, Africa, America and India .
The aetiological agent of RHD is a single stranded positive sense RNA virus belonging to the family Caliciviridae [13, 14]. Since its discovery, many research efforts have been devoted to its study. However many issues remain unclear or controversial, such as its evolutionary origin or the causes of the rapid succession of epidemics in such a short period of time [15, 16].
Several hypotheses have been proposed to explain the origins of rabbit haemorrhagic disease virus (RHDV), for example: (i) spread of brown hare syndrome virus - a closely related calicivirus - to the rabbit , (ii) changes in the properties of a non pathogenic virus that make it virulent; or (iii) the virus arose from a virus infecting another species . The detection of RHDV specific antibodies and RNA fragments in rabbit serum samples from 1955 to 1980 [19–21], however, seem to support the idea that the virus was already circulating in Europe in an avirulent form before the first epidemic was detected in China in 1984 .
Several causes have also been proposed to explain the rapid expansion of RHD. Initially it was assumed that China was the origin from where the virus spread causing severe epidemics [18, 22]. However, subsequent phylogenetic studies have demonstrated that the Chinese strains of the virus originated in Europe and currently circulating RHDV strains do not have a single origin. Rather, the virus seems to have originated at least twice in the past: firstly in Europe, without causing the disease, and later in the rabbits exported to China [16, 23].
These studies have also detected a large number of RHDV evolutionary lineages that show low genetic divergence both within and among phylogenetic groups [17, 19, 24, 25]. Some of these lineages do not present a clear geographic structure, but they do reflect a temporal structure whereby some lineages become extinct or less frequent, while others derived from them are able to persist and cause new outbreaks of the disease [16, 17, 24]. Despite showing no significant genetic differences in different geographic regions, RHDV does differ in its epidemiology and virulence [15, 26–29].
Some regions, notwithstanding the drastic reductions suffered by rabbit populations after a first epidemic, have seen a decline in the initially high virulence of RHDV and this has enabled populations to gradually recover [15, 26]. In the Iberian Peninsula, however, where rabbits are of great ecological and economic significance [30, 31], RHD still affects many regions in which rabbit populations have been decimated or even extinguished [28, 32].
This heterogeneity in the way RHDV affects rabbits in different geographic regions may indicate that there are factors such as the host, climate or population size that determine the epidemiology of the virus [15, 28]. Regarding the host, in the Iberian Peninsula, the European rabbit is an autochthonous species. Analyses of mitochondrial and nuclear markers have revealed two highly divergent lineages in the European rabbit within the Iberian Peninsula that correspond to subspecies O. c. algirus and O. c. cuniculus [33–36]. These two lineages are the result of two divergent populations that evolved separately for a long time in two glacial refugia, one located in the southwest of the Iberian Peninsula and another in the northeast. A post-glacial expansion might have created a contact zone in the center of the Iberian Peninsula . Furthermore, the northern O. c. cuniculus expanded outside of the Iberian Peninsula and originated all European rabbits, as well as those of North Africa, America, Australia, New Zealand and all the domestic breeds. This expansion originated an intense bottleneck effect that diminished considerably the genetic diversity in the O. c. cuniculus populations outside of the Iberian Peninsula [34, 38–40]. Consequently, the rabbit in the Iberian Peninsula shows the largest genetic diversity across the world distribution of the species [34, 41]. This genetic distinctiveness might pose different selective pressures and evolutionary constraints for RHDV compared to other regions. However, so far, comparative studies including the two rabbit lineages are scarce [16, 42].
The objectives of the present study were: to examine the evolutionary history of RHDV in the Iberian Peninsula and to infer the virus' demographic history, with special focus on its Western European distribution. Given the genetic characteristics of this virus, we would expect to observe: (i) a high genetic diversity and (ii) a temporal genetic structure due to its high mutation rate. In terms of the possible origin of the virus and disease in the Iberian Peninsula, we could speculate that (iii) if a virulent form of the RHDV was introduced, the age of the most recent common ancestor should correspond to the time elapsed since the appearance of the disease, while if the virus already existed in an avirulent form, its age will be older. Also, according to the recent and rapid geographic expansion of RHDV we would expect (iv) its demographic history to reflect significant growth of its populations and that (v) if the intensity of the epidemics has decreased, or at least the number of hosts, a subsequent decline should also be observed.