Although the evolution of this genus has been studied by a number of authors, details are still being elucidated. A brief summary of the pattern that has emerged is as follows: The most basal split in the genus is between the reptile/bird species and the mammalian species. The bird/reptile
clade appears to be related to the genera
Haemoproteus,
Leukocytozoon and
Polychromophilus. The genus
Hepatocystis appears to have evolved from with the mammalian species clade. Within the mammalian species the subgenus
Laverinia appears to be basal with the subgenus
Plasmodium and the rodent species being sister clades.
Hepatocystis appears to have diverged after the separation of the rodent species. The species infecting lemurs may belong in the subgenus
Plasmodium instead of their current placement within the subgenus
Vinckeia. Within the subgenus
Plasmodium,
P. vivax groups with an Asian clade which appears to be rooted in Africa.
P. malaria and
P. ovale both belong to an African clade and are more closely related to each other than to
P. vivax. Within the subgenus
Laverinia P. falciparum and
P. reichenowi form a clade while the other four known species form a second clade. There are a number of additional species in these taxa that await full description so changes to the branching order are likely. However the overall arrangement outlined above seems to be supported by a number of studies by different authors and is unlikely to change. Given the recently recognised paraphytic nature of several of the taxa above, the introduction of new genera and possibly families in the near future seems highly likely.
Relations with other Haemosporidian genera While most phylogenetic trees have tended to agree that
Plasmodium has descended from
Leukocytozoon or
Haemoproteus like species a Bayesian phylogenetic reconstruction suggests that
Plasmodium may be the ancestral genus that has given rise to
Haemoproteus and other genera. This grouping is supported by previous results. A study of DNA sequences suggests that the genus is paraphytic with
Hepatocystis being related to the mammalian species and
Polychromophilus being related to the reptile species. This study also supports the ancestor of
Plasmodium being a
Leucocytozoon like species and that
Plasmodium is more closely related to the
Haemoproteus - specifically the subgenus
Parahaemoproteus - than to
Leucocytozoon. A paper by Blanquart and Gascuel examined
Plasmodium 84 mitochondrial sequences and included
Hepatocystis,
Haemoproteus and
Leukocytozoon sequences. The results agree with the previous analyses showing that
Hepatocystis,
Haemoproteus and
Plasmodium appear to be derived from a
Leukocytozoon ancestor.
Hepatocystis appears to be a sister group to the great ape-rodent clade with the lower primate clade being ancestral to all three. In terms of
Plasmodium subgenera they suggest that the subgenus
Plasmodium is ancestral to both
Laverania and
Vinckeia. A study of parasites infecting bats found that the bats were infected by species of the genera
Hepatocystis,
Plasmodium,
Polychomophilus and
Nycteria. 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 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 ) 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 ). Although Poinar has suggested a date of ~, 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. 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 . 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 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 ~. The vectors of
Babesia and
Theileria - ticks - evolved ± . The hard (
Ixodidae) and soft bodied (
Argasidae) ticks diverged ± . 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 ~ (95% credible interval: - ) The dating in this study used a date of for the origin of the genus
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 • • • • • 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. This is consistent with its relationship with the lemur species in the subgenus
Vinckeia.
Other analyses Examination of the protease gene (SERA) in 18 species has shown that the ancestral state had only a single gene and that gene duplications have occurred in the extant species. This paper confirms the groupings found elsewhere with an Asian clade. The rodent species seem to be more closely related to the
Laverania subgenus than does the subgenus
Plasmodium. A deletion mutation of ~100 base pairs including part of the
LS1 rRNA gene is found in the sequences of two African species -
P. gonderi and an undescribed parasite taken from a mandrill - and 2 Asian species -
P. cynomolgi and
P. simiovale. This study did not include mammalian infecting species other than primate and rodent species and for this reason
Laverina may not be as basal as the study suggests. The remaining branching order is consistent with other analyses placing the rodent species as the first branch after the
P. falciparum/
P. reichenowi clade. It places
P. malaria and
P. ovale as being more closely related to each other than to
P. vivax. This is consistent with the proposed Asian origin of
P. vivax. Although bird malaria species use a variety of mosquito vectors from the genera
Aedes,
Anopheles,
Culex,
Culiseta,
Mansonia and
Psorophora, all mammalian species use vectors only from the genus
Anopheles. This
host switch seems to have been associated with a specialization with a particular genus of mosquito. The ability to store
haemozoin appears to have evolved only once in the common ancestor of
Haemoproteus,
Hepatocystis and
Plasmodium. These parasites are restricted to one resident bird fauna over a long evolutionary time span and are not freely spread between the continents with the help of migratory birds. Lineages of the genus
Plasmodium in contrast seem more freely spread between the continents. This suggests that the origin on the genus
Plasmodium may have coincided with the ability to transfer between avian hosts more easily than the other genera. An analysis of a large number of genera This latter paper puts the divergence between the reptile-bird and mammal clades at ± 3.2 million years ago (Mya). Other divergence times reported include •
P. falciparum –
P. reichenowi - (±0.9 million years) •
P. ovale -
P. cynomolgi/
P. gonderi/
P. simiovale/
P. fieldi/
P. inui/
P. fragile/
P. coatneyi/
P. knowlesi - •
P. malariae and
P. inui/
P. hylobati - •
P. malariae/
P. inui/
P. hylobati -
P. chabaudi/
P. yoelii - (±2.6 million years) •
P. knowlesi -
P. cynomolgi/
P. simiovale/
P. fieldi/
P. inui/
P. fragile/
P. coatneyi - (±1.4 million years) An estimate of the dates of evolution of several species Estimates of the mutation rates suggest a date of divergence between
P. falciparum and
P. reichenowi between and . The estimated date of divergence between
P. vivax and
P. knowlesi was between and . This latter period coincides with the radiation of the Old World monkeys which these parasites infect. The date of divergences between
P. berghei,
P. chabaudi and
P. yoelii was estimated to be between and . The main radiation of the rodent family
Muridae occurred ~. A paper based on the analysis of 22 nuclear genes suggests a radiation of malarial parasites within the
Oligocene (34-23 million years ago). The authors also estimated that the mammalian species of this genus evolved and that the order
Haemosporida evolved . While the date of evolution of
P. falciparum is consistent with alternative methods, the other two dates are considerably more recent than other published estimates and probably should be treated with caution. Another paper which examined primate, rodent, lemur, bird and reptile species suggests that the genus originated between and . has proposed that the mammalian
Plasmodium parasites originated over 64 million years ago and that split between
P. falciparum and
P. reichenowi occurred 3.0-5.5 million years ago. These authors suggested that the split between
P. vivax and
P knowlesi occurred - million years ago. This paper also suggested that the genus
Plasmodium evolved between and . Another study has placed the evolution of the subgenus
Laverina between and . The same paper estimated the
P. billbrayi -
P.gaboni split between and and the
P. reichenowi -
P. falciparum between and . Bats evolved between and . Since it appears that the mammalian infecting
Plasmodium species evolved from a bat infecting species, this estimate may provide an upper limit for the date of evolution of these species of
Plasmodium. A larger study suggests that bats evolved . This upper limit for the date of bat infecting parasites is consistent with the estimates of the dates of evolution of the mammalian infecting
Plasmodium species. The divergence of Old World monkeys and apes has been dated to to . Since the subgenus
Laverinia infects apes rather than monkeys, this date suggests an upper limit for the evolution of this subgenus. This date also places an upper limit on the date when the species infecting Old World monkeys evolved. A Bayesian estimate has suggested that the genus
Plasmodium evolved about . An estimate based on the genome sequences of
Plasmodium gallinaceum and
Plasmodium relictum and the previously sequenced mammalian parasite genomes has suggested a divergence date of . This estimate was based on a separation date of 1 million years for the two ovale species. The dates seem to be at odds with other estimates. This may be because the date of separation of the ovale species currently has considerable variance: the 95% confidence interval in one paper was 0.5 – 7.7 Mya.
Laverania Four species (
P. billbrayi,
P. billcollinsi,
P. falciparum and
P. reichenowi) form a clade within the subgenus
Lavernia. This subgenus is more closely related to the other primate species than to the bird species or the included
Leuocytozoon species. Both
P. billbrayi and
P. billcollinsi infect both the chimpanzee subspecies included in this study (
Pan troglodytes troglodytes and
Pan troglodytes schweinfurthii).
P. falciparum infects the
bonobo (
Pan paniscus) and
P. reichenowi infects only one subspecies (
Pan troglodytes troglodytes). Caution has been raised about the adequacy of the description of these new species. A report of a new species that clusters with
P. falciparum and
P. reichenowi in chimpanzees has been published, although to date the species has been identified only from the sequence of its mitochondrion. Further work will be needed to describe this new species, however, it appears to have diverged from the
P. falciparum-
P. reichenowi clade about . A second report has confirmed the existence of this species in chimpanzees. This report has also shown that
P. falciparum is not a uniquely human parasite as had been previously believed. A third report on the epidemiology of
P. falciparum has been published. This study investigated two mitochondrial genes (
cytB and
cox1), one plastid gene (
tufA), and one nuclear gene (
ldh) in 12 chimpanzees and two gorillas from
Cameroon and one lemur from
Madagascar.
Plasmodium falciparum was found in one gorilla and two chimpanzee samples. Two chimpanzee samples tested positive for
Plasmodium ovale and one for
Plasmodium malariae. Additionally one chimpanzee sample showed the presence of
P. reichenowi and another
P. gaboni. A new species -
Plasmodium malagasi - was provisionally identified in the lemur. This species seems likely to belong to the
Vinckeia subgenus but further work is required. A study of ~3000 wild
ape specimens collected from Central Africa has shown that
Plasmodium infection is common and is usually with multiple species. The ape species included in the study were
western gorillas (
Gorilla gorilla), eastern gorillas (
Gorilla beringei), bonobos (
Pan paniscus) and chimpanzees (
Pan troglodytes). 99% of the strains fell into six species within the subgenus
Laverina.
P. falciparum formed a monophyletic lineage within the gorilla parasite radiation suggesting an origin in gorillas rather than chimpanzees. It has been shown that
P. falciparum forms a clade with the species
P. reichenowi. This clade may have originated between and 10000 years ago. It is proposed that the origin of
P. falciparum may have occurred when its precursors developed the ability to bind to sialic acid Neu5Ac possibly via erythrocyte binding protein 175. Humans lost the ability to make the sialic acid Neu5Gc from its precursor Neu5Ac several million years ago and this may have protected them against infection with
P. reichenowi. Another paper has suggested that the
P. falciparum isolates found in apes are derived from humans and that
P. falciparum and
P. reichenowi diverged when humans and chimpanzees/gorillas did (between and ). The origin of
P. falciparum in humans seems likely to have been from bonobos rather than gorillas or chimpanzees. A review of this subgenus has been published Based on the analysis of the cytochrome b gene the relationships in this subgenus appear to as follows:
P. falciparum and
P. reichenowi are sister species. Their closest relation is
P. billcollinsi.
P. gaboni and
P. billbrayi are sister species whose closest relation is
P. gora.
P. gorb is more closely related to the
P. falciparum/
reichenowi/
billcollinsi clade than the
P. gaboni/
billbrayi/
gora clade. This putative taxonomy will need confirmation from other DNA studies. A second study seems to confirm this proposed grouping. The dates of the evolution of the species within the subgenus
Laverania have been estimated as follows: Revised names have been proposed for the
P. gora and
P. gorb species -
Plasmodium blacklocki and
Plasmodium adleri respectively. These names were chosen to honour the malariologists
Saul Adler (1895–1966) and
Donald Blacklock (1879–1953). It has also been proposed that the
P. falciparum strains infecting gorillas should be renamed
Plasmodium praefalciparum. This proposal appears to have been accepted. The species
P. billbrayi seems to be synonymous with earlier named
P. gaboni. Host-parasite relations: •
P. falciparum has been isolated from chimpanzees, gorillas and humans. The non human strains may be reclassified as
P. praefalciparum. •
P. reichenowi has been isolated from chimpanzees. •
P. billcollinsi has been isolated from chimpanzees. •
P. billbrayi has been isolated from chimpanzees. •
P. gaboni has been isolated from chimpanzees. •
P. adleri has been isolated from gorillas. •
P. blacklocki has been isolated from gorillas. •
P. lomamiensis has been isolated from bonobos. •
P. praefalciparum has been isolated from gorillas. Another analysis has proposed the following arrangement of species:
P. billcollinsi,
P. gaboni and
P. reichenowi only infect chimpanzees while
P. adleri,
P. blacklocki and
P. praefalciparum only infect gorillas.
P. praefalciparum appears to be the closest relation to
P. falciparum. A review of the genomes of all the known species in this subgenus found that the divergence between
P. falciparum and
P. praefalciparum occurred between 40,000 and 60,000 years ago. The expansion of
P. falciparum encountered a bottle neck between 4,000 and 6,000 years ago. It appears that
P. falciparum has been introduced into
South America on several occasions. The extant strains fall into two clades - one northern and one southern. The most probable origin of these strains is Africa and it seems that they were introduced with the slave trade. Analysis of 45 single copy nuclear genes from eight species (
P. berghei,
P. chabaudi,
P. falciparum,
P. gallinaceum,
P. knowlesi,
P. reichenowi,
P. vivax,
P. yoelii) using several different phylogenetic methods suggest a divergence data between 294 and 314 between
Theileria and
Plasmodium. genes suggests a sub Saharan origin for
P. falciparum with separate colonisations of Southeast Asia and Oceania. Given the distributions of the other members of
Laverinia it seems likely all the known members of this subgenus originated in Africa. Another species -
Plasmodium lomamiensis - has been described from bonobos. The name is derived from the
Lomami National Park where the parasite was first identified. The relationship of this species to others in the subgenus has yet to be clarified. Another study has shown that the ancestor of
P. falciparum was the gorilla parasite
P. praefalciparum. Asian Old World monkey malaria parasite species infect both colobine and macaque monkeys. The existing divergence between the Asian and African clade of this subgenus seems likely to have been caused by intercontinental
allopatric speciation along with that of their hosts. Malaria parasites of the lemurs are not traditionally grouped with the subgenus
Plasmodium being placed rather within subgenus
Vinckeia. This classification may not be correct. Based on an analysis of the mitochondria, these parasites seem to group with the others infecting primates. The origin of the primate infecting species (excluding those in the
Laverina subgenus) may date back to the
Eocene - a time when the primate radiation began. This analysis also suggests that the species infecting gorillas and humans may have originated in chimps.
Plasmodium: Asian clade At least nine species belong to the 'Asian' clade of
Plasmodium. These species include
Plasmodium coatneyi,
Plasmodium cynomolgi,
Plasmodium fieldi,
Plasmodium fragile,
Plasmodium inui,
Plasmodium hylobati,
Plasmodium simiovale,
Plasmodium simium and
Plasmodium vivax. As a rule (with the noticeable exception of
P. knowesli), the Asian species have a 72-hour intra erythroctytic life cycle. Analysis of the
merozoite surface protein in ten species of the Asian clade suggest that this group diversified between 3 and 6.3 million years ago - a period that coincided with the radiation of the macques within South East Asia. The inferred branching order differs from that found from the analysis of other genes suggesting that this phylogenetic tree may be difficult to resolve. Positive selection on this gene was also found. In an analysis of the SSU rRNA gene it was found that all Asian simian
Plasmodium species have a single S-type-like gene and several A-type-like genes. A 50 residue insertion in the V7 variable region near the stem 43 is shared exclusively by the S-type like sequences of the Asian simian
Plasmodium species and the S- and O-type sequences of
P. vivax. This is consistent with their shared ancestry.
Plasmodium vivax may have originated in
Asia and the related species
Plasmodium simium appears to be derived through a transfer from the human
P. vivax to
New World monkey species in
South America. This was proposed in a study of howler monkeys near
São Paulo,
Brazil. Another paper has suggested an African origin for
P. vivax. Another paper reported the presence of
P. vivax in
gorillas and
chimpanzees. The DNA sequences analysed fell into two clades. One clade included all the
human strains: the second clade seems likely to be an undescribed species. The gorilla and chimpanzee strains did not group by species suggesting that
P. vivax transmission occurs between these species. The authors suggested an Africa origin for
P. vivax. A paper has suggested that
P. vivax has an African origin and underwent a severe bottleneck and then expanded rapidly once it left Africa. An African origin for
P. vivax would explain the presence of
P. gonderi - an Africa species - within this clade.
Plasmodium species have been isolated from
orangutans. This is consistent with an African origin of the Asian clade. A study of worldwide isolates of
P. vivax found the maximum diversity to lie within South East Asia, suggesting this as the origin of this species. The same paper found that isolates in the Americas fell into two groups suggesting that there were at least 2 separate introductions of this parasite into the Americas. ;Time to most recent common ancestor
P. vivax appears to have evolved between 45,000 and 82,000 years ago from a species that infects south east Asian macques. This is consistent with the other evidence of a south eastern origin of this species. A second estimate put the earliest date of the evolution of
P. vivax at 265,000 years. An estimate of the date of origin of
P. vivax has placed it at 768,000 years ago. It may have appeared in
India between 79,235 and 104,008 years ago. A study of
P. vivax in the Americas suggests that the strains in
Venezuela and northeastern
Brazil diverged from the others ~30,000 years ago. This separation may have occurred before the parasite was introduced into South America. The most recent common ancestor of the extant
P. knowlesi strains has been estimated to have appeared 257,000 (95% credibility interval 98,000–478,000) years ago.
P. knowlesi underwent a rapid population growth between approximately 30,000 and 40,000 years ago. This era follows the growth in the human population in this area (~50,000 years ago). ;Branching order
P. coatneyi and
P. inui appear to be closely related to
P. vivax. Also
P. vivax and
P. cynomolgi appear to be related. The pattern emerging from this data suggests that the ancestor of
P. gonderi and the 'Asian' clade (
P. coatneyi,
P. cynomolgi,
P. fieldi,
P. fragile,
P. hylobati,
P. inui,
P. knowlesi,
P. simiovale and
P. vivax) infected a primate host - perhaps the ancestor of the extant
rhesus monkey - and migrated with its vertebrate host from Africa to Asia via the Middle East. The Asian branch then gave rise to several clades -
P. fragile-
P. coatneyi/
P. knowlesi,
P. hylobati/
P. inui and
P. cynomolgi -
P. simium/
P. vivax.
P. fieldi,
P. simiovale and
P. vivax appear to be relatively early diverging species within this clade. This mutation was not found in the other species of this group that were examined -
P. fragile,
P. knowelsi,
P. simiae and
P. vivax. These mutations are rare and suggest a relationship between the first three species to the exclusion of the others. ;Host relations
P. cynomolgi,
P. inui and
P. knowlesi infect primates of the genus
Presbytis.
P. cynomolgi,
P. fieldi,
P. inui,
P. knowlesi and
P. semiovale infect primates of the genus
Macaca.
P. georgesi and
P. gondori infect primates of the genus
Cocerebus.
P. gondori infects primates of the genus
Mandillus. ;Additional species Within the 'Asian' clade are three unnamed potential species. One infects each of the two chimpanzee subspecies included in the study (
Pan troglodytes troglodytes and
Pan troglodytes schweinfurthii). These two species can only be distinguished by genetic means and they separated between and . A second estimate has placed the separation of these species at (95% confidence interval 0.7-7.7 Mya) One paper has reported a strain of malaria in a chimpanzee with a mitochondrial sequence identical to that of
P. ovale and a second closely related to it. It seems likely as has been proposed earlier that
P. ovale may have an animal reservoir. Two unnamed potential species infect the bonobo (
Pan paniscus) and these are related to the
P. malariae/
P. brazillium clade. The species
P. gonderi appears to be the closest relation to the Asian clade.
Plasmodium malariae Plasmodium malariae has been considered to be closely related to
Plasmodium brasilianum and
Plasmodium rhodiani. These species may be a single species with multiple hosts. Because the number of strains that have examined to date remains small, retirement of the
brasilianum and
rhodiani species names to junior synonym status should probably be delayed.
Rodent species Although the branching order among the mammalian clades has not yet been determined the branching order in the rodent infections species has been studied. The rodent parasites (
P. berghei,
P. chabaudi,
P. vinckei and
P. yoelii) seem to form a distinct clade.
P. berghei and
P. yoelii appear to be sister species as do
P. chabaudi and
P. vinckei. The separation dates between
P. berghei and
P. yoelii has been estimated to be (95% credibility interval 2.5 - 6.0); that between
P. chabaudi and
P. vinckei has been estimated to be (95% credibility interval 5.5 - 12.6); and that between the
P. berghei/
P. yoelii and
P. chabaudi/
P. vinckei clades to be (95% credibility interval 9.0 - 17.5). These estimates are consistent with those from another paper that included a number of primate infecting species.
Notes A recently (2009) described species (
Plasmodium hydrochaeri) that infects capybaras (
Hydrochaeris hydrochaeris) may complicate the phylogentics of this genus. This species appears to be most similar to
Plasmodium mexicanum a lizard parasite. Further work in this area seems indicated. Unlike other eukaryotes studied to date
Plasmodium species have two or three distinct SSU rRNA (18S rRNA) molecules encoded within the genome. suggesting that the classification of species into the subgenus
Plasmodium may have an evolutionary and biological basis. It is known from many written historical sources that
P. vivax malaria was endemic in the wetlands of
England from the 1500s until the 20th century. It is suspected that this disease was introduced by the
Romans sometime before 400 AD. It seems likely that it remained endemic in these areas at least up to 1000 AD. A study in
Senegal of 25 strains isolated there suggests that
P. falciparum underwent a major (60-fold) population expansion of ~20,000-40,000 years ago. A population study based on isolates from several countries suggests that distinct clustering of continental populations - Africa, Southeast Asia and Oceania - has occurred. Within these grouping there has been some further clustering - West Africa versus East Africa, Thailand versus Cambodia. No distinction was identified between isolates from
Mali and
Burkina Faso. ==Host range==