The Mammalian Lifestyle Is Energetically Costly
Here are two indisputable facts: we are living in the age of mammals [1], and immunologically
intact mammals are highly resistant to fungal diseases, such that most human systemic
fungal are considered “opportunistic” [2]. Could these two facts be connected? The
mammalian lifestyle is characterized by endothermy, homeothermy, and care for the
young, including nourishment via lactation, all of which are energetically costly
activities. In contrast, reptiles, which are ectotherms, require about one-tenth of
the daily mammalian energy needs [3], and reptilian development is faster and requires
less parental involvement. Given this energy handicap, how did mammals replace reptiles
as the dominant land animals? This essay further develops the hypothesis originally
proposed seven years ago that fungi contributed to the emergence of mammals by creating
a fungal filter at the end of the Cretaceous that selected for the mammalian lifestyle
and against reptiles [4].
Mammals Are Naturally Resistant to Fungal Diseases
Mammals are highly resistant to systemic fungal diseases. Whereas dermatophyte-associated
diseases are common, these are seldom life threatening. For humans most fungal diseases
were described in the 20th century and are associated with changes in the host such
as iatrogenic immunosuppression, antibiotic-mediated disruption of the microflora,
or other immune-impairing conditions as HIV infection, hematologic malignancies, and
rheumatologic conditions. Unlike viral and bacterial diseases human mycoses are seldom
contagious.
Endothermy and homeothermy are thought to contribute to mammalian resistance to mycosis
by creating a thermal exclusionary zone that inhibits most fungal species [5]. The
remarkable resistance of mammals to mycotic diseases is probably a combination of
a vertebrate immune system, with both innate and adaptive arms, and elevated body
temperatures. Experimental evidence for the synergy of temperature and immunity is
apparent from studies of cryptococcal infection in rabbits, which have core temperatures
of 40–41°C [6]. Rabbits are naturally resistant to systemic C. neoformans infection.
However, rabbits can be infected with C. neoformans when inoculated in the skin or
cornea, which are cooler, but the fungus does not disseminate. However, when rabbits
are immunosuppressed with corticosteroids, C. neoformans infection is rapidly fatal
[7].
Primitive mammals like the platypus, with core temperatures near 32°C, are susceptible
to Mucor amphibiorum, a fungus with a maximal thermal tolerance of 36°C that would
make it avirulent for higher mammals [8]. The resistance of mammals to fungal diseases
is in sharp contrast to the vulnerability of other vertebrates, such as amphibians,
a group that is currently under severe pressure from a chrytrid [9]. Like mammals,
amphibians have adaptive immunity, but unlike mammals, they are ectotherms and lack
a thermal environment that is exclusionary to fungi. Hence, their vulnerability to
fungal diseases echoes the experimental findings in rabbits whereby high resistance
is conferred by a combination of high temperature and vertebrate-level immunity [6].
Amphibians can be cured of chrytridomycosis if placed at 37°C [10]. Another example
of the protection provided by the combination of vertebrate-level immunity and endothermy
comes from bats. In the summer bats manifest high activity and mammalian temperatures,
but during winter hibernation their core temperatures drop as they hibernate and become
vulnerable to infection with Geomyces destructans, a fungus that is decimating several
North American bat species [11]. Infected bats woken from hibernation made full recovery
when provided with supportive care, as higher body temperature inhibited fungal growth
[12]. It is noteworthy that birds, which are also endotherms, are susceptible to Aspergillus
fumigatus
[13], a thermotolerant fungus that can survive up to 55°C [14].
A computation of the optimal temperature that would provide maximal protection against
fungi given the caloric needs needed to maintain elevated temperatures yielded a value
of 36.7°C, which is very close to mammalian temperatures [13]. This raises the possibility
that mammalian resistance to fungi through the combination of vertebrate-level immunity
and endothermy could have been the result of selection by pathogenic fungi.
A Fungal Filter at the Cretaceous-Tertiary (K-T) Boundary
Mammals replaced reptiles as the dominant land forms after the catastrophe that marked
the end of the Cretaceous and the beginning of the Tertiary, an event known as the
K-T boundary. The currently favored hypothesis for the demise of dinosaurs and end
of the age of reptiles is a bolide impact approximately 65 million year ago with the
possibility that other events, such as increased volcanism, contributed to disrupting
the cretaceous ecosystem [15]. That ecological calamity was accompanied by massive
deforestation [16], an event followed by a fungal bloom [17], as the earth became
a massive compost. Although one cannot know which spores were present at the time,
the likelihood that pathogenic fungi existed at the K-T boundary is enhanced by the
finding that the potential for pathogenicity probably arose independently several
times in evolution [18].
There is now increasing evidence that large dinosaurs were warm bodied [19], as a
result of their size, which would have entailed considerable heat generation dependent
on food metabolism and their metabolic activities. Large animals at the top of the
food chain, such as dinosaurs, are highly vulnerable to ecosystem disruption. The
altered ecosystem would have implied disruption of food sources and changed climate,
which is thought to have included a significant cooling of the earth [20], by dust
clouds and fires. Such stresses would be expected to weaken any survivors of the bolide
blast with consequent immunological impairment and could have made survivors, and
their eggs, susceptible to fungal diseases, especially if they could not maintain
body warmth in the setting of starvation.
Since there are reptiles today, it is clear that some reptiles survived the K-T boundary
cataclysm. This raises the question, if reptiles were previously so successful, why
did they not reclaim the earth to launch a second reptilian age? It is difficult to
imagine how mammals could have replaced reptiles as the dominant land forms without
some selection mechanism for this energetically costly lifestyle. This led me to propose
the hypothesis that fungal proliferation after the devastation of the KT event preferentially
selected for the fungal-resistant endothermic and hindered the re-emergence of a second
reptilian age [4]. Although we do not know the timeline for the recovery of the planet
climate, it is estimated that photosynthesis was shut down for 6 months and climate
cooling persisted for at least 9 years [20], and the occurrence of a fungal bloom
sufficient to have left fossil evidence implies that surviving animals were exposed
to massive numbers of fungal spores. The darkened skies and cooler temperatures that
accompanied the K-T cataclysm [20] would have shielded the sun and reduced the ability
of ectothermic creatures such as reptiles to induce fevers by insolation, a necessary
activity for protection against fungal diseases. Hence, it is reasonable to posit
that ectothermic creatures unable to induce behavioral fevers and in weakened states
from environmental stress would have been at a severe disadvantage relative to small
mammals with their innate thermal exclusionary zones for fungal growth. Further complicating
the situation for reptiles is that eggs can be vulnerable to fungal attack [21], whereas
mammalian progeny would be protected in placentae.
Climate Change and Future Fungal Threats
Climate warming implies that the temperate gradient from mammals and average environmental
temperatures will be reduced. Higher global temperatures could select for more thermally
tolerant fungi, and it is possible that many fungi with current pathogenic potential
for mammals that are unable to cause disease in mammals due to thermal intolerance
will acquire the capacity to survive at mammalian temperatures and thus become pathogenic
for mammals [22]. This concern is heightened by the fact that some fungi can be easily
adapted to higher temperatures by thermal selection, as exemplified by the generation
of a thermally resistant entopathogenic fungus as an attempt to create a pest control
strain that would be less susceptible to insect-induced behavioral fevers [23].
The Fungal-Mammalian Emergence Hypothesis in Context
The fungal-mammalian emergence hypothesis posits that fungi selected for the emergence
of mammals. The hypothesis suggests an explanation for how the highly energy-intensive
mammalian lifestyle was selected and for the relative resistance of immunologically
intact mammals to fungal diseases. The hypothesis is a plausible synthesis assembled
from very disparate lines of evidence. At this time it is unlikely that experimental
evidence will be available in the near future to validate or refute this hypothesis
simply by the very nature of what it tries to explain, and the remoteness of past
events. For example, given that the animals that died as a result of the KT-related
events represent an extremely small part of the fossil record, it is unrealistic to
imagine finding fossils that could unequivocally be dated to the time in question
with evidence of fungal disease. Fungal diseases can leave traces in the fossil record,
as manifested by the finding of Coccidioides-like spherules in a fossil bison from
the Holocene [24], but those fossils are very recent relative to the KT event and
fungal effects on bone tissue usually reflect chronic infections. In contrast, fungal
diseases caused by microscopic organisms that killed hosts by destroying soft tissues
would leave no fossil record. On the other hand, recent developments with amphibian
chrytridmycosis and the white nose syndrome in bats provide strong circumstantial
evidence for the notion that fungal diseases could have provided strong selection
pressures and driven some species to extinction. Although these are examples of individual
fungal-host interaction in specialized ecological settings, they do provide precedents
for the notion that fungi can be powerful selective forces for vertebrate species.
In addition, there is now considerable evidence that fungi are potential threats to
entire ecosystems [25]. The fungal-mammalian emergence hypothesis will likely continue
to evolve as new information is available and is best considered as a cognitive tool
for stimulating thinking and discussion on global issues related to evolutionary selection,
infectious diseases, and ecological change.