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11 May 2024
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The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics

Informed Choices, Cohesive Future: Decisions and Recommendations for ERGA

Recommended by ORCID_LOGO based on reviews by Justin Ideozu and Eric Crandall

The European Reference Genome Atlas (ERGA) (Mc Cartney et al, 2024, Mazzoni et al, 2023) demonstrates the collaborative spirit and intellectual abilities of researchers from 33 European countries. This ambitious project, which is part of the Earth BioGenome Project (Lewin et al., 2018) Phase II, has embarked on an unprecedented mission: to decipher the genetic makeup of 150,000 species over a span of four years. At the heart of ERGA is a decentralized pilot infrastructure specifically built to assist the production of high-quality reference genomes. This structure acts as a scaffold for the massive task of genome sequencing, giving the necessary framework to manage the complexity of genomic research. The research paper under consideration offers a comprehensive narrative of ERGA's evolution, outlining both successes and challenges encountered along the road. 

One of the most significant issues addressed in the manuscript is the equitable distribution of resources and expertise among participating laboratories and countries. In a project of this magnitude, it is critical to leverage the pooled talents and capacities of researchers from across Europe. ERGA's pan-European network promotes communications and collaboration, creating an environment in which knowledge flows freely and barriers are overcome. This adoption of strong coordination and communication tactics will be essential to ERGA's success. Scientific collaboration depends on efficient communication channels because they allow researchers to share resources, collaborate on new initiatives, and exchange ideas. Through a diverse range of gatherings, courses, and virtual discussion boards, ERGA fosters an environment of transparency and cooperation among members, enabling scientists to overcome challenges and make significant discoveries. The importance ERGA places on training and information transfer programmes is a pillar of its strategy. Understanding the importance of capacity development, ERGA invests in providing researchers with the knowledge and abilities necessary for effectively navigating the complicated terrain of genomic research. A wide range of subjects are covered in training programmes (Larivière et al. 2023), from sample preparation and collection to data processing methods and sequencing technology. Through the development of a group of highly qualified experts, ERGA creates the foundation for continued advancement and creativity in the genomics sector.

This manuscript also covers in detail the technological workflows and sequencing techniques used in ERGA's pilot infrastructure. With the aid of cutting-edge sequencing technologies based on both long-read and short-read sequencing, they are working to unravel the complex structure of the genetic code with a level of accuracy and precision never before possible. To guarantee the accuracy of genetic data and prevent mistakes and flaws that can jeopardize the findings' integrity, quality control methods are put in place. Despite having a focus on genome sequencing due to its technological complexities, ERGA also remains firm in its dedication to metadata collection and sample validation. Metadata serves as a critical link between raw genetic data and useful scientific insights, giving necessary context and allowing researchers to draw practical findings from their investigations. Sample validation approaches improve the reliability and reproducibility of the results, providing users confidence in the quality of the genetic data provided by ERGA.​

Looking ahead, ERGA envisions its decentralized infrastructure serving as a model for global collaborative research efforts. By embracing diversity, encouraging cooperation, and pushing for open access to data and resources, ERGA hopes to catalyze scientific discovery and generate positive change in the field of biodiversity genomics. ERGA aims to promote a more equitable and sustainable future for all by ongoing interaction with stakeholders, intensive outreach and education activities, and policy change advocacy. In addition to its immediate goals, ERGA considers the long-term implications of its work. As genomic technology progresses, the potential application of high-quality reference genomes will continue to grow. From informing conservation efforts and illuminating evolutionary histories to revolutionizing healthcare and agriculture, it is likely that ERGA's contributions will have far-reaching consequences for people and the planet as a whole.​

Furthermore, ERGA understands the importance of interdisciplinary collaboration in addressing the difficult challenges of the twenty-first century. ERGA aims to integrate genetic research into larger initiatives to promote sustainability and biodiversity conservation by forming relationships with stakeholders from other areas, such as policymakers, conservationists, and indigenous groups. Through shared knowledge and community action, ERGA seeks to create a future in which mankind coexists peacefully with the natural world, guided by a thorough grasp of its genetic legacy and ecological interconnectivity.

Finally, the manuscript exemplifies ERGA's collaborative ambitions and achievements, capturing the spirit of creativity and collaboration that defines this ground-breaking effort. As ERGA continues to push the boundaries of genetic research, it remains dedicated to scientific excellence, inclusivity, and the quest of knowledge for the benefit of society. I wholeheartedly recommend the publication of this groundbreaking initiative, offering my enthusiastic endorsement for its valuable contribution to the scientific community.​​

References
Larivière, D., Abueg, L., Brajuka, N. et al. (2024). Scalable, accessible and reproducible reference genome assembly and evaluation in Galaxy. Nature Biotechnology 42, 367-370. https://doi.org/10.1038/s41587-023-02100-3

Lewin, H. A., Robinson, G. E., Kress, W. J., Baker, W. J., Coddington, J., Crandall, K. A., Durbin, R., Edwards, S. V., Forest, F., Gilbert, M. T. P., Goldstein, M. M., Grigoriev, I. V., Hackett, K. J., Haussler, D., Jarvis, E. D., Johnson, W. E., Patrinos, A., Richards, S., Castilla-Rubio, J. C., … Zhang, G. (2018). Earth BioGenome Project: Sequencing life for the future of life. Proceedings of the National Academy of Sciences, 115(17), 4325–4333. https://doi.org/10.1073/pnas.1720115115

Mazzoni, C. J., Claudio, C.i, Waterhouse, R. M. (2023). Biodiversity: an atlas of European reference genomes. Nature 619 : 252-252. https://doi.org/10.1038/d41586-023-02229-w

Mc Cartney, A. M., Formenti, G., Mouton, A., Panis, D. de, Marins, L. S., Leitão, H. G., Diedericks, G., Kirangwa, J., Morselli, M., Salces-Ortiz, J., Escudero, N., Iannucci, A., Natali, C., Svardal, H., Fernández, R., Pooter, T. de, Joris, G., Strazisar, M., Wood, J., … Mazzoni, C. J. (2024). The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics. bioRxiv, ver. 4 peer-reviewed and recommended by Peer Community in Genomics. https://doi.org/10.1101/2023.09.25.559365

The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomicsAnn M Mc Cartney, Giulio Formenti, Alice Mouton, Claudio Ciofi, Robert M Waterhouse, Camila J Mazzoni, Diego De Panis, Luisa S Schlude Marins, Henrique G Leitao, Genevieve Diedericks, Joseph Kirangwa, Marco Morselli, Judit Salces, Nuria Escudero, ...<p>English: A global genome database of all of Earth's species diversity could be a treasure trove of scientific discoveries. However, regardless of the major advances in genome sequencing technologies, only a tiny fraction of species have genomic...Bioinformatics, ERGA PilotJitendra Narayan Justin Ideozu, Eric Crandall2023-10-01 01:03:58 View
26 Jun 2024
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Transposable element expression with variation in sex chromosome number supports a toxic Y effect on human longevity

The number of Y chromosomes is positively associated with transposable element expression in humans, in line with the toxic Y hypothesis

Recommended by ORCID_LOGO based on reviews by 3 anonymous reviewers

The study of human longevity has long been a source of fascination for scientists, particularly in relation to the genetic factors that contribute to differences in lifespan between the sexes. One particularly intriguing area of research concerns the Y chromosome and its impact on male longevity. The Y chromosome expresses genes that are essential for male development and reproduction. However, it may also influence various physiological processes and health outcomes. It is therefore of great importance to investigate the impact of the Y chromosome on longevity. This may assist in elucidating the biological mechanisms underlying sex-specific differences in aging and disease susceptibility. As longevity research progresses, the Y chromosome's role presents a promising avenue for elucidating the complex interplay between genetics and aging.

Transposable elements (TEs), often referred to as "jumping genes", are DNA sequences that can move within the genome, potentially causing mutations and genomic instability. In young, healthy cells, various mechanisms, including DNA methylation and histone modifications, suppress TE activity to maintain genomic integrity. However, as individuals age, these regulatory mechanisms may deteriorate, leading to increased TE activity. This dysregulation could contribute to age-related genomic instability, cellular dysfunction, and the onset of diseases such as cancer. Understanding how TE repression changes with age is crucial for uncovering the molecular underpinnings of aging (De Cecco et al. 2013; Van Meter et al. 2014).

The lower recombination rates observed on Y chromosomes result in the accumulation of TE insertions, which in turn leads to an enrichment of TEs and potentially higher TE activity. To ascertain whether the number of Y chromosomes is associated with TE activity in humans, Teoli et al. (2024) studied the TE expression level, as a proxy of the TE activity, in several karyotype compositions (i.e. with differing numbers of Y chromosomes). They used transcriptomic data from blood samples collected in 24 individuals (six females 46,XX, six males 46,XY, eight males 47,XXY and four males 47,XYY). Even though they did not observe a significant correlation between the number of Y chromosomes and TE expression, their results suggest an impact of the presence of the Y chromosome on the overall TE expression. The presence of Y chromosomes also affected the type (family) of TE present/expressed. To ensure that the TE expression level was not biased by the expression of a gene in proximity due to intron retention or pervasive intragenic transcription, the authors also tested whether the TE expression variation observed between the different karyotypes could be explained by gene (i.e. here non-TE gene) expression. 

As TE repression mechanisms are known to decrease over time, the authors also tested whether TE repression is weaker in older individuals, which would support a compelling link between genomic stability and aging. They investigated the TE expression differently between males and females, hypothesizing that old males should exhibit a stronger TE activity than old females. Using selected 45 males (47,XY) and 35 females (46,XX) blood samples of various ages (from 20 to 70) from the Genotype-Tissue Expression (GTEx) project, the authors studied the effect of age on TE expression using 10-year range to group the study subjects. Based on these data, they fail to find an overall increase of TE expression in old males compared to old females.

Notwithstanding the small number of samples, the study is well-designed and innovative, and its findings are highly promising. It marks an initial step towards understanding the impact of Y-chromosome ‘toxicity’ on human longevity. Despite the relatively small sample size, which is a consequence of the difficulty of obtaining samples from individuals with sex chromosome aneuploidies, the results are highly intriguing and will be of interest to a broad range of biologists.

                                             

References

De Cecco M, Criscione SW, Peckham EJ, Hillenmeyer S, Hamm EA, Manivannan J, Peterson AL, Kreiling JA, Neretti N, Sedivy JM (2013) Genomes of replicatively senescent cells undergo global epigenetic changes leading to gene silencing and activation of transposable elements. Aging Cell, 12, 247–256. https://doi.org/10.1111/acel.12047

Teoli J, Merenciano M, Fablet M, Necsulea A, Siqueira-de-Oliveira D, Brandulas-Cammarata A, Labalme A, Lejeune H, Lemaitre J-F, Gueyffier F,  Sanlaville D, Bardel C, Vieira C, Marais GAB, Plotton I (2024) Transposable element expression with variation in sex chromosome number supports a toxic Y effect on human longevity. bioRxiv, ver. 5 peer-reviewed and recommended by Peer Community in Genomics. https://doi.org/10.1101/2023.08.03.550779

Van Meter M, Kashyap M, Rezazadeh S, Geneva AJ, Morello TD, Seluanov A,  Gorbunova V (2014) SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age. Nature Communications, 5, 5011. https://doi.org/10.1038/ncomms6011

 

 

Transposable element expression with variation in sex chromosome number supports a toxic Y effect on human longevityJordan Teoli, Miriam Merenciano, Marie Fablet, Anamaria Necsulea, Daniel Siqueira-de-Oliveira, Alessandro Brandulas-Cammarata, Audrey Labalme, Hervé Lejeune, Jean-François Lemaitre, François Gueyffier, Damien Sanlaville, Claire Bardel, Cristina Vi...<p>Why women live longer than men is still an open question in human biology. Sex chromosomes have been proposed to play a role in the observed sex gap in longevity, and the Y male chromosome has been suspected of having a potential toxic genomic ...Evolutionary genomicsAnna-Sophie Fiston-LavierAnonymous, Igor Rogozin , Paul Jay , Anonymous2023-08-18 15:01:38 View
28 Nov 2024
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Factors influencing the accuracy and precision in dating single gene trees

Dating single gene trees in the age of phylogenomics

Recommended by based on reviews by Sishuo Wang, David Duchêne and 1 anonymous reviewer

Dating evolutionary trees is a critical task that allows us to connect biological history to ecological and geological events, helping us explore connections between environmental change and genetic innovations. The central idea behind these techniques is to link changes at the sequence level to divergence times, under the general assumption that substitutions accumulate steadily over time. So, sequences that diverged earlier are expected to be more different than sequences that diverged more recently. For a number of biological and statistical reasons, the relationship between sequence divergence and time is not linear, so it is not always the case that more divergent sequences have accumulated more substitutions than less divergent ones. In the case of organismal-level divergences, a natural approach to mitigate these challenges is to incorporate as many genes as possible into the analyses. However, this route is not available when we are focusing our interest on a single gene or a gene family. Thus, exploring how different features of single gene trees impact the accuracy and precision of divergence time estimates is of interest. In this study, Louvel and Roest Crollius (2024), select a well-studied group of mammals, primates, extract single copy genes from their genomes, and explore how different factors such as alignment size, evolutionary rate variation and discordance between the gene and species trees impact divergence time estimates. 

There are many strengths of this study. The central ones are the number of factors considered and the transparent discussion of the limitations. In this regard, the study is an elegant combination of empirical and simulated data. Some of the results match intuitive expectations. For example, the authors find that longer alignments are more informative than shorter ones, that differences in evolutionary rate among branches lead to loss in precision, and that slow-evolving genes perform worse. Intriguingly, they also find differences in performance among genes with different ontologies. The empirical data used in this study is limited to a single group, and generally considers genes that have apparently remained as single copies. Accordingly, the conclusions that can be drawn are somewhat limited, calling for future studies building on and expanding the concepts of the study by Louvel and colleagues. For example, including genes that have been lost or duplicated would be of interest because changes in gene complement are a prevalent source of variation at the genome level in mammals in general (Demuth et al. 2006), and particularly in primates (Hahn et al. 2007).

                        

References

Demuth JP, De Bie T, Stajich JE, Cristianini N, Hahn MW (2006) The evolution of mammalian gene families. PLoS One, e85. https://doi.org/10.1371/journal.pone.0000085

Hahn MW, Demuth JP, Han SG (2007) Accelerated rate of gene gain and loss in primates. Genetics, 177,1941-1949. https://doi.org/10.1534/genetics.107.080077

Louvel, G and Roest Crollius, H (2024) Factors influencing the accuracy and precision in dating single gene trees. bioRxiv, ver. 6 peer-reviewed and recommended by PCI Genomics. https://doi.org/10.1101/2020.08.24.264671

 

Factors influencing the accuracy and precision in dating single gene treesGuillaume Louvel and Hugues Roest Crollius<p>Molecular dating is the inference of divergence time from genetic sequences. Knowing the time of appearance of a taxon sets the evolutionary context by connecting it with past ecosystems and species. Knowing the divergence times of gene lineage...Bioinformatics, Evolutionary genomics, VertebratesFederico Hoffmann2023-08-15 12:06:09 View
06 Feb 2024
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The need of decoding life for taking care of biodiversity and the sustainable use of nature in the Anthropocene - a Faroese perspective

Why sequence everything? A raison d’être for the Genome Atlas of Faroese Ecology

Recommended by ORCID_LOGO based on reviews by Tereza Manousaki and 1 anonymous reviewer

When discussing the Earth BioGenome Project with scientists and potential funding agencies, one common question is: why sequence everything? Whether sequencing a subset would be more optimal is not an unreasonable question given what we know about the mathematics of importance and Pareto’s 80:20 principle, that 80% of the benefits can come from 20% of the effort. However, one must remember that this principle is an observation made in hindsight and selecting the most effective 20% of experiments is difficult. As an example, few saw great applied value in comparative genomic analysis of the archaea Haloferax mediterranei, but this enabled the discovery of CRISPR/Cas9 technology (1). When discussing whether or not to sequence all life on our planet, smaller countries such as the Faroe Islands are seldom mentioned. 
 
Mikalsen and co-authors (2) provide strong arguments to appreciate, investigate and steward genetic diversity, from a Faroese viewpoint, a fishery viewpoint, and a global viewpoint. As readers, we learn to cherish the Faroe Islands, the Faroese, and perhaps by extension all of nature and the people of the world. The manuscript describes the proposed Faroese participation in the European Reference Genome Atlas (ERGA) consortium through Gen@FarE – the Genome Atlas of Faroese Ecology. Gen@FarE aims to: i) generate high-quality reference genomes for all eukaryotes on the islands and in its waters; ii) establish population genetics of all species of commercial or ecological interest; and iii) establish a “databank” for all Faroese species with citizen science tools for participation.


In the background section of the manuscript, the authors argue that as caretakers of the earth (and responsible for the current rapid decrease in biodiversity), humanity must be aware of the biodiversity and existing genetic diversity, to protect these for future generations. Thus, it is necessary to have reference genomes for as many species as possible, enabling estimation of population sizes and gene flow between ecosystem locations. Without this the authors note that “…it is impossible to make relevant management plans for a species, an ecosystem or a geographical area…”. Gen@FarE is important. The Faroe nation has a sizable economic zone in the North Atlantic and large fisheries. In terms of biodiversity and conservation, the authors list some species endemic to other Faroe islands, especially sea birds. The article discusses ongoing marine environmental-DNA-based monitoring programs that started in 2018, and how new reference genome databases will help these efforts to track and preserve marine biodiversity. They point to the lack of use of population genomics information for Red List decisions on which species are endangered, and the need for these techniques to inform sustainable harvesting of fisheries, given collapses in critical food species such as Northwest Atlantic cod and herring. In one example, they highlight how the herring chromosome 12 inversion contains a “supergene” collection of tightly linked genes associated with ecological adaptation. Genetic tools may also help enable the identification and nurturing of feeding grounds for young individuals. Critically, the Faroe Islands have a significant role to play in protecting the millions of tons of seafood caught annually upon which humanity relies. As the authors note, population genomics based on high-quality reference sequences is “likely the best tool” to monitor and protect commercial fisheries. There is an important section discussing the role of interactions between visible and “invisible" species in the marine ecosystem on which we all depend. Examples of “invisible” species include a wide range of morphologically similar planktonic algae, and invasive species transported by ballast water or ship hulls.​ As biologists, I believe we forget that our population studies of life on the earth have so far been mostly in the dark. Gen@FarE is but one light that can be switched on. 


The authors conclude by discussing Gen@FarE plans for citizen science and education, perhaps the most important part of this project if humanity is to learn to cherish and care for the earth. Where initiatives such as the Human Genome Project did not need the collaborative efforts of the world for sample access, the Earth BioGenome Project most certainly does. In the same way, at a smaller scale, Gen@FarE requires the support and determination of the Faroese. 
 


References    

1          Mojica, F. J., Díez-Villaseñor, C. S., García-Martínez, J. & Soria, E. Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J Mol Evol 60, 174-182 (2005).

2          Mikalsen, S-O., Hjøllum, J. í., Salter, I., Djurhuus, A. & Kongsstovu, S. í. The need of decoding life for taking care of biodiversity and the sustainable use of nature in the Anthropocene – a Faroese perspective. EcoEvoRxiv (2024), ver. 3 peer-reviewed and recommended by Peer Community in Genomics. https://doi.org/10.32942/X21S4C

The need of decoding life for taking care of biodiversity and the sustainable use of nature in the Anthropocene - a Faroese perspectiveSvein-Ole Mikalsen, Jari í Hjøllum, Ian Salter, Anni Djurhuus, Sunnvør í Kongsstovu<p>Biodiversity is under pressure, mainly due to human activities and climate change. At the international policy level, it is now recognised that genetic diversity is an important part of biodiversity. The availability of high-quality reference g...ERGA, ERGA Pilot, Population genomics, VertebratesStephen Richards2023-07-31 16:59:33 View
20 Nov 2023
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Building a Portuguese Coalition for Biodiversity Genomics

The Portuguese genomics community teams up with iconic species to understand the destruction of biodiversity

Recommended by based on reviews by Svein-Ole Mikalsen and 1 anonymous reviewer

This manuscript describes the ongoing work and plans of Biogenome Portugal: a new network of researchers in the Portuguese biodiversity genomics community. The aims of this network are to jointly train scientists in ecology and evolution, generate new knowledge and understanding of Portuguese biodiversity, and better engage with the public and with international researchers, so as to advance conservation efforts in the region. In collaboration across disciplines and institutions, they are also contributing to the European Reference Genome Atlas (ERGA): a massive scientific effort, seeking to eventually produce reference-quality genomes for all species in the European continent (Mc Cartney et al. 2023).

The manuscript centers around six iconic and/or severely threatened species, whose range extends across parts of what is today considered Portuguese territory. Via the Portugal chapter of ERGA (ERGA-Portugal), the researchers will generate high-quality genome sequences from these species. The species are the Iberian hare, the Azores laurel, the Black wheatear, the Portuguese crowberry, the Cave ground beetle and the Iberian minnowcarp. In ignorance of human-made political borders, some of these species also occupy large parts of the rest of the Iberian peninsula, highlighting the importance of transnational collaboration in biodiversity efforts. The researchers extracted samples from members of each of these species, and are building reference genome sequences from them. In some cases, these sequences will also be co-analyzed with additional population genomic data from the same species or genetic data from cohabiting species. The researchers aim to answer a variety of ecological and evolutionary questions using this information, including how genetic diversity is being affected by the destruction of their habitat, and how they are being forced to adapt as a consequence of the climate emergency.

The authors did a very good job in providing a justification for the choice of pilot species, a thorough methodological overview of current work, and well thought-out plans for future analyses once the genome sequences are available for study. The authors also describe plans for networking and training activities to foster a well-connected Portuguese biodiversity genomics community.

Applying a genomic analysis lens is important for understanding the ever faster process of devastation of our natural world. Governments and corporations around the globe are destroying nature at ever larger scales (Diaz et al. 2019). They are also destabilizing the climatic conditions on which life has existed for thousands of years (Trisos et al. 2020). Thus, genetic diversity is decreasing faster than ever in human history, even when it comes to non-threatened species (Exposito-Alonso et al. 2022), and these decreases are disrupting ecological processes worldwide (Richardson et al. 2023). This, in turn, is threatening the conditions on which the stability of our societies rest (Gardner and Bullock 2021). The efforts of Biogenome Portal and ERGA-Portugal will go a long way in helping us understand in greater detail how this process is unfolding in Portuguese territories.

 

 

References

Díaz, Sandra, et al. "Pervasive human-driven decline of life on Earth points to the need for transformative change." Science 366.6471 (2019): eaax3100. https://doi.org/10.1126/science.aax3100

Exposito-Alonso, Moises, et al. "Genetic diversity loss in the Anthropocene." Science 377.6613 (2022): 1431-1435. https://doi.org/10.1126/science.abn5642

Gardner, Charlie J., and James M. Bullock. "In the climate emergency, conservation must become survival ecology." Frontiers in Conservation Science 2 (2021): 659912. https://doi.org/10.3389/fcosc.2021.659912

Mc Cartney, Ann M., et al. "The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics." bioRxiv (2023): 2023-09, ver. 2 peer-reviewed and recommended by Peer Community in Genomics. https://doi.org/10.32942/X20W3Q

Richardson, Katherine, et al. "Earth beyond six of nine planetary boundaries." Science Advances 9.37 (2023): eadh2458. https://doi.org/10.1126/sciadv.adh2458

Trisos, Christopher H., Cory Merow, and Alex L. Pigot. "The projected timing of abrupt ecological disruption from climate change." Nature 580.7804 (2020): 496-501. https://doi.org/10.1038/s41586-020-2189-9

Building a Portuguese Coalition for Biodiversity GenomicsJoão Pedro Marques, Paulo Célio Alves, Isabel R. Amorim, Ricardo J. Lopes, Mónica Moura, Gene Meyers, Manuela Sim-Sim, Carla Sousa-Santos, Maria Judite Alves, Paulo AV Borges, Thomas Brown, Miguel Carneiro, Carlos Carrapato, Luís Ceríaco, Claudio ...<p style="text-align: justify;">The diverse physiography of the Portuguese land and marine territory, spanning from continental Europe to the Atlantic archipelagos, has made it an important repository of biodiversity throughout the Pleistocene gla...ERGA, ERGA PilotFernando Racimo2023-07-14 11:24:22 View
01 May 2024
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Evolution of ion channels in cetaceans: A natural experiment in the tree of life

Positive selection acted upon cetacean ion channels during the aquatic transition

Recommended by ORCID_LOGO based on reviews by 2 anonymous reviewers

The transition of cetaceans (whales, dolphins, and porpoises) from terrestrial to aquatic lifestyles is a striking example of natural selection driving major phenotypic changes (Figure 1). For instance, cetaceans have evolved the ability to withstand high pressure and to store oxygen for long periods, among other adaptations (Das et al. 2023). Many phenotypic changes, such as shifts in organ structure, have been well-characterized through fossils (Thewissen et al. 2009). Although such phenotypic transitions are now well understood, we have only a partial understanding of the underlying genetic mechanisms. Scanning for signatures of adaptation in genes related to phenotypes of interest is one approach to better understand these mechanisms. This was the focus of Uribe and colleagues’ (2024) work, who tested for such signatures across cetacean protein-coding genes.

 

Cetacean fossils

Figure 1: The skeletons of Ambulocetus (an early whale; top) and Pakicetus (the earliest known cetacean, which lived about 50 million years ago; bottom). Copyright: J. G. M. Thewissen. Displayed here with permission from the copyright holder.

 

The authors were specifically interested in investigating the evolution of ion channels, as these proteins play fundamental roles in physiological processes. An important aspect of their work was to develop a bioinformatic pipeline to identify orthologous ion channel genes across a set of genomes. After applying their bioinformatic workflow to 18 mammalian species (including nine cetaceans), they conducted tests to find out whether these genes showed signatures of positive selection in the cetacean lineage. For many ion channel genes, elevated ratios of non-synonymous to synonymous substitution rates were detected (for at least a subset of sites, and not necessarily the entire coding region of the genes). The genes concerned were enriched for several functions, including heart and nervous system-related phenotypes.

One top gene hit among the putatively selected genes was SCN5A, which encodes a sodium channel expressed in the heart. Interestingly, the authors noted a specific amino acid replacement, which is associated with sensitivity to the toxin tetrodotoxin in other lineages. This substitution appears to have occurred in the common ancestor of toothed whales, and then was reversed in the ancestor of bottlenose dolphins. The authors describe known bottlenose dolphin interactions with toxin-producing pufferfish that could result in high tetrodotoxin exposure, and thus perhaps higher selection for tetrodotoxin resistance. Although this observation is intriguing, the authors emphasize it requires experimental confirmation.

The authors also recapitulated the previously described observation (Yim et al. 2014; Huelsmann et al. 2019) that cetaceans have fewer protein-coding genes compared to terrestrial mammals, on average. This signal has previously been hypothesized to partially reflect adaptive gene loss. For example, specific gene loss events likely decreased the risk of developing blood clots while diving (Huelsmann et al. 2019). Uribe and colleagues also considered overall gene turnover rate, which encompasses gene copy number variation across lineages, and found the cetacean gene turnover rate to be three times higher than that of terrestrial mammals. Finally, they found that cetaceans have a higher proportion of ion channel genes (relative to all protein-coding genes in a genome) compared to terrestrial mammals. 

Similar investigations of the relative non-synonymous to synonymous substitution rates across cetacean and terrestrial mammal orthologs have been conducted previously, but these have primarily focused on dolphins as the sole cetacean representative (McGowen et al. 2012; Nery et al. 2013; Sun et al. 2013). These projects have also been conducted across a large proportion of orthologous genes, rather than a subset with a particular function. Performing proteome-wide investigations can be valuable in that they summarize the genome-wide signal, but can suffer from a high multiple testing burden. More generally, investigating a more targeted question, such as the extent of positive selection acting on ion channels in this case, or on genes potentially linked to cetaceans’ increased brain sizes (McGowen et al. 2011) or hypoxia tolerance (Tian et al. 2016), can be easier to interpret, as opposed to summarizing broader signals. However, these smaller-scale studies can also experience a high multiple testing burden, especially as similar tests are conducted across numerous studies, which often is not accounted for (Ioannidis 2005). In addition, integrating signals across the entire genome will ultimately be needed given that many genetic changes undoubtedly underlie cetaceans’ phenotypic diversification. As highlighted by the fact that past genome-wide analyses have produced some differing biological interpretations (McGowen et al. 2012; Nery et al. 2013; Sun et al. 2013), this is not a trivial undertaking. 

Nonetheless, the work performed in this preprint, and in related research, is valuable for (at least) three reasons. First, although it is a challenging task, a better understanding of the genetic basis of cetacean phenotypes could have benefits for many aspects of cetacean biology, including conservation efforts. In addition, the remarkable phenotypic shifts in cetaceans make the question of what genetic mechanisms underlie these changes intrinsically interesting to a wide audience. Last, since the cetacean fossil record is especially well-documented (Thewissen et al. 2009), cetaceans represent an appealing system to validate and further develop statistical methods for inferring adaptation from genetic data. Uribe and colleagues’ (2024) analyses provide useful insights relevant to each of these points, and have generated intriguing hypotheses for further investigation.


References

Das K, Sköld H, Lorenz A, Parmentier E (2023) Who are the marine mammals? In: “Marine Mammals: A Deep Dive into the World of Science”. Brennecke D, Knickmeier K, Pawliczka I, Siebert U, Wahlberg, M (editors). Springer, Cham. p. 1–14. https://doi.org/10.1007/978-3-031-06836-2_1

Huelsmann M, Hecker N, Springer MS, Gatesy J, Sharma V, Hiller M (2019) Genes lost during the transition from land to water in cetaceans highlight genomic changes associated with aquatic adaptations. Science Advances, 5, eaaw6671. https://doi.org/10.1126/sciadv.aaw6671

Ioannidis JPA (2005) Why most published research findings are false. PLOS Medicine, 2, e124. https://doi.org/10.1371/journal.pmed.0020124

McGowen MR, Montgomery SH, Clark C, Gatesy J (2011) Phylogeny and adaptive evolution of the brain-development gene microcephalin (MCPH1) in cetaceans. BMC Evolutionary Biology, 11, 98. https://doi.org/10.1186/1471-2148-11-98

McGowen MR, Grossman LI, Wildman DE (2012) Dolphin genome provides evidence for adaptive evolution of nervous system genes and a molecular rate slowdown. Proceedings of the Royal Society B: Biological Sciences, 279, 3643–3651. https://doi.org/10.1098/rspb.2012.0869

Nery MF, González DJ, Opazo JC (2013) How to make a dolphin: molecular signature of positive selection in cetacean genome. PLOS ONE, 8, e65491. https://doi.org/10.1371/journal.pone.0065491

Sun YB, Zhou WP, Liu HQ, Irwin DM, Shen YY, Zhang YP (2013) Genome-wide scans for candidate genes involved in the aquatic adaptation of dolphins. Genome Biology and Evolution, 5, 130–139. https://doi.org/10.1093/gbe/evs123

Tian R, Wang Z, Niu X, Zhou K, Xu S, Yang G (2016) Evolutionary genetics of hypoxia tolerance in cetaceans during diving. Genome Biology and Evolution, 8, 827–839. https://doi.org/10.1093/gbe/evw037

Thewissen JGM, Cooper LN, George JC, Bajpai  (2009) From land to water: the origin of whales, dolphins, and porpoises. Evolution: Education and Outreach, 2, 272–288. https://doi.org/10.1007/s12052-009-0135-2

Uribe C, Nery M, Zavala K, Mardones G, Riadi G, Opazo J (2024) Evolution of ion channels in cetaceans: A natural experiment in the tree of life. bioRxiv, ver. 8 peer-reviewed and recommended by Peer Community in Genomics. https://doi.org/10.1101/2023.06.15.545160

Yim HS, Cho YS, Guang X, Kang SG, Jeong JY, Cha SS, Oh HM, Lee JH, Yang EC, Kwon KK, et al. (2014) Minke whale genome and aquatic adaptation in cetaceans. Nature Genetics, 46, 88–92. https://doi.org/10.1038/ng.2835

 

Evolution of ion channels in cetaceans: A natural experiment in the tree of lifeCristóbal Uribe, Mariana F. Nery, Kattina Zavala, Gonzalo A. Mardones, Gonzalo Riadi & Juan C. Opazo<p>Cetaceans could be seen as a natural experiment within the tree of life in which a mammalian lineage changed from terrestrial to aquatic habitats. This shift involved extensive phenotypic modifications, which represent an opportunity to explore...Evolutionary genomicsGavin Douglas2023-07-04 20:53:46 View
01 Jul 2024
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Contextualising samples: Supporting reference genomes of European biodiversity through sample and associated metadata collection

To avoid biases and to be FAIR, we need to CARE and share biodiversity metadata

Recommended by ORCID_LOGO based on reviews by Julian Osuji and 1 anonymous reviewer

Böhne et al. (2024) do not present a classical scientific paper per se but a report on how the European Reference Genome Atlas (ERGA) aims to deal with sampling and sample information, i.e. metadata.

As the goal of ERGA is to provide an almost fully representative set of reference genomes representative of European biodiversity to serve many research areas in biology, they have to be really exhaustive. In this regard, in addition to providing sample metadata recording guidelines, they also discuss the biases existing in sampling and sequencing projects.

The first task for such a project is to be sure that the data they generate will be usable and available in the future (“[in] perpetuity", Böhne et al. 2024). The authors deployed a very efficient pipeline for conserving information on sampling: location, physical information, copies of tissues and of DNA, shipping, legal/ethical aspects regarding the Nagoya Protocol, etc., alongside a best-practice manual. This effort is linked to practical guides for the DNA extraction of specific taxa. More generally, these details enable “Findable, Accessible, Interoperable, and Reusable” (FAIR) principles (Wilkinson et al. 2016) to be followed.

An important aspect of this paper, in addition to practical points, is the reflection upon the different biases inherent to the choice of sequenced samples. Acknowledging their own biases with regards to DNA extraction protocol efficiency, small genome size choice, as well as the availability of material (Nagoya Protocol aspects) and material transfer efficiency, the authors recommend in the future to not survey biodiversity by selecting one’s favorite samples or species, but also considering "orphan" taxa. Some of these "orphan" taxonomic groups belong to non-arthropod invertebrates but internal disparities are also prominent within other taxa. Finally, the implementation of the "Collective benefit, Authority to control, Responsibility, and Ethics" (CARE) principles (Carroll et al. 2021) will allow Indigenous rights to be considered when prioritizing samples, and to enable their "knowledge systems to permeate throughout the process of reference genome production and beyond" (Böhne et al. 2024).

Last, but not least, as ERGA, including its Sampling and Sample Processing committee, is a large collective effort, it is very refreshing to read a paper starting with the acknowledgements and the roles of each member.

                               

References

Böhne A, Fernández R, Leonard JA, McCartney AM, McTaggart S, Melo-Ferreira J, Monteiro R, Oomen RA, Pettersson OV, Struck TH (2024) Contextualising samples: Supporting reference genomes of European biodiversity through sample and associated metadata collection. bioRxiv, ver. 3 peer-reviewed and recommended by Peer Community in Genomics. https://doi.org/10.1101/2023.06.28.546652

Carroll SR, Herczog E, Hudson M, Russell K, Stall S (2021) Operationalizing the CARE and FAIR Principles for Indigenous data futures. Scientific Data, 8, 108. https://doi.org/10.1038/s41597-021-00892-0

Wilkinson MD, Dumontier M, Aalbersberg IjJ, Appleton G, Axton M, Baak A, Blomberg N, Boiten J-W, da Silva Santos LB, Bourne PE, Bouwman J, Brookes AJ, Clark T, Crosas M, Dillo I, Dumon O, Edmunds S, Evelo CT, Finkers R, Gonzalez-Beltran A, Gray AJG, Groth P, Goble C, Grethe JS, Heringa J, ’t Hoen PAC, Hooft R, Kuhn T, Kok R, Kok J, Lusher SJ, Martone ME, Mons A, Packer AL, Persson B, Rocca-Serra P, Roos M, van Schaik R, Sansone S-A, Schultes E, Sengstag T, Slater T, Strawn G, Swertz MA, Thompson M, van der Lei J, van Mulligen E, Velterop J, Waagmeester A, Wittenburg P, Wolstencroft K, Zhao J, Mons B (2016) The FAIR Guiding Principles for scientific data management and stewardship. Scientific Data, 3, 160018. https://doi.org/10.1038/sdata.2016.18

Contextualising samples: Supporting reference genomes of European biodiversity through sample and associated metadata collectionAstrid Böhne, Rosa Fernández, Jennifer A. Leonard, Ann M. McCartney, Seanna McTaggart, José Melo-Ferreira, Rita Monteiro, Rebekah A. Oomen, Olga Vinnere Pettersson, Torsten H. Struck<p>The European Reference Genome Atlas (ERGA) consortium aims to generate a reference genome catalogue for all of Europe's eukaryotic biodiversity. The biological material underlying this mission, the specimens and their derived samples, are provi...ERGA, ERGA BGE, ERGA Pilot, Evolutionary genomicsFrancois Sabot Julian Osuji, Francois Sabot, Anonymous2023-07-03 10:39:36 View
15 Jan 2024
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The genome sequence of the Montseny horsehair worm, Gordionus montsenyensis sp. nov., a key resource to investigate Ecdysozoa evolution

Embarking on a novel journey in Metazoa evolution through the pioneering sequencing of a key underrepresented lineage

Recommended by ORCID_LOGO based on reviews by Gonzalo Riadi and 2 anonymous reviewers

Whole genome sequences are revolutionizing our understanding across various biological fields. They not only shed light on the evolution of genetic material but also uncover the genetic basis of phenotypic diversity. The sequencing of underrepresented lineages, such as the one presented in this study, is of critical importance. It is crucial in filling significant gaps in our understanding of Metazoa evolution. Despite the wealth of genome sequences in public databases, it is crucial to acknowledge that some lineages across the Tree of Life are underrepresented or absent. This research represents a significant step towards addressing this imbalance, contributing to the collective knowledge of the global scientific community.

In this genome note, as part of the European Reference Genome Atlas pilot effort to generate reference genomes for European biodiversity (Mc Cartney et al. 2023), Klara Eleftheriadi and colleagues (Eleftheriadi et al. 2023) make a significant effort to add a genome sequence of an unrepresented group in the animal Tree of Life. More specifically, they present a taxonomic description and chromosome-level genome assembly of a newly described species of horsehair worm (Gordionus montsenyensis). Their sequence methodology gave rise to an assembly of 396 scaffolds totaling 288 Mb, with an N50 value of 64.4 Mb, where 97% of this assembly is grouped into five pseudochromosomes. The nuclear genome annotation predicted 10,320 protein-coding genes, and they also assembled the circular mitochondrial genome into a 15-kilobase sequence.

The selection of a species representing the phylum Nematomorpha, a group of parasitic organisms belonging to the Ecdysozoa lineage, is good, since today, there is only one publicly available genome for this animal phylum (Cunha et al. 2023). Interestingly, this article shows, among other things, that the species analyzed has lost ∼30% of the universal Metazoan genes. Efforts, like the one performed by Eleftheriadi and colleagues, are necessary to gain more insights, for example, on the evolution of this massive gene lost in this group of animals.


References

Cunha, T. J., de Medeiros, B. A. S, Lord, A., Sørensen, M. V., and Giribet, G. (2023). Rampant Loss of Universal Metazoan Genes Revealed by a Chromosome-Level Genome Assembly of the Parasitic Nematomorpha. Current Biology, 33 (16): 3514–21.e4. https://doi.org/10.1016/j.cub.2023.07.003

Eleftheriadi, K., Guiglielmoni, N., Salces-Ortiz, J., Vargas-Chavez, C., Martínez-Redondo, G. I., Gut, M., Flot, J.-F., Schmidt-Rhaesa, A., and Fernández, R. (2023). The Genome Sequence of the Montseny Horsehair worm, Gordionus montsenyensis sp. Nov., a Key Resource to Investigate Ecdysozoa Evolution. bioRxiv, ver. 3 peer-reviewed and recommended by Peer Community in Genomics. https://doi.org/10.1101/2023.06.26.546503

Mc Cartney, A. M., Formenti, G., Mouton, A., De Panis, D., Marins, L. S., Leitão, H. G., Diedericks, G., et al. (2023). The European Reference Genome Atlas: Piloting a Decentralised Approach to Equitable Biodiversity Genomics. bioRxiv. https://doi.org/10.1101/2023.09.25.559365

The genome sequence of the Montseny horsehair worm, *Gordionus montsenyensis* sp. nov., a key resource to investigate Ecdysozoa evolutionEleftheriadi Klara, Guiglielmoni Nadège, Salces-Ortiz Judit, Vargas-Chávez Carlos, Martínez-Redondo Gemma I, Gut Marta, Flot Jean François, Schmidt-Rhaesa Andreas, Fernández Rosa<p>Nematomorpha, also known as Gordiacea or Gordian worms, are a phylum of parasitic organisms that belong to the Ecdysozoa, a clade of invertebrate animals characterized by molting. They are one of the less scientifically studied animal phyla, an...ERGA PilotJuan C. Opazo2023-06-29 10:31:36 View
07 Sep 2023
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The demographic history of the wild crop relative Brachypodium distachyon is shaped by distinct past and present ecological niches

Natural variation and adaptation in Brachypodium distachyon

Recommended by based on reviews by Thibault Leroy and 1 anonymous reviewer

Identifying the genetic factors that allow plant adaptation is a major scientific question that is particularly relevant in the face of the climate change that we are already experiencing. To address this, it is essential to have genetic information on a high number of accessions (i.e., plants registered with unique accession numbers) growing under contrasting environmental conditions. There is already an important number of studies addressing these issues in the plant Arabidopsis thaliana, but there is a need to expand these analyses to species that play key roles in wild ecosystems and are close to very relevant crops, as is the case of grasses.

The work of Minadakis, Roulin and co-workers (1) presents a Brachypodium distachyon panel of 332 fully sequences accessions that covers the whole species distribution across a wide range of bioclimatic conditions, which will be an invaluable tool to fill this gap. In addition, the authors use this data to start analyzing the population structure and demographic history of this plant, suggesting that the species experienced a shift of its distribution following the Last Glacial Maximum, which may have forced the species into new habitats. The authors also present a modeling of the niches occupied by B. distachyon together with an analysis of the genetic clades found in each of them, and start analyzing the different adaptive loci that may have allowed the species’ expansion into different bioclimatic areas.

In addition to the importance of the resources made available by the authors for the scientific community, the analyses presented are well done and carefully discussed, and they highlight the potential of these new resources to investigate the genetic bases of plant adaptation. 

References

1. Nikolaos Minadakis, Hefin Williams, Robert Horvath, Danka Caković, Christoph Stritt, Michael Thieme, Yann Bourgeois, Anne C. Roulin. The demographic history of the wild crop relative Brachypodium distachyon is shaped by distinct past and present ecological niches. bioRxiv, 2023.06.01.543285, ver. 5 peer-reviewed and recommended by Peer Community in Genomics. https://doi.org/10.1101/2023.06.01.543285

The demographic history of the wild crop relative *Brachypodium distachyon* is shaped by distinct past and present ecological nichesNikolaos Minadakis, Hefin Williams, Robert Horvath, Danka Caković, Christoph Stritt, Michael Thieme, Yann Bourgeois, Anne C. Roulin<p style="text-align: justify;">Closely related to economically important crops, the grass <em>Brachypodium distachyon</em> has been originally established as a pivotal species for grass genomics but more recently flourished as a model for develop...Evolutionary genomics, Functional genomics, Plants, Population genomicsJosep Casacuberta2023-06-14 15:28:30 View
06 Aug 2024
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Identification and quantification of transposable element transcripts using Long-Read RNA-seq in Drosophila germline tissues

Unveiling transposon dynamics: Advancing TE expression analysis in Drosophila with long-read sequencing

Recommended by based on reviews by Silke Jensen, Christophe Antoniewski and 1 anonymous reviewer

Transposable elements (TEs) are mobile genetic elements with an intrinsic mutagenic potential that influences the physiology of any cell type, whether somatic or germinal. Measuring TE expression is a fundamental prerequisite for analysing the processes leading to the activity of TE-derived sequences. This applies to both old and recent TEs, as even if they are deficient in mobilisation, transcription of TE sequences alone can impact neighbouring gene expression and other cellular activities.

In terms of TE physiology, transcription is crucial for mobilisation activity. The transcription of some TEs can be tissue-specific and associated with splicing events, as exemplified by the P-element isoforms in the fruit fly (Laski et al. 1986). Regarding host cell physiology, TE transcripts can include nearby exons, with or without splicing, and such chimeric transcripts can significantly alter gene activity. Thus, quantitative and qualitative analyses must be conducted to assess TE function and how they can modify genomic activities. Yet, due to the polymorphic, interspersed, and repetitive nature of TE sequences, the quantitative and qualitative analysis of TE transcript levels using short-read sequencing remains challenging (Lanciano and Cristofari 2020).

In this context, Rebollo et al. (2024) employed nanopore long-read sequencing to analyse cDNAs derived from Drosophila melanogaster germline RNAs. The authors constructed two long-read cDNA libraries from pooled ovaries and testes using a protocol to obtain full-length cDNAs and sequenced them separately. They carefully compared their results with their short-read datasets. Overall, their observations corroborate known patterns of germline-specific expression of certain TEs and provide initial evidence of novel spliced TE transcript isoforms in Drosophila.

Rebollo and colleagues have provided a well-documented and detailed analysis of their results, which will undoubtedly benefit the scientific community. They presented the challenges and limitations of their approach, such as the length of the transcripts, and provided a reproducible analysis workflow that will enable better characterisation of TE expression using long-read technology.

Despite the small number of samples and limited sequencing depth, this pioneering study strikingly demonstrates the potential of long-read sequencing for the quantitative and qualitative analysis of TE transcription, a technology that will facilitate a better understanding of the transposon landscape.

              
References

Lanciano S, Cristofari G (2020) Measuring and interpreting transposable element expression. Nature Reviews Genetics, 21, 721–736. https://doi.org/10.1038/s41576-020-0251-y

Laski FA, Rio DC, Rubin GM (1986) Tissue specificity of Drosophila P element transposition is regulated at the level of mRNA splicing. Cell, 44, 7–19. https://doi.org/10.1016/0092-8674(86)90480-0

Rebollo R, Gerenton P, Cumunel E, Mary A, Sabot F, Burlet N, Gillet B, Hughes S, Oliveira DS, Goubert C, Fablet M, Vieira C, Lacroix V (2024) Identification and quantification of transposable element transcripts using Long-Read RNA-seq in Drosophila germline tissues. bioRxiv, ver.4 peer-reviewed and recommended by PCI Genomics. https://doi.org/10.1101/2023.05.27.542554

Identification and quantification of transposable element transcripts using Long-Read RNA-seq in Drosophila germline tissuesRita Rebollo, Pierre Gerenton, Eric Cumunel, Arnaud Mary, François Sabot, Nelly Burlet, Benjamin Gillet, Sandrine Hughes, Daniel Siqueira Oliveira, Clément Goubert, Marie Fablet, Cristina Vieira, Vincent Lacroix<p>Transposable elements (TEs) are repeated DNA sequences potentially able to move throughout the genome. In addition to their inherent mutagenic effects, TEs can disrupt nearby genes by donating their intrinsic regulatory sequences, for instance,...Arthropods, Bioinformatics, Viruses and transposable elementsNicolas Pollet2023-06-13 14:46:20 View