Discussion
The general result of the simulations suggests that the increase in the
rate of evolutionary novelty emergence, reproductive rate, and propagule
size influence positively the success of colonization of new hosts by a
novel pathogen population (Fig. 2). However, within the scope of the
simulations, the different values of the explored parameters resulted in
distinct impacts on this success. By far, the most significant impact
was observed for the number of propagules; even not adapting to the
selection of the new host, due to the complete absence of emergence of
novelties imposed by the model, an initial population composed of 10
colonizers resulted in a significant increase of the probability to
thrive and persist under suboptimal fitness, even in hosts representing
relatively small compatibility (d0 \(\approx\)1).
Indeed, propagule pressure is extensively known to positively influence
the colonization of new host species (May et al. 2001; Hatcher et al.
2012) - or geographic areas and corresponding communities in the case of
invasive species (Sax et al. 2007; Lockwood et al. 2009; Cassey et al.
2018). Large propagule sizes are usually linked with the reduction of
consequences of demographic (e.g. stochasticity and Allee effects)
(Hufbauer et al. 2013) and genetic (founder’s effect) (Simberloff 2009;
Roman and Darling 2007) processes observed in small population size
during changes in ecologic and geographic distribution. Since every
simulation involving variation in propagule size used a low rate of
emergence of evolutionary novelty and the relative fitness of propagules
were kept unchanged (same d0 despite qualitative
differences in the combination of loci), the advantage conferred by
increasing propagule sizes during colonization appears to be associated
with demographic issues, most likely stochastic, as we did not model
social collaborative processes nor limitation in the encounter of mates
during reproduction (see Hufbauer et al. 2013). However, the rate of
increase in colonization success according to the imposed distance of
the compound phenotype optimum of the new host diminishes with
increasing values of the propagule size, not displaying a direct linear
relationship (Fig. 2c).
Although less evident than the simulations with variable propagule size,
increases in reproductive rate in less than 10 – fold (from 1.5 to 7.5)
resulted in a more expressive increase in the probability of successful
colonization than 1000-fold increases in the rate of emergence of
novelties (from μ =10-6 toμ =10-3). This is an unexpected result,
especially considering that the emergence of new associations - such as
infectious diseases - is often linked by many to high mutation rates of
the consumer associate (Pepin et al. 2008; Selman et al. 2012; Viana et
al. 2015). Hence, our results indicate that the rate of emergence of
evolutionary novelties alone (e.g. mutation rates for simple organisms
such as viruses) has secondary importance in the colonization of new
host species, as suggested in Araujo et al. (2015) and implicitly by the
Stockholm Paradigm (Brooks and Hoberg 2007; Brooks and Boeger 2019;
Brooks et al. 2019; Agosta and Brooks 2020). The accumulation of
accessible historical information - termed the information spaceby Brooks and Agosta (2012) and Agosta and Brooks (2020) - is of greater
importance for the events of host-repertoire expansion (i.e. the
evolutionarily process that precedes what is known as host-switching;
see Braga et al. 2018). It is the accumulation of heritable information
by preceding generations (and ancestors) and its retention in the
biological entities (i.e. populations, species) through time
(=phylogenetic conservatism) that will determine the ability of lineages
to endure ecological and environmental changes or to take advantage of
opportunities (e.g. explore new resources, new habitats). Since
compatibility (i.e. the distance to the actual host optimum) varies
within individuals of a diverse pathogen population, regions of
suboptimal fitness in the ancestral host - albeit potentially at low
frequency in the population - may contain pathogen variants that are
capable of reaching more distant (= more different) resources (new
hosts) than originally higher-fitness variants (see also Araujo et al.
2015; Brooks et al. 2019). Consequently, under this scenario, actual
rates of emergence of new inheritable evolutionary novelties (e.g.
mutations) are less important than the number of individuals colonizing
the new host (=propagule pressure), the rate of reproduction, and the
degree of the variability in the original donor population.
When all three parameters considered are maximized, the simulations
generate pronounced synergism (grey line in Fig. 2). The fact that this
combination of values likely compares to those observed for viruses,
particularly among RNA-viruses (Holmes 2009) is especially significant
in understanding the evolution of this group of organisms and the
corresponding emergence of infectious diseases. This outcome is
compatible with the conclusions of Geoghegan, Duchêne, and Holmes (2017)
that “cross-species transmission is a near universal feature of the
viruses …, with virus-host co-divergence occurring less
frequently…” For instance, continuous oscillations of host species
were suggested as an intrinsically biological feature of coronaviruses
(Menachery et al. 2017), but it is likely a property of viruses in
general and perhaps of pathogenic bacteria as well. It is, thus,
understandable that viruses and bacteria are the most common groups of
organisms associated with emergent infectious diseases (Cleaveland et
al. 2001; Woolhouse and Gaunt 2007; Gubler 2010; Pękala-Safińska 2018;
Duarte-Neto 2019).
Since we expect that in the real-world representatives of the variants
of pathogens are continuously exploring accessible resources (e.g. host
species) (Brooks et al. 2019; Agosta and Brooks 2020) the emergence of
new associations - or colonization of new environments - is expected
when suitable matching (likely imperfect rather than perfect) between
requirements of the pathogen, the resource (i.e. host properties),
and/or environmental conditions meet. Therefore, the original host
species represents an imperfect reference - but, perhaps, the only one
accessible at this time - to describe the relative quality and the
distance of the new resources to the pathogen. Phylogenetic distance
between the host species involved in the host range expansion appears,
within limits, to estimate the multidimensional space of traits that
influence the compatibility of host and a specific pathogen lineage
(Martiny et al. 2013; Braga et al. 2015; Streicker et al. 2010; Gilbert
and Webb 2007). Since the resources defining compatibility vary
according to both host and pathogen species, phylogenetic distances
appear to be the only accessible proxy for the value ofd0 , but it should be considered parsimoniously
because evolutionary convergence of resources (Brooks and McLennan 2002)
and the variability of the pathogen and hosts may influence also the
outcome of the colonization attempts (see for instance Boeger et al.
2005; Araujo et al. 2015).
The results of the present simulations are also fundamental to expand
the understanding of the role of ecological fitting (Janzen 1985b;
Agosta 2006; Agosta and Klemens 2008) on the evolution of ecological
changes. As suggested previously by Araujo et al. (2015), newly
established populations of pathogens may survive for many generations in
a host even in the absence of adaptations. This is a more extreme
scenario of what Darwin called the survival of the adequate (Agosta and
Brooks 2020; Brooks and Agosta 2012). By surviving under these
“suboptimal” conditions, pathogens may expand their temporal window
for the “right” novelty to present itself and allow an increase in the
population’s fitness (adaptation) following the ecological change. For
instance, Antia et al. (2003), modeling a scenario of colonization
similar to the present simulations, suggested that early values of
R0 of a new pathogen may evolve towards an
R0>1 subsequently, under the selective
pressure of the newly colonized host. However, after exploring the
available Sloppy Fitness Space of the pathogen population (Agosta and
Klemens 2008; Agosta et al. 2010; Brooks et al. 2019; Agosta and Brooks
2020), evolutionary novelties emerge randomly in the consumer species
(the pathogen). Thus, the perfect match may never happen (i.e. a
perfectly fit association) despite the influence of selection and the
consumer may remain in a situation of continuous suboptimal fitness
regarding its host species, a scenario analogous to that proposed by Sax
et al. (2007) for invasive species.
Another additional perspective is that the newly established population
of pathogens, although unchanged in its diversity due to the absence or
limited emergence of novelties (phenotypic or genetic), may also expand
the window of opportunity to encounter additional hosts representing
more or simply adequate resources solely by inhabiting a host species
with distinct ecological interactions with the surrounding environment.
For instance, by depicting dissimilar behaviors, the adequate new host
species may increase the probability of the new pathogen population to
encounter other potential hosts not previously available (considering
the ecology of the original host species) through a process that likely
comprises one of the mechanisms of colonization of new hosts species.
This is an empirically recognized process associated with many cases of
emergence of new symbiotic associations - contemporary (Brown 2001) and
historical (Braga et al. 2015) - including one of the possible pathways
of SARS-CoV-2 to humans during the emergence (Ji et al. 2020; Zhang et
al. 2020).
In the case of SARS-CoV-2, the scenario is even more worrisome since
humans became one of the “stones” in the process of host-repertoire
expansion by stepping stones (Braga et al. 2015; Brooks et al. 2019).
COVID19 has rapidly expanded to almost every part of the planet,
providing opportunities for the virus to colonize other human
populations and animal species. Presently, pets – ferrets, cats, and
dogs – and captive wild animals – such as minks, tigers, lions,
macaques, Syrian hamsters, tree shrews, marmosets, and Egyptian fruit
bats (Gryseels et al. 2020; Lin et al. 2020) are known empirically to be
compatible hosts while a much greater range of host species has been
suggested through modeling (Damas et al. 2020) - from old-world monkeys
to anteaters. While many of the presently known compatible host species
are not seriously affected by the virus, they certainly represent unique
selective pressures and opportunities for broader dissemination through
ecological fitting (as suggested above). Hence, we may anticipate
influences connected with the acquisition of new host species on the
genetic make-up of SARS-CoV-2 – among others, it may result in an
increase in its overall genetic variability and/or on the emergence of
unique haplotypes in isolated host populations (as suggested also by
Franklin and Bevins 2020). Indeed, the nature of RNA-viruses replication
influences by host and geographic expansion and isolation are already
known to generate new variants (Franklin and Bevins 2020) with
dissimilar potential virulence to humans. Such evolutionary changes may
result in new strains of the viruses with the ability to generate
diseases with symptomatic, virulence, and epidemiological
characteristics distinct from the original strains (see Jerzak et al.
2007; Bordería, Stapleford, e Vignuzzi 2011). This epidemiological
scenario is complicated by the accumulation of evidence suggesting that
SARS-CoV-2 may take the opposite path (retro-colonizing humans), a
situation already recorded among other coronaviruses for the Siberian
musk deer (Moschus moschiferus) and ferrets (Mustela
lutreola ) (Hadfield et al., 2018; Van Der Hoek et al., 2004). Hence,
despite the recognition that these retro-colonization events are likely
rare (de Morais et al. 2020), they cannot be simply ignored in
epidemiological surveillance systems. The significance of such scenarios
and outcomes is further heightened given the currently expected limited
capacity for viruses to re-infect humans from domestic or synanthropic
wildlife sources. Thus, potential pathways are not under active
surveillance.
The simulations revealed yet another aspect of this host-exploration
dynamics that makes the above-proposed scenario of retro-colonization of
humans particularly important in health surveillance for EIDs. The
simulations strongly suggest that at higher values of the rate of
emergence of evolutionary novelties (e.g. mutation rates for viruses),
the genetic profile of the pathogen - although changing qualitatively
and quantitatively under the selective pressure of the new host resource
- putatively retain “ancestral” variants at low frequency despite
lower supposed fitness (Fig. 4B, C). This outcome provides theoretical
support for the retention of the capacity of fast-evolving lineages to
retro-colonize their previous host species/lineage by ecological fitting
(Janz and Nylin 1998; Janz et al. 2001; Brooks et al. 2019 ). RNA
viruses, such as SARS-CoV-2, are well known to evolve rapidly by
mutation and hybridization (Holland et al. 1982), and the retention of
variants may facilitate retro-colonizing of humans from recent spillover
into other animal species. This perspective in phylogenetic conservatism
analyzed along with available empirical data (such as that of
Celorio-Mancera et al. 2016) and the real nature of novelty emergence
(i.e. which includes more than just the idea that adaptation is solely
associated with random mutations - Jablonka and Lamb 1995; Jablonka et
al. 2014; Agosta and Brooks 2020) may provide a better understanding on
the process of retro-colonization of the original host species/lineages.
Hence, retro-colonization should be an important element in
epidemiological monitoring (as suggested by Favoretto et al. 2019,
Franklin e Bevins 2020, and González-Salazar, Stephens, e
Sánchez-Cordero 2017), especially in cases of recent emergence and
re-emergence of EIDs.
The combined results of this study provide further theoretical support
for the assertion that “emerging infectious diseases are evolutionary
accidents waiting to happen” (Brooks and Ferrao 2005). An increase in
host-repertoire by pathogens, potentially associated with the emergence
of a new infectious disease, is most likely to occur among closely
related species of hosts, but it is also possible among distantly
related hosts when the resource(s) is(are) convergent (see discussion on
specilization in Brooks and McLennan 2002). Capacity is much
larger than we can anticipate, and it is the opportunity of
encounter (i.e. the breakdown in mechanisms for ecological isolation)
that is a more essential determinant to the emergence of new
associations (Araujo et al. 2015; Brooks et al. 2019; Agosta and Brooks
2020). And opportunities are more frequent during periods of
environmental disruptions, many of which are associated with
climatological fluctuations in the past (Hoberg and Klassen 2002; Brooks
and Hoberg 2007; Hoberg and Brooks 2008, 2015; Hoberg et al. 2017).
Climatological fluctuations usually change the permeability of
pre-existing ecological barriers and promote shuffling in the
composition of organismic communities, augmenting the rate of encounter
of different host lineages, many of the same clade, fostering intense
exchange in pathogens.
In general, climate oscillation and independent or accompanying
environmental disruptions over evolutionary time have been a central
determinant of opportunities for faunal mixing and pathogen exchange
that have structured complex associations (Hoberg and Brooks, 2008).
Climate and environmental disruption occur across scales and
historically have had a substantial episodic behavior in the past
(Hoberg et al. 2017). However, during what is now characterized as the
Anthropocene, the outcomes of environmental disruption have become
significantly more prevalent due to globalization, other
human-associated actions, and also to climate change, which promote
movements of wildlife, humans, and domestic species into new geographic
range (Wilson 1995; Brooks and Boeger 2019). As a consequence, we expect
EID’s to become even more frequent in the years to come (Brooks et al.
2014). We have little control over capacity, but we can, to a certain
level, monitor, avoid, and minimize the opportunity of encounter between
parasites and compatible host species. This is the principle of the
D.A.M.A. protocol (Brooks et al. 2014, 2019; Hoberg and Brooks 2015;
Brooks and Boeger 2019).
However, even with an effective D.A.M.A. protocol established, the task
to avoid the emergence of new diseases is especially difficult,
considering available empirical information. Many of the most
significant events in the history of life, and in the history of EID’s,
are likely the result of unpredictable incidents when compatible
biological entities unexpectedly meet (opportunity). Attempts to
generate new associations (hosts and pathogens, in this case) likely
occur continuously, most being unsuccessful. However, a single
successful event may perpetuate the emerged association through
evolution and have a significant influence on the future
diversifications of the associates. That was likely the case for
well-known symbioses, such as those of proto-eukaryotic cells and
mitochondria, eukaryotic cells, and chloroplasts but also for many
recent EIDs, such as HIV, Ebola, Dengue, Zika, Chikungunya, and, of
course, Covid19.
Perhaps the final message from the empirical information accumulated
from the recent emergence of infectious diseases and the dynamics
revealed from the theoretical framework of the Stockholm Paradigm
(Brooks et al. 2019) and associated evolutionary models (Araujo et al.
2015) is that we cannot “lower our guard”. These events are
evolutionarily dynamic processes, with pathogens incessantly exploring
the space of compatible host species (Brooks et al. 2019). And we – and
other domesticated species -are certainly one of the most abundant,
available, ecologically diverse, and widespread species of potential
host on this planet.