Asteroids and Pandemics

For whatever reason, viral disease and pandemics have been on my mind, so it’s no surprise that a recent paper in Molecular Ecology caught my attention. It blends the existential dread of global pandemics with the increasing panic concerning the effects of climate change on ocean ecosystems. Doesn’t that sound enticing?! (Incidentally, I’m not the only one fretting about this nexus. For a brief summary on instances of recent emergences of marine diseases, see this New York Times opinion piece.) But first, a little background.

The outbreak of sea star wasting disease (SSWD) on the western coast of the US was first noticed in 2013.  The disease affected 20 different species of sea stars, sub-tidal to intertidal, from the coast of Alaska to Baja, California with high mortality rates (67-99%, depending on the species). To date, there is some anecdotal accounts of recovery in small pockets, but not much.

FIGURE 1 from Hewson et al. (2014) showing A) an asymptomatic Sunflower sea star, Pycnopodia helianthoides B) an asymptomatic Ochre sea star, Pisaster ochraceus C) P. ochraceus succumbing to SSWD D) the geographic occurrences of SSWD and E) an electron transmission micrograph of icosahedral SSaDV virus particles recovered from an affected Evasterias troschelii sample.

Later inoculation experiments did not lead to disease induction in species other than Pycnopodia helianthoides (Hewson et al., 2018).  Further studies indicated a relationship between disease prevalence and ocean temperature (the outbreak happened to co-occur with the formation of the Pacific “blob”, a mass of warm ocean water that formed off the northwestern US coast in 2014-15), though that relationship was on a more local scale and may have more to do with thermal stress in general (both warm and cold) than warming ocean conditions (Miner et al., 2018). Differential gene expression (DGE) experiments between asymptomatic and symptomatic P. helianthoides produced signals in genes one would expect e.g. immune response, tissue remodeling, and apoptosis (Fuess et al., 2015; Gudenkauf & Hewson, 2015).  A population genomic study by Schiebelhut et al. (2018) compared pre- and post-outbreak allele frequencies in some populations of Pisaster ochraceus and found consistent differences among populations and life stages, suggesting selection has played a strong role in the genetic structure of the resulting populations.

The exact cause of SSWD remains elusive and is likely combined biological and environmental factors. Because of this ambiguity, SSWD has been re-branded as Asteroid Idiopathic Wasting Syndrome (AIWS). The science gods will surely be pleased with another acronym offering.

Now we have the recent paper by Ruiz-Ramos et al. (2020). The authors both produced and synthesized an impressive amount of genomic, transcriptomic, and SNP data to see if they could hone in on specific genes or genomic regions that are associated with AIWS, couching it as a “genomic autopsy” approach. As part of this effort, they sequenced ~90% of the genome of Pisaster ochraceus to act as a scaffold and generated RNA libraries from three different tissue types, four different size classes, and asymptomatic vs symptomatic. They compared the DGE patterns along with their chromosomal positions with previous transcriptome data from a DGE study between Pisaster ochraceus kept at ambient ocean temperature and those kept at 3+ degrees for several days, two previous studies of afflicted and unafflicted Pycnopodia helianthoides, and SNP data identifying outlier loci. It’s summed up in the very information-dense Figure 5 from the paper. There were 27 instances of three or more nuclear datasets yielding the same significantly up- or down-regulated genes, 12 of which corresponded to an annotated gene found in the Unitprot database. 

FIGURE 5 From Ruiz-Ramos et al. (2020): Comparisons of genomic and transcriptomic studies mapped to the Pisaster ochraceus nuclear and mitochondrial genomes. (a) Nuclear data sets, from the outside inwards: (i) position of the top discriminating loci in P. ochraceus (solid, exons; open, introns; light shading, outside of gene model; n = 99), *Indicates the three BayeScan outlier loci identified by Schiebelhut et al. (2018); (ii) DGE in smaller, relative to larger, P. ochraceus (FDR < 0.01), (iii) DGE between symptomatic and asymptomatic P. ochraceus (FDR < 0.01); (iv,v) DGE between symptomatic and asymptomatic P. helianthoides (Fuess et al. 2015; Gudenkauf and Hewson 2015; FDR < 0.01); (vi) DGE between ambient and elevated ocean temperature (+3°C) in P. ochraceus (FDR < 0.1; Chandler & Wares, 2017). (b) Mitochondrial data sets, from the outside inwards; icons correspond to those in panel A; DGE at FDR < 0.1. In both nuclear and mitochondrial data sets, orange, upregulated; blue, downregulated; black marks and salmon shading highlight nuclear loci recovered in ≥3 analyses (≥2 for mitochondria), or that overlapped between discriminant loci from Schiebelhut et al. (2018) and track c. Numbered bars correspond to Data set S7d.

In the nuclear genome, DGE analysis showed up-regulation of Caspace-1, the gene that sets apoptosis in motion, in symptomatic sea stars. Between all symptomatic and asymptomatic comparisons and all tissues, DGE was heightened genes associated with immune defense, cell adhesion, wound healing, and the innate immune system. In symptomatic individuals, genes involved with immune response were up-regulated. Because lectins demonstrated  down-regulation in the pyloric caecum and dermis of afflicted sea stars, the authors posit that AIWS is not of bacterial origin (certain lectin genes are involved in antimicrobial activity). The authors found a DGE signal at some of the outlier loci (and putatively under selection) previously described in Schiebelhut et al. (2018) between symptomatic and asymptomatic P. ochraceus, including up-regulation of GTP-binding protein in individuals afflicted with AIWS, suggesting there could be a link between genotypic variation and gene expression associated with AIWS.

Within the mitochondrial genome, six genes showed significant DGE patterns in two or more datasets. The gene 12S s-rRNA, was up-regulated in all three tissues in afflicted P. ochraceus relative to unafflicted individuals. Another mitochondrial gene, 16S L-rRNA, was up-regulated in both symptomatic and heat-treated P. ochraceus while tRNA-Asp was up-regulated in heat treated stars. Conversely, three genes (ATP6, ND2, ND5), were down-regulated relative to sea stars kept at ambient temperature. Also, the authors discovered a synonymous substitution in ND5 in both adult and juvenile survivors that was not found in pre-outbreak populations. Furthermore, all sea stars exposed to higher temperature displayed down-regulated ND5 expression relative to those at ambient ocean temperature.

As far as physical distribution of genes and loci within the genome, the main outlier loci of Schiebelhut et al. (2018) were randomly distributed among chromosomes as were the loci differentially expressed between symptomatic and asymptomatic individuals. The loci with DGE pattern after heat treatment, however, were clustered on chromosome 19 and loci that were differentially expressed by size were clustered on chromosomes 16 and 18–20.  Within the tissues of the sea stars, the pyloric caecum (part of the stomach that secretes digestive enzymes and absorbs nutrients) shows the greatest number of transcripts being differentially expressed between symptomatic and asymptomatic P. ochraceus. The dermis, where lesions occur in afflicted stars, also has a high DGE between symptomatic and asymptomatic P. ochraceus.

By performing this “genomic autopsy” on sea stars and incorporating previous results with new data, the authors make great strides toward uncovering genomic regions of interest that may lead to definitive causes or pathways or mechanisms behind the heterogeneous response to AIWS.  The massive die offs of sea stars has had far reaching and devastating consequences for marine ecosystems. Anyone who’s taken a marine ecology class knows the role that sea stars play as keystone species. Without them, mussels crowd out other invertebrates in the intertidal and sea urchins graze kelp into oblivion in subtidal and near shore coastal communities. Figuring out the best way to eradicate this disease or mitigate its effects will have positive ripple effects throughout marine ecosystems.

In closing, I feel like I would be remiss not to mention a more recent paper that has come out in Nature that takes a different approach by combining oceanographic and epidemiological data to model possible transmission pathways of SSWD/AIWS. The authors contrast three different models: infection and pathogenicity are constant and dispersal occurs via ocean currents, transmission rate is a function of temperature, and pathogenicity is a function of thermal stress. They found that models that associated mortality with sea surface temperature were more concordant with observed presence/absence data of SSWD up and down the Pacific US coast. While this type of study is outside of the purview of molecular ecology, since we’ve all found ourselves to be arm chair epidemiologists and modelers in The After Times, COVID19 year I, I’m sure we can all digest and even opine on its robustness from a safe distance.


Fuess, L. E., Eisenlord, M. E., Closek, C. J., Tracy, A. M., Mauntz, R., Gignoux-Wolfsohn, S., … Roberts, S. B. (2015). Up in arms: Immune and nervous system response to sea star wasting disease. PLoS ONE, 10(7), e0133053.

Gudenkauf, B. M., & Hewson, I. (2015). Metatranscriptomic analysis of Pycnopodia helianthoides (Asteroidea) affected by sea star wasting disease. PLoS ONE, 10(5), e0128150.

Hewson, I., Bistolas, K. S. I., Quijano Cardé, E. M., Button, J. B., Foster, P. J., Flanzenbaum, J. M., … Lewis, C. K. (2018). Investigating the complex association between viral ecology, environment, and Northeast Pacific Sea Star Wasting. Frontiers in Marine Science, 5, 77.

Hewson, I., Button, J. B., Gudenkauf, B. M., Miner, B., Newton, A. L., Gaydos, J. K., … Harvell, C. D. (2014). Densovirus associated with sea-star wasting disease and mass mortality. Proceedings of the National Academy of Sciences, 111(48), 17278–17283.

Miner CM, Burnaford JL, Ambrose RF, Antrim L, Bohlmann H, Blanchette CA, et al. (2018) Large-scale impacts of sea star wasting disease (SSWD) on intertidal sea stars and implications for recovery. PLoS ONE 13(3): e0192870.

Ruiz‐Ramos, DV,  Schiebelhut, LM,  Hoff, KJ,  Wares, JP,  Dawson, MN. (2020) An initial comparative genomic autopsy of wasting disease in sea stars. Molecular Ecology.  29: 1087– 1102.

Schiebelhut, L. M., Puritz, J. B., & Dawson, M. N. (2018). Decimation by sea star wasting disease and rapid genetic change in a keystone species, Pisaster ochraceus. Proceedings of the National Academy of Sciences, 115(27), 7069–7074.

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