established genus plasmodium. the authors suggested that the origin of the plasmodium/hepatocystis clade was likely to have been in africa. within this genus the first to diverge were the avian and reptile species. the next clade to diverge was that of the polychomophilus species. this was followed in branching order by the nycteria species. the subgenus laverinia was the next to diverge followed by the subgenus vinckeia. the crown of the tree was formed by the subgenus plasmodium and the genus hepatocytis. this tree did not support the inclusion of p. ovale in the subgenus vinckeia but agreed with previous analyses suggesting that p. malaria is more closely related to the asian clade than p. ovale is. several of the bat infecting plasmodium species appear to be related to the rodent species. bats appear to have evolved ~66 million years ago in africa which - assuming that the phylogenetic tree in schaer et al is correct - places an upper limit on the date for the evolution of the mammalian species of plasmodium. another study of the genera leucocytozoon, haemoproteus, parahaemoproteus, polychromophilus and plasmodium found that leucocytozoon occupied a basal position and that polychromophilus and plasmodium were sister clades. a study of polychromophilus species found that this genus lies within the avian/reptile clade of plasmodium species. the species infecting the while tail deer - plasmodium odocoilei - was first described in 1967. a study of mitochondrial, plastid and nuclear genes of this species suggests that this species is actually two species that dierged between 2.3 million years ago and 6 million years ago. the phylogenetic tree suggests that the genus nycteria belongs in a clade that contains the lizard and bird species, that polychromophilus form a clade with p. odocoilei and that hepatocystis species in bats forms a clade with the primate and rodent species. it also suggests that the closest relation to plasmodium - other than nycteria, polychromophilus and hepatocystis - is the subgenus parahaemaproteus and that this subgenus is more closed related to plasmodium that to the genus haemoproteus. this study suggests that the subgenus vinkeia is now in need of revision. another paper suggests the transfer of the ancestor of plasmodium from lizards to bats without passage via birds. a study of nycteria suggests that leukocytozoon is basal, followed by heamoproteus. the sister group to plasmodium/nycteria/polychromophilus/hepatocystis is paraheamaproteus. hepatocystis appears to be a derived clade arising from with the subgenus plasmodium. polychromophilius is more closely related to the bird/lizard group than to the mammal infecting species. nycteria is the sister taxon to the genus plasmodium. the genome of haemoproteus tartakovskyi has been sequenced. its genome (23.2 megabases) is similar in size to those of plasmodium. its gc-content is 25.4% which is closer to that of p. falciparum (19.3%) than to p. vivax (42.3%). phylogenetic analyses place it as basal to plasmodium species. its inclusion in a phylogenetic tree suggests that the mammalian species are monophytic. a study of 114 mitochondrial genomes from species belonging to four genera - haemoproteus, hepatocystis, leucocytozoon and plasmodium - has shown that like plasmodium, leucocytozoon and haemoproteus are not monophyletic taxa. the estimated times of the divergence of these genera was after the cretaceous-paleogene boundary (about 66 million years ago) and coincided with the evolution of the extant avian orders. the presence of plasmodium dominicana and the related species vetufebrus ovatus in dominican amber suggests that this genus was present after the cretaceous-paleogene boundary (about 66 million years ago). although poinar has suggested a date of ~35 million years ago, the precise dating of dominican amber is controversial so an exact date for these species cannot currently be safely assigned. another study found that haemoproteus consists of two taxa and that the genus plasmodium is paraphyletic with respect to hepatocystis. the same study also found that plasmodium species of mammals form a well supported clade and this clade was associated with specialization to anopheles mosquito vectors. the plasmodium of birds and squamate reptiles all fall within a single clade with evidence for repeated switching between birds and squamate hosts. one study using bayesian factors to identify the root of the phylogenetic tree has suggested that plasmodium may be basal to haemoproteus, leucocytozoon, paraheamoproteus and polychromophilus. this tree also grouped hepatocystis with plasmodium. rayella is thought to have originated from hepatocystis. a study of the genera hepatocystis, nycteria, plasmodium and polychromophilus found that polychromophilus was basal to the other genera and that plasmodium and hepatocystis were sister clades. another study has shown that parahaemaproteus and haemoproteus appear to be distinct genera the same study also shown that nycteria and hepatocystis lay within the plasmodium clade. plasmodium odocoilei was most closely related to genus polychromophilus. haemocystidium appeared to be the genus most closely related to plasmodium. a clade that infect ungulates has been identified. this clade includes species that infect water buffalo (bubalus bubalis) and goats (capra aegagrus hircus). the species infecting goats has been named plasmodium caprae. this clade includes species that infect north american white-tailed deer (odocoileus virginianus) and african antelopes (cephalophus). this clade appears to be basal to the other species infecting mammals including the genus polychromophilus. possible evolution the evidence suggests the following evolutionary scenario: plasmodium evolved from a leucocystis like ancestor. this ancestor gave rise to the subgenus parahaemoproteus. both of these taxa infect birds. plasmodium evolved from its parahaemoproteus ancestor when it gained the ability to infect lizards. after this plasmodium diverged into a mammal infecting clade and a bird/lizard infecting clade. within the bird/lizard clade some species developed the ability to infect bats (nycteria). within the mammalian clade a number of species have also developed the ability to infect bats (hepatocystis). since haemoproteus evolved after the evolution of birds this would suggest that an upper limit for the evolution of this genus is approximately 66 million years ago. the columbidae - hosts of the haemoproteus species - evolved in south east asia. it is possible that this also was the origin of the genus haemoproteus. this upper limit may be further reduced. the genus leucocytozoon is thought to have evolved in the oligocene. this would place an upper limit of 33.9 million years ago for the evolution of the genus leucocytozoon. this is in agreement with an estimate of the time of the basal radiation of the genus plasmodium. this date of origin lies within the range of other estimates suggesting that it is plausible. this suggestion is supported by other analyses. relations with non haemosporidian genera the piroplasma are usually considered to be the closest relations to the haemosporidians. based on the evolution of their vectors (ticks) they may have evolved ~300 million years ago. the vectors of babesia and theileria - ticks - evolved 350 million years ago ± 23 million years ago. the hard (ixodidae) and soft bodied (argasidae) ticks diverged 290 million years ago± 23 million years ago. the most likely place of origin of the ticks is northern gondwana and most probably within the region that now constitutes eastern africa. a molecular bayesian study of babesia and theileria species along with plasmodium species suggests that babesia and theileria are sister clades and that they diverged from plasmodium ~56.5 million years ago (95% credible interval: 86.9 million years ago - 28.2 million years ago) the dating in this study used a date of 12.5 million years ago for the origin of the genus plasmodium. the authors also estimated that theileria evolved 23.38 million years ago (95% credible interval 11.1 million years ago – 36.7 million years ago) and that babesia evolved 25.7 million years ago (95% credible interval 12.8 million years ago–40.7 million years ago) another analysis suggests that babesia and theileria are more closely related to the adeleid species than to plasmodium. an examination of sequences from babesiidae, cryptosporiidae, eimeriidae, plasmodiidae, sarcocystiidae, theileriidae, a perkinsus species and 2 dinoflagellates suggests that plasmodium and cryptosporidium are sister taxa and that hepatozoon is basal to them. morrison has shown using molecular data that the haemosporidia are nested within the gregarines and that this clade is distinct from the piroplasms. this latter clade is a sister group of the coccidians. examination of the actin genes suggests that plasmodium is more closely related to the coccidians than to the babesia/theileria clade. it also suggests that cryptosporium is basal in the apicomplexa: this latter finding is consistent with other analyses. phylogenetic trees a number of useful phylogenetic trees of this genus have been published: tree of life website american museum of natural history duval, linda; nerrienet, eric; rousset, dominique; sadeuh mba, serge alain; houze, sandrine; fourment, mathieu; le bras, jacques; robert, vincent; ariey, frederic (2009). "chimpanzee malaria parasites related to plasmodium ovale in africa". plos one. 4 (5): e5520. bibcode:2009ploso...4.5520d. doi:10.1371/journal.pone.0005520. pmc 2677663. pmid 19436742. seethamchai, s; putaporntip, c; malaivijitnond, s; cui, l; jongwutiwes, s (2008). "malaria and hepatocystis species in wild macaques, southern thailand". the american journal of tropical medicine and hygiene. 78 (4): 646–53. doi:10.4269/ajtmh.2008.78.646. pmid 18385364. duval, linda; robert, vincent; csorba, gabor; hassanin, alexandre; randrianarivelojosia, milijaona; walston, joe; nhim, thy; goodman, steve m; ariey, frédéric (2007). "multiple host-switching of haemosporidia parasites in bats". malaria journal. 6: 157. doi:10.1186/1475-2875-6-157. pmc 2212651. pmid 18045505. lee, kim-sung; divis, paul c. s; zakaria, siti khatijah; matusop, asmad; julin, roynston a; conway, david j; cox-singh, janet; singh, balbir (2011). "plasmodium knowlesi: reservoir hosts and tracking the emergence in humans and macaques". plos pathogens. 7 (4): e1002015. doi:10.1371/journal.ppat.1002015. pmc 3072369. pmid 21490952. hayakawa, t; culleton, r; otani, h; horii, t; tanabe, k (2008). "big bang in the evolution of extant malaria parasites". molecular biology and evolution. 25 (10): 2233–9. doi:10.1093/molbev/msn171. pmid 18687771. from these trees it is clear that: the trees are consistent with the origin of plasmodium from leukocytozoon the genus hepatocystis is nested within (paraphytic with) the genus plasmodium and appears to lie within the primate-rodent clade the rodent and primate groups are relatively closely related the primate (subgenus plasmodium) and rodent species (subgenus vinckeia) form distinct groups p. falciparum and p. reichenowi (subgenus laverania) branched off early in the evolution of this genus the 'african' (p. malaria and p. ovale) and 'asian' (p.cynomogli, p. semiovale and p. simium) species tend to cluster together into separate clades. p. gonderi - a species isolated in africa - groups with the asian clade. p. vivax clusters with the 'asian' species. the rodent species (p. bergei, p. chabaudi and p. yoelli) form a separate clade. the species infecting humans do not form a single clade. the genus haemoproteus appears to lie within the bird-lizard clade the lizard and bird species are intermingled although plasmodium gallinaceum (subgenus haemamoeba) and plasmodium elongatum (subgenus huffia) appear be related here so few bird species (three) have been included, this tree may not accurately reflect their real relationship. the bird species (p. juxtanucleare, p. gallinaceum and p. relictum) form a clade that is related to the included leukocytozoon and haemoproteus species. while no snake parasites have been included these are likely to group with the lizard-bird division hepatocystis seems to lie within plasmodium and may be related to the primate clade the bird and lizard species are intermixed as previously found. an analysis of the rodent genera (plasmodium berghei, plasmodium chabaudi, plasmodium vinckei and plasmodium yoelii) suggests that these species may actually be species complexes. the separation of p. chabaudi and p. vinckei has been estimated to be between 3 million years ago and 13 million years ago while that of p. berghei and p. yoelii has been placed at 1 million years ago and 6 million years ago. a paper that included five unnamed lemur species suggested that p. ovale is more closely related to the lemur species than to the other primate ones. it also suggested that the lemur/p. ovale clade is a sister clade of the rodent species. while this is consistent with the placement of the lemur and rodent species in the subgenus vinckeia it is inconsistent with the current placement of p. ovale within the subgenus plasmodium. this paper also supports a basal divergence within the mammalian species into the subgenus laverinia and the others. the subgenera plasmodium and vinckeia with the exception of p. ovale appear to be sister clades. analysis of the apicoplast genes auggests that p. ovale is related to the rodent species. this is consistent