Genomic analysis of differentiation and demography of the formerly conspecific agile (Dipodomys agilis) and Dulzura (D. simulans) kangaroo rats.

Karyotype variation within Pacific kangaroo rat Dipodomys agilis motivated its division in 1997 into the agile kangaroo rat (AKR, D. agilis, 2N = 62) in the north of its range in California, and Dulzura kangaroo rat (DKR, D. simulans, 2N = 60) to the south, with a suspected sympatric zone south of the San Gabriel and San Bernardino Mountains.

The effect of body size and inbreeding on cancer mortality in breeds of the domestic dog: a test of the multi-stage model of carcinogenesis.

Cancer is a leading cause of death in domestic dogs. Deaths due to cancer vary widely among breeds, providing an opportunity for testing the multi-stage model of carcinogenesis. This model underpins evolutionary and basic studies of cancer suppression and predicts a linear increase in cancer with breed size, an expectation complicated by bigger breeds having a shorter lifespan (decreasing risk).

Cancer suppression and the evolution of multiple retrogene copies of TP53 in elephants: A re-evaluation.

Evolving to become bigger and/or longer lived should increase cancer susceptibility, but this predicted increase is not observed, a contradiction named Peto's paradox. A solution is that cancer suppression evolves to minimize cancer susceptibility, and the discovery of 19 retrogene (RTG) copies of the tumor suppressor gene TP53 in the African elephant () is increasingly cited as a classic example of such adaptive suppression. However, classic examples need rigorous evaluation and an alternative hypothesis is that the RTGs spread by genetic drift.

Telomeres, the loop tying cancer to organismal life-histories.

Recent developments in telomere and cancer evolutionary ecology demonstrate a very complex relationship between the need of tissue repair and controlling the emergence of abnormally proliferating cells. The trade-off is balanced by natural and sexual selection and mediated via both intrinsic and environmental factors. Here, we explore the effects of telomere-cancer dynamics on life history traits and strategies as well as on the cumulative effects of genetic and environmental factors.

Identifying key questions in the ecology and evolution of cancer.

The application of evolutionary and ecological principles to cancer prevention and treatment, as well as recognizing cancer as a selection force in nature, has gained impetus over the last 50 years. Following the initial theoretical approaches that combined knowledge from interdisciplinary fields, it became clear that using the eco-evolutionary framework is of key importance to understand cancer. We are now at a pivotal point where accumulating evidence starts to steer the future directions of the discipline and allows us to underpin the key challenges that remain to be addressed.

Determining cancer risk: the evolutionary multistage model or total stem cell divisions?

A recent hypothesis proposed that the total number of stem cell divisions in a tissue (TSCD model) determine its intrinsic cancer risk; however, a different model-the multistage model-has long been used to understand how cancer originates. Identifying the correct model has important implications for interpreting the frequency of cancers. Using worldwide cancer incidence data, we applied three tests to the TSCD model and an evolutionary multistage model of carcinogenesis (EMMC), a model in which cancer suppression is recognized as an evolving trait, with natural selection acting to suppress cancers causing a significant mean loss of Darwinian fitness.

Resolving Peto's paradox: Modeling the potential effects of size-related metabolic changes, and of the evolution of immune policing and cancer suppression.

The intrinsic risk of cancer increases with body size and longevity; however, big long-lived species do not exhibit this increase, a contradiction named Peto's paradox. Five hypotheses potentially resolving this paradox were modeled using the multistage model of carcinogenesis. The five hypotheses were based on (1) intrinsic changes in metabolic rate with body size; adaptive increase in immune policing of (2) cancer cells or (3) cells with driver mutations; or adaptive increase in cancer suppression via (4) decreased somatic mutation rate, or (5) increased genetic control.

A phylogenetic test of the role of CRISPR-Cas in limiting plasmid acquisition and prophage integration in bacteria.

CRISPR-Cas is a prokaryotic defense system capable of protecting the cell from damaging foreign genetic elements. However, some genetic elements can be beneficial, which suggests the hypothesis that bacteria with CRISPR-Cas incur a cost of reduced intake of mutualistic plasmids and prophage. Here we present the first robust test of this hypothesis that controls for phylogenic and ecological biases in the distribution of CRISPR-Cas.

An Experimental Test of the Host-Plant Range of Nonrecombinant Strains of North American Xylella fastidiosa subsp. multiplex.

Nonrecombinant strains of Xylella fastidiosa subsp. multiplex (those lacking evidence of significant intersubspecific homologous recombination) infect the xylem of a wide range of native and nonnative trees in North America. However, the degree to which different strains have a specialized host range remains poorly understood.

Size matters: height, cell number and a person's risk of cancer.

The multistage model of carcinogenesis predicts cancer risk will increase with tissue size, since more cells provide more targets for oncogenic somatic mutation. However, this increase is not seen among mammal species of different sizes (Peto's paradox), a paradox argued to be due to larger species evolving added cancer suppression. If this explanation is correct, the cell number effect is still expected within species.

Host and symbiont genetic contributions to fitness in a symbiosis.

The fitness effects associated with infection have wide-ranging ecological and evolutionary consequences for host species. How these effects are modulated by the relative influence of host and genomes has been described as a balancing act of genomic cooperation and conflict. For vertically transmitted symbionts, like cytoplasmic , concordant host-symbiont fitness interests would seem to select for genomic cooperation.

Overestimating the Role of Environment in Cancers.

In a recent article, Wu and colleagues (Nature 2016;529:43-47) review previous studies and present new estimates for the contribution of extrinsic factors to cancer development. The new estimates are generally close to 100%, even for bone and brain cancers that have no known associations with lifestyle and are typically not considered to be preventable. We find that the results of Wu and colleagues are incompatible with previous estimates derived from epidemiological and genetic data.

Adapting to a Changing Environment: Modeling the Interaction of Directional Selection and Plasticity.

Human-induced habitat loss and fragmentation constrains the range of many species, making them unable to respond to climate change by moving. For such species to avoid extinction, they must respond with some combination of phenotypic plasticity and genetic adaptation. Haldane's "cost of natural selection" limits the rate of adaptation, but, although modeling has shown that in very large populations long-term adaptation can be maintained at rates substantially faster than Haldane's suggested limit, maintaining large populations is often an impossibility, so phenotypic plasticity may be crucial in enhancing the long-term survival of small populations.

How Do Plant Diseases Caused by Xylella fastidiosa Emerge?

Emerging plant diseases frequently have significant economic, environmental, cultural, and social impacts. The prediction of new disease emergence, associated with new pathogens or not, remains a difficult and controversial topic. The main factors driving epidemics are often only identified several years after outbreaks, generally revealing that a limited number of factors are associated with the emergence of specific groups of pathogens.

The guardians of inherited oncogenic vulnerabilities.

Similar to seemingly maladaptive genes in general, the persistence of inherited cancer-causing mutant alleles in populations remains a challenging question for evolutionary biologists. In addition to traditional explanations such as senescence or antagonistic pleiotropy, here we put forward a new hypothesis to explain the retention of oncogenic mutations. We propose that although natural defenses evolve to prevent neoplasm formation and progression thus increasing organismal fitness, they also conceal the effects of cancer-causing mutant alleles on fitness and concomitantly protect inherited ones from purging by purifying selection.

The expression of tumour suppressors and proto-oncogenes in tissues susceptible to their hereditary cancers.

Background: Studies of familial cancers have found that only a small subset of tissues are affected by inherited mutations in a given tumour suppressor gene (TSG) or proto-oncogene (POG), even though the mutation is present in all tissues. Previous tests have shown that tissue specificity is not due to the presence vs absence of gene expression, as TSGs and POGs are expressed in nearly every type of normal human tissue. Using published microarray expression data we tested the related hypothesis that tissue-specific expression of a TSG or POG is highest in tissue where it is of oncogenic importance.

Peto's paradox and the promise of comparative oncology.

The past several decades have seen a paradigm shift with the integration of evolutionary thinking into studying cancer. The evolutionary lens is most commonly employed in understanding cancer emergence, tumour growth and metastasis, but there is an increasing realization that cancer defences both between tissues within the individual and between species have been influenced by natural selection. This special issue focuses on discoveries of these deeper evolutionary phenomena in the emerging area of 'comparative oncology'.

The complex biogeography of the plant pathogen Xylella fastidiosa: genetic evidence of introductions and Subspecific introgression in Central America.

The bacterium Xylella fastidiosa is a plant pathogen with a history of economically damaging introductions of subspecies to regions where its other subspecies are native. Genetic evidence is presented demonstrating the introduction of two new taxa into Central America and their introgression into the native subspecies, X. fastidiosa subsp.

Can neutral molecular markers be used to determine the success of an introduction of a "better" strain into an established population of a biocontrol parasitoid?

Neutral molecular markers are gene sequences where variants are considered to confer no fitness advantage, such as microsatellites and mitochondrial haplotypes. Several types of neutral marker are easy to develop, cheap to use, and have found extensive application for addressing ecological questions. In biocontrol, these markers are used to simplify identification of cryptic species and of prey remains in predators.

Large-scale intersubspecific recombination in the plant-pathogenic bacterium Xylella fastidiosa is associated with the host shift to mulberry.

Homologous recombination plays an important role in the structuring of genetic variation of many bacteria; however, its importance in adaptive evolution is not well established. We investigated the association of intersubspecific homologous recombination (IHR) with the shift to a novel host (mulberry) by the plant-pathogenic bacterium Xylella fastidiosa. Mulberry leaf scorch was identified about 25 years ago in native red mulberry in the eastern United States and has spread to introduced white mulberry in California.

Intersubspecific recombination in Xylella fastidiosa Strains native to the United States: infection of novel hosts associated with an unsuccessful invasion.

The bacterial pathogen Xylella fastidiosa infects xylem and causes disease in many plant species in the Americas. Different subspecies of this bacterium and different genotypes within subspecies infect different plant hosts, but the genetics of host adaptation are unknown. Here we examined the hypothesis that the introduction of novel genetic variation via intersubspecific homologous recombination (IHR) facilitates host shifts.

The real war on cancer: the evolutionary dynamics of cancer suppression.

Cancer is a disease of multicellular animals caused by unregulated cell division. The prevailing model of cancer (multistage carcinogenesis) is based on the view that cancer results after a series of (generally somatic) mutations that knock out the genetic mechanisms suppressing unregulated cell growth. The chance of these mutations occurring increases with size and longevity, leading to Peto's paradox: why don't large animals have a higher lifetime incidence of cancer than small animals? The solution to this paradox is evolution.

Seasonal stress drives predictable changes in inbreeding depression in field-tested captive populations of Drosophila melanogaster.

Recent meta-analyses conducted across a broad range of taxa have demonstrated a strong linear relationship between the change in magnitude of inbreeding depression under stress and stress level, measured as fitness loss in outbred individuals. This suggests that a general underlying response may link stress and inbreeding depression. However, this relationship is based primarily on laboratory data, and it is unknown whether natural environments with multiple stressors and fluctuating stress levels alter how stress affects inbreeding depression.