Biology subjects

Santander, C. G.

Publications and source records attributed to Santander, C. G..

7 recordsLinked to original sources

bioRxiv2024

Detecting epidemic-driven selection: a simulation-based tool to optimize sampling design and analysis strategies

Throughout history, populations from numerous species have been decimated by epidemic outbreaks, like the 19th-century rinderpest outbreak in Cape buffalo ({approx} 90% mortality) and Black Death in humans ({approx} 50% mortality). Recent studies have raised the enticing idea that such epidemic outbreaks have led to strong natural selection acting on disease-protective variants in the host populations. However, so far there are few, if any, clear examples of such selection having taken place. This could be because so far studies have not had sufficient power to detect the type of selection an epidemic outbreak must induce: strong but extremely short-term selection on standing variation. We present here a simulation-framework that allows users to explore under what circumstances it is possible to detect epidemic-driven selection using standard selection scan methods like FSTand iHS. Using two examples, we illustrate how the framework can be used. Furthermore, via these examples, we show that comparing survivors to the dead has the potential to render higher power than more commonly used sampling schemes. And importantly, we show that even for outbreaks with high mortality, like the Black Death, strong selection may have led to only modest shifts in allele frequency, suggesting large sample sizes are required to obtain appropriate power to detect the selection. We hope this framework can help in designing well-powered future studies and thus lead to a clarification of the role epidemic-driven selection has played in the evolution of different species. Significance StatementOur study introduces a simulation-based framework, SimOutbreakSelection (SOS), which enables researchers to design studies that have power to detect epidemic-driven selection while taking sampling time points and demographic history into account. We use rinderpest in African Buffalo and the Black Death in Medieval Sweden as examples to showcase the framework. Via these examples we also show that large sample sizes are needed even for severe epidemics like the Black Death and that the often used sampling strategy where samples from before the epidemic and samples from after are compared is not always optimal.

evolutionary biology↗

bioRxiv2024

Extensive population structure highlights an apparent paradox of stasis in the impala (Aepyceros melampus)

Impalas are unusual among bovids because they have remained morphologically similar over millions of years - a phenomenon referred to as evolutionary stasis. Here, we sequenced 119 whole genomes from the two extant subspecies of impala, the common (Aepyceros melampus melampus) and black-faced (A. m. petersi) impala. We investigated the evolutionary forces working within the species to explore how they might be associated with its evolutionary stasis as a taxon. Despite being one of the most abundant bovid species, we found low genetic diversity overall, and a phylogeographic signal of spatial expansion from southern to eastern Africa. Contrary to expectations under a scenario of evolutionary stasis, we found pronounced genetic structure between and within the two subspecies with indications of ancient, but not recent, gene flow. Black-faced impala and eastern African common impala populations had more runs of homozygosity than common impala in southern Africa, and, using a proxy for genetic load, we found that natural selection is working less efficiently in these populations compared to the southern African populations. Together with the fossil record, our results are consistent with a fixed-optimum model of evolutionary stasis, in which impalas in the southern African core of the range are able to stay near their evolutionary fitness optimum as a generalist ecotone species, whereas eastern African impalas may struggle to do so due to the effects of genetic drift and reduced adaptation to the local habitat, leading to recurrent local extinction in eastern Africa and re-colonization from the South.

evolutionary biology↗

bioRxiv2023

African bush pigs exhibit porous species boundaries and appeared in Madagascar concurrently with human arrival

Several African mammals exhibit a phylogeographic pattern where closely related taxa are split between West/Central and East/Southern Africa, but their evolutionary relationships and histories remain controversial. Bushpigs (Potamochoerus larvatus) and red river hogs (P. porcus) are recognised as separate species due to morphological distinctions, a perceived lack of interbreeding at contact, and putatively old divergence times, but historically, they were considered conspecific. Moreover, the presence of Malagasy bushpigs as the sole large terrestrial mammal shared with the African mainland raises intriguing questions about its origin and arrival in Madagascar. Analyses of 67 whole genomes revealed a genetic continuum between the two species, with putative signatures of historical gene flow, variable FST values, and a recent divergence time (<500,000 years). Thus, our study challenges key arguments for splitting Potamochoerus into two species and suggests their speciation might be incomplete. Our findings also indicate that Malagasy bushpigs diverged from southern African populations and underwent a limited bottleneck 1,000-5,000 years ago, concurrent with human arrival in Madagascar. These results shed new light on the evolutionary history of an iconic and widespread African genus and provide insight into the longstanding biogeographic puzzle surrounding the bushpigs presence in Madagascar.

evolutionary biology↗

bioRxiv2023

Insufficient evidence for natural selection associated with the Black Death

Klunk et al. analyzed ancient DNA data from individuals in London and Denmark before, during and after the Black Death [1], and argued that allele frequency changes at immune genes were too large to be produced by random genetic drift and thus must reflect natural selection. They also identified four specific variants that they claimed show evidence of selection including at ERAP2, for which they estimate a selection coefficient of 0.39-several times larger than any selection coefficient on a common human variant reported to date. Here we show that these claims are unsupported for four reasons. First, the signal of enrichment of large allele frequency changes in immune genes comparing people in London before and after the Black Death disappears after an appropriate randomization test is carried out: the P value increases by ten orders of magnitude and is no longer significant. Second, a technical error in the estimation of allele frequencies means that none of the four originally reported loci actually pass the filtering thresholds. Third, the filtering thresholds do not adequately correct for multiple testing. Finally, in the case of the ERAP2 variant rs2549794, which Klunk et al. show experimentally may be associated with a host interaction with Y. pestis, we find no evidence of significant frequency change either in the data that Klunk et al. report, or in published data spanning 2,000 years. While it remains plausible that immune genes were subject to natural selection during the Black Death, the magnitude of this selection and which specific genes may have been affected remains unknown.

genomics↗

bioRxiv2022

Multiple paths towards repeated phenotypic evolution in the spiny-leg adaptive radiation (Tetragnatha; Hawaii)

The repeated evolution of phenotypes is ubiquitous in nature and offers some of the clearest evidence of the role of natural selection in evolution. The genomic basis of repeated phenotypic evolution is often complex and can arise from a combination of gene flow, shared ancestral polymorphism and de novo mutation. Here, we investigate the genomic basis of repeated ecomorph evolution in the adaptive radiation of the Hawaiian spiny-leg Tetragnatha. This radiation comprises four ecomorphs that are microhabitat-specialists, and differ in body pigmentation and size (Green, Large Brown, Maroon, and Small Brown). Using 76 newly generated low-coverage, whole-genome resequencing samples, coupled with population genomic and phylogenomic tools, we studied the evolutionary history of the radiation to understand the evolution of the spiny-leg lineage and the genetic underpinnings of ecomorph evolution. Congruent with previous works, we find that each ecomorph has evolved twice, with the exception of the Small Brown ecomorph, which has evolved three times. The evolution of the Maroon and the Small Brown ecomorphs likely involved ancestral hybridization events, whereas the Green and the Large Brown ecomorphs likely evolved because of either standing genetic variation or de novo mutation. Pairwise comparisons of ecomorphs based on the fixation index (FST) show that divergent genomic regions include genes with functions associated with pigmentation (melanization), learning, neuronal and synapse activity, and circadian rhythms. These results show that the repeated evolution of ecomorphs in the Hawaiian spiny-leg Tetragnatha is linked to multiple genomic regions and suggests a previously unknown role of learning and circadian rhythms in ecomorph.

evolutionary biology↗

bioRxiv2018

HERV-K HML-2 transcription in diverse cancers is related with cancer stem cell and epithelial-mesenchymal transition markers

Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections that make up 8% of the human genome. Although these elements are mostly fragmented and inactive, many proviruses belonging to the HERV-K (HML-2) family, the youngest lineage in the human genome, have intact open reading frames, some encoding for accessory genes called np9 and rec that interact with oncogenic pathways. Many studies have established that ERVs are transiently expressed in both stem cells and cancer, resulting in aberrant self-renewal and uncontrolled proliferation. np9 and rec expression are significantly correlated with a range of cancer stem cell (CSC) and epithelial to mesenchymal transition (EMT) biomarkers, including cellular receptors, transcription factors, and histone modifiers. Surprisingly, these ERV genes are negatively correlated with genes known to promote pluripotency in embryonic stem cell lines, such as Oct4. These results indicate that HERV-K (HML-2) is part of the transcriptional landscape responsible for cancer cells undergoing the phenotypic switch that characterises EMT. The discovery of np9 and recs correlation with CSC and EMT biomarkers suggest a yet undescribed role affecting the transitional CSC-like state in EMT and the shift towards cancer malignancy.\n\nImportanceIn this study, we find that human endogenous retrovirus HERV-K (HML-2)-encoded genes np9 and rec are correlated with the expression of many biomarkers associated with cancer stem cells (CSC) and epithelial-mesenchymal transition (EMT). There has been a significant effort to develop novel treatments targeting CSC and EMT-specific signalling pathways and cell surface markers. This research describes HERV-K (HML-2) as interacting or being part of the regulatory network that make up reversible cell state switching in EMT. Our findings suggest these specific HERVs may be good candidate biomarkers in identifying the transitional CSC-like states that are present during the progression of EMT and cancer metastasis.

bioinformatics↗

bioRxiv2018

Targeting endogenous retrovirus gene transcription in human cancers

Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections that make up to 8% of the human genome. Although these elements are mostly fragmented and inactive, many proviruses belonging to the HERV-K (HML-2) family, the only lineage still proliferating in the genome after the human-chimpanzee split, have intact open reading frames, some encoding for accessory genes called np9 and rec that interact with oncogenic pathways. Many studies have established that the transient expression of ERVs are in both stem cells and cancers results in aberrant self-renewal and uncontrolled proliferation.\n\nThe wealth of high-quality genomic and transcriptomic Illumina sequence data available from The Cancer Genome Atlas (TCGA) that are sequenced from a diversity of different tumour types makes it a valuable resource in cancer research. However, there is currently no universal computational method for inferring expression of specific repetitive elements from RNA-seq data, such as genes encoded by HERV-K (HML-2).\n\nThis study presents a novel and a highly specific pipeline that is able to capture and measure transcription of np9 and rec encoded by proviruses that share great sequence similarity, and are transcribed at very low levels. We show by using our novel methodology that np9 and rec are overexpressed in breast cancer, germ cell tumours, skin melanoma, lymphoma, ovarian cancer, and prostate cancer compared to non-diseased tissues. We also show that np9 and rec are specifically expressed in the 8 and 16-cell stage in human preimplantation embryos.

bioinformatics↗