The somatic mutation landscape of the human body

In this paper, scientists used transcriptome data from over 7,500 tissue samples and 36 tissue types to create a catalog of human somatic mutations. Their catalog contains over 280,000 mutations in total and illustrates a number of tissue-specific mutations.

"Tissues that have more mutations than expected from sequencing depth include those most often exposed to environmental mutagens or with a high cellular turnover like the skin, lung, blood, esophagus mucosa, spleen, liver, and small intestine (Fig. 2a). On the other end of the spectrum are those with low environmental exposure or low cellular turnover such as the brain, adrenal gland, prostate, and several types of muscle—heart, esophagus muscularis, and skeletal muscle."

They also found age was correlated with mutation levels across most tissues. Blood showed the highest association with age and sun-exposed skin had the most significant association with C>T mutations commonly associated with UV radiation. They also found higher levels of mutations in female breast tissue compared to men.

Importantly, they also observed that cancer mutations are enriched in non-diseased tissues, which leads them to say these genes are evolving under positive selection and these mutations increased cellular proliferation even before cancer is observed.

Zac Truesdell - Journal update - Genome Biology - 5
https://genomebiology.biomedcentral.com/articles/10.1186/s13059-019-1919-5

The Deep Genome Project

Mice are often used as an organism to study human disease, due to the high number of orthologous genes. Genomic studies over the decades have been able to computationally predict and annotate a large number of genes. However, according to the authors, "more than 75 to 80% of the computationally annotated ~ 20,000 genes in the human genome have not had variation in them tied to any specific phenotype."

To fill in this gap between genotype and phenotype, the authors call for the establishment of an ambitious "Deep Genome Project" to sort of be the spiritual successor to the Human Genome Project (which, as we learned in class, still left a lot of biological questions unanswered).

"The implementation of a Deep Genome Project—to deliver the functional biological annotation of all human orthologous genomic elements in mice—is an essential and executable strategy to transform our understanding of genetic and genomic variation in human health and disease that will catalyze delivery of the promised benefits of genomic medicine to children and adults around the world."

Zac Truesdell - Journal update - Genome Biology - 4
https://genomebiology.biomedcentral.com/articles/10.1186/s13059-020-1931-9

Longitudinal survey of microbiome associated with particulate matter in a megacity

Smog and particulate matter in the air can have major health impacts. Often, we only think about how the chemical compounds of air pollution effect us, but particulate matter also serves as an environment for bacteria to thrive. This study examines the composition of the airborne bacterial community in Beijing over a 6 month period.

Overall, the bacterial community was relatively similar at both high and low particulate matter size. However, it seems that when the air is heavily polluted, larger particulate matter allows for higher levels of bacteria. If I'm understanding the paper correctly, basically the larger particulate matter sizes give more surface area for the bacteria, and also allow interactions between the bacteria species, such as horizontal gene transfer.

So, next time you take a breath of fresh city air, remember it has bacteria from human, dog, and mouse feces floating around in it.

Zac Truesdell - Journal update - Genome Biology - 3
https://genomebiology.biomedcentral.com/articles/10.1186/s13059-020-01964-x

Functional consequences of archaic introgression and their impact on fitness

In this paper, the authors discuss the positive and negative effects on fitness caused by admixture with Neanderthals and Denisovans.

The lower frequency of archaic ancestry on the X chromosome and near testis-expressed genes suggests that first-generation hybrids had high levels of infertility. Additionally, loci associated with neurological and psychiatric disorders have higher levels of archaic haplotypes, suggesting deleterious effects of archaic admixture.

Some results of archaic admixture were positive--including genes associated with skin pigmentation and metabolism. These alleles would have allowed ancient humans to adapt to different climatic regions more rapidly. Some Neanderthal alleles related to immune function have also led to positive adaptations in humans.

Zac Truesdell - Journal update - Genome Biology - 2
https://genomebiology.biomedcentral.com/articles/10.1186/s13059-019-1920-z

CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma

I think I forgot to post a potluck article during the CRISPR discussion week, so here is something interesting.

Long non-coding RNAs (lncRNA) have highly-specific expression in different cell types, giving them potential to be used for targeting specific types of cancer. However, very few lncRNAs have been studied or tested for these purposes yet.

Researchers in this paper used CRISPR interference to screen lncRNA loci on human glioblastoma cells. In class we talked about how CRISPR can be used to edit genomes, but it seems it can also be used to screen for gene function.

Through this method, they identified a number of lncRNA Glioma Radiation Sensitizers (lncGRS). Targeting of lncGRS inhibit growth of glioma cells (brain tumors), but not normal brain cells.



Zac Truesdell - CRISPR potluck/Journal update - Genome Biology

https://genomebiology.biomedcentral.com/articles/10.1186/s13059-020-01995-4

Journal Update 3: The Fabry disease-causing mutation, GLA IVS4+919G>A, originated in Mainland China more than 800 years ago

Throughout Southeast Asia, GLA IVS4+919G>A mutation is found in high prevalence in patients with hypertrophic cardiomyopathy. This x-linked mutation is the cause of Fabry disease. Liang and others sampled 33 male patients with the mutation from throughout Southeast Asia to identify its age and origins. The mutation was found to be associated with a specific haplotype, not shared by 15 healthy people. Based on this finding, they suggest that there was a single founder for the GLA IVS4 mutation. They estimated the age of the haplotype using linkage-disequilibrium decay theory and found an estimated date between 800 and a 1000 years ago.

Joshua Porter – Journal of Human Genetics Update 3

https://www.nature.com/articles/s10038-020-0745-7

Journal Update 2: Y-chromosome evidence confirmed the Kerei-Abakh origin of Aksay Kazakhs

Genetic diversity outside of Europe has historically been neglected. As sequencing costs decrease, more and more researchers are sampling new populations outside of Europe. Recent work by Wen et al. tested 93 Aksay Kazakh men. These Kazakhs reside in China and are located along the former Silk Road. Their study focused on 106 bialllic markers and 17 short tandem repeats (STRs) of the Y-chromosome. Wen and others found low levels of haplogroup diversity, suggesting limited paternal admixture. They suggest this is related to a tendency to migrate in clans. They also theorize that the Aksay Kazakhs originate from the Kerei-Abakh clan of Kazakhstan and migrated between 1000-1400 years ago. Further studies of under sampled populations will allow researchers to develop higher resolution understandings of the past.

Joshua Porter – Journal of Human Genetics Update 2

https://www.nature.com/articles/s10038-020-0759-1

Journal Update 4: An atlas of the protein-coding genes in the human, pig, and mouse brain

This paper aimed to create an atlas illustrating the spatial expression of transcripts and proteins across cells, tissues, and organs in the brain in humans, mice, and pigs. The rationale was that a broader comparative perspective would lead to better insight into neurobiology and associated diseases. 

As might be expected, the broader organizational patterns were conserved between the mammalian species. However, there was greater variability at the finer level, such as differences between neurotransmitter receptors. Specifically, human-mouse neurotransmitter receptors were significantly more different than human-pig, potentially illustrating that mice may not always be the best clinical test for human brain studies. This study's results also show support for linked function between many genes in microglia and immune cells. Additionally, genes previously thought to be exclusive to astrocytes were shown to be linked to skeletal muscle and liver development. This OPEN ACCESS data can allow other research to take advantage of this broadly sweeping study potentially leading to clinical and research related advances in a variety of disciplines. 


Sjöstedt E, Zhong W, Fagerberg L, Karlsson M, Mitsios N, Adori C, Oksvold P, Edfors F, Limiszewska A, Hikmet F, Huang J. An atlas of the protein-coding genes in the human, pig, and mouse brain. Science. 2020 Mar 6;367(6482).

Ryan McRae
Science

Journal Update 3: CRISPR-engineered T cells in patients with refractory cancer

CRISPR provides a powerful tool to modify genes to treat a variety of illnesses. This paper presents the first human trials to use CRISPR edited t-cells to fight cancer. Specifically, the team deleted two genes (TRAC, TRBC) to reduce misparing of t-cell receptors and to enhance the synthetic, cancer specific transgene (NY-ESO-1). The team also removed a third gene (PDCD1) to improve anti-tumor immunity. While the study was not aiming to treat cancer, it did show the viability for using this method to treat future patients. Using three patients with refractory cancer, they showed that modified t-cells persisted for up to nine months, providing the framework for potential future therapy. 

Stadtmauer EA, Fraietta JA, Davis MM, Cohen AD, Weber KL, Lancaster E, Mangan PA, Kulikovskaya I, Gupta M, Chen F, Tian L. CRISPR-engineered T cells in patients with refractory cancer. Science. 2020 Feb 28;367(6481).

Ryan McRae
Science

Journal Update 2: Genetics of schizophrenia in the South African Xhosa

Schizophrenia is a neurodegenerative disease that often leads to whatever genetic mutations causing it not to passed on to new generations. Thus, it is highly genetically heterogeneous and caused by a variety of de novo mutations. This study aimed to fill a major knowledge gap in schizophrenia research by studying the Xhosa of South Africa, not because they have a high prevalence of schizophrenia, but because most studies have focused on European and Asian populations. Africa has the greatest genetic diversity among modern humans, so new insights could be particularly likely studying African populations. 

Using over 900 control and over 900 individuals with Schizophrenia, this study looked at how specific genes altered the synaptic pathways in different manners, leading to schizophrenia (image below)

Comparing results with a study of Swedish participants, they found that disruptions in synaptic signaling and synaptic plasticity in particular were critical to the development of schizophrenia. This is important as since the higher genetic diversity of African populations leads to more confident gene-phenotype matching, these results can be used to help diagnose and treat schizophrenia in other populations. 


Gulsuner S, Stein DJ, Susser ES, Sibeko G, Pretorius A, Walsh T, Majara L, Mndini MM, Mqulwana SG, Ntola OA, Casadei S. Genetics of schizophrenia in the South African Xhosa. Science. 2020 Jan 31;367(6477):569-73.

Ryan McRae
Science

Journal Update 1: Gene expression regulated by RNA stability

By now it is easily accepted and widely known that a variety of factors go into how the actual coding portion of the genome is transcripted and translated into a final protein end product. This article by Shoshani and Cleveland succinctly outlines how one such factor, mRNA stability, can contribute to gene expression. The autoregulation of tubulin is such that the production of more tubulin is regulated by the concentration of tubulin already present (hence, the autoregulation: tubulin regulates its own production). A portion of the tubulin protein (TTC5 in image) binds to a receptor site on the tRNA which causes the mRNA being translated to degrade, maintaining tubulin concentrations. The discovery of exactly how this mechanism functions can lead to new insights on cell biology and cell self-regulation.

Shoshani O, Cleveland DW. Gene expression regulated by RNA stability. Science. 2020 Jan 3;367(6473):29-.

Ryan McRae
Science

Genome-wide SNP typing of ancient DNA: Determination of hair and eye color of Bronze Age humans from their skeletal remains

Genome-wide SNP typing of ancient DNA: Determination of hair and eye color of Bronze Age humans from their skeletal remains 

This paper used SNP typing method to determine hair and eye color using ancient and degraded DNA. SNPs are good markers when studying phenotypes. This method would be beneficial in forensics, requiring only a minimal amount of DNA (ex. unknown persons involved in water or fire damage). This study looked at a prehistoric European population to determine hair and eye colors of 59 individuals. The remains date back to the Bronze Age (~3,000 years old), and extracted DNA from teeth, petrosal bone, femurs, and tibias with excellent preservation (even full STR typing). They were able to identify hair and eye color for 38 out of 59 individuals. While there were some issues (deviating results, allelic dropouts), this method shows that with some alternations, like increasing DNA in amplification, that this could be a beneficial method for studying phenotypic traits of an entire prehistoric population. 

I linked the article since the charts encompass several pages with the results of probable hair and eye colors.

Kailie Batsche

AJPA Journal Update May 2020

Authors: Nicole Schmidt, Katharina Schücker, Michael Klintschar, Susanne Hummel

Link: https://onlinelibrary.wiley.com/doi/full/10.1002/ajpa.23996

Historical human remains identification through maternal and paternal genetic signatures in a founder population with extensive genealogical record

Historical human remains identification through maternal and paternal genetic signatures in a founder population with extensive genealogical record

This paper introduced a method of identifying human remains from unmarked graves in Québec. They used BALSAC database to look at lineage markers (aDNA and modern) to identify candidate sons that the remains could have originated. This method relied on (1) mtDNA and Y-chromosome haplotype comparison within BALSAC, (2) matching the haplotypes of contemporary individuals, and (3) males that share the same combination of Y-chromosome and mtDNA haplotypes as the exhumed individuals. They used the remains of six male individuals (teeth and petrous bones) to conduct this study. Out of 30, only six were able to provide enough DNA to replicate. This method is interesting, due to the use of genealogical data available. They also brought up how immigrant men were not able to be identified since the maternal signature was unknown. They were able to identify several candidates that matched one specimen, showing that this does have potential with more in-depth genealogical and genetic data down the road.

Kailie Batsche

AJPA Journal Update April 2020

Authors: Tommy Harding, Jean-Francois Lefebvre, Jean-Sébastien Bournival, Hélène Vézina, Emmanuel Milot, Claudia Moreau, Catherine Laprise, Ferran Casals, Isabelle Ribot, Damian Labuda

Link: https://onlinelibrary.wiley.com/doi/abs/10.1002/ajpa.24024

Journal Update 4: Contrasting genomic and phenotypic outcomes of hybridization between pairs of mimetic butterfly taxa across a suture zone

In this study, researchers use reduced-complexity genomic data to compare phenotypes, genetic structure and hybridization patterns of two mimetic butterfly species, Ithomia salapia and Oleria onega. Müllerian mimicry in butterflies describes a defense mechanism where multiple species converge locally on warning wing colour patterns and form mimicry “rings”. Since nonmimetic butterflies can go through more intense selective pressure due to predation risk, mimicry can be seen as a strong ecological driver of speciation and could potentially have triggered the diversification of large radiations of mimetic butterflies.
 

Using a genotyping by sequence approach to generate genetic data and analyzing over 30000 SNPs, the researchers finds that there are significant genotypic as well as phenotypic difference between the 2 species. For the 2 I. salapia lineages analyzed,  the results show that they seem to hybridize only rarely (shown as a in figure above). On the other hand, hybrids are not only more commonly found in O. onega, they are also genetically and phenotypically more variable (shown as b).  

Admixture mapping analysis shows that a small percentage of SNPs analyzed are associated with colour pattern variation in I. salapia (0.49%) and in O. onega ( 0.69%). However, these loci are normally represented among the candidate barrier loci. The researchers suggest that this result might imply other genetic mechanisms could play an important role in the hybridization and and variations observed. 

Gauthier, J., de Silva, D.L., Gompert, Z., Whibley, A., Houssin, C., Le Poul, Y., McClure, M., Lemaitre, C., Legeai, F., Mallet, J. and Elias, M., 2020. Contrasting genomic and phenotypic outcomes of hybridization between pairs of mimetic butterfly taxa across a suture zone. Molecular Ecology.

Molecular Ecology

Monica Cheung– April 29, 2020

Journal Update 3: Complex patterns of differentiation and gene flow underly the divergence of aposematic phenotypes in Oophaga poison frogs

O. anchicayensis (a), O. lehmanni (c), and a putative hybrid poison frog (b)

Hybridization between divergent populations or species can provide important insight to evolution and speciation of populations. In this paper, the researchers stress on the importance of understanding genetic diversity and biological speciation process, and how this knowledge is useful in developing genetic conservation strategies. Using trait data, reduced‐representation genome sequences, and statistical population genomics, Ebersbach et al. look at the evolutionary outcomes and conservation implications of hybridization between critically endangered O. lehmanni its sister taxon, O. anchicayensis. 

Population genomics analysis shows that hybridization between O. lehmanni and O. anchicayensis gave rise to a completely new species with different colour pattern (shown as b in image above). The results suggest that the novel colour pattern phenotypes follow a mosaic evolutionary pattern, inherited from O. lehmanni and O. anchicayensis. Results from historical demographic inferences also suggest that this observation is more likely to have originated from long-term isolation of populations rather than recent human interference to their habitats due to pet trades. The researchers conclude that this case study shows that divergence via admixture as an evolutionary process might be more common than previously thought in nature.

Current conservation efforts focus mostly on established species and lack guidelines from hybrid species. Since this research shows that hybridization can be more common than previously known, population genomics studies on hybrid species can help policy administrators to better understand hybrid species and develop more appropriate conservation strategies. 

Ebersbach, J., Posso‐Terranova, A., Bogdanowicz, S., Gómez‐Díaz, M., García‐González, M.X., Bolívar‐García, W. and Andrés, J., 2020. Complex patterns of differentiation and gene flow underly the divergence of aposematic phenotypes in Oophaga poison frogs. Molecular Ecology.

Molecular Ecology Journal Update

Monica Cheung– April 27, 2020

Journal Update 2: Population genetics of fruit bat reservoir informs the dynamics, distribution and diversity of Nipah virus

The recent outbreak of covid-19 calls major attention to the threats that zoonotic diseases can pose to human as a species. Out of many hosts and vectors for zoonoses, bats are exceptionally notorious for its ability to transmit diseases to human. This is mainly due to the bat's complex immune system, allowing the mammal to carry pathogens without being affected. This research by Olival et al. focuses on the distribution and mechanisms of Nipah virus, through studying the population genetics of fruit bats. 

Nipah virus is a fatal zoonotic RNA paramyxovirus (genus Henipavirus) with bats being its main reservoir host. Depending on the strain, it can have a fatality rate of 40-70% and it has been causing reported deaths continuously since 2001.The goal of this study is to gain better understanding on host population genetic structure in order to improve models of viral circulation dynamics. 

Using mitochondrial DNA and nuclear microsatellite markers, the authors were able to measure population structure, demographic history and phylogeography of P. medius in Bangladesh.They also performed a phylogeographic analysis on all known Nipah virus sequences and strains in order to investigate the virus’ evolutionary history. 

The results show that P. medius experienced both genetic and morphological differentiation between 2 populations in eastern Bangladesh, producing divergent strains of Nipah virus. The graph above shows that there are several clades of NiV identified in this study. “NiV clades I and II are cocirculating among several Pteropus species (and other bat genera) across South and South‐East Asia, suggesting that NiV is characterized by weak host specificity.” These two NiV clades are shared in P. lylei populations in central Thailand, while only clade II (NiV‐MY) has been found in P. vampyrus and P. hypomelanus. This discovery helps to identify the specific strains with their original hosts, and can be useful to public health measures as different genotypes of NiV can have different clinical presentations in humans and animals. 

Demographic analysis also shows that a large population of Pteropus species has existed in Bangladesh since the late Plesitocene, coinciding with the first hominin expansion. This suggests that Nipah virus spillover to human might have a longer history than previously expected. 

Olival, K.J., Latinne, A., Islam, A., Epstein, J.H., Hersch, R., Engstrand, R.C., Gurley, E.S., Amato, G., Luby, S.P. and Daszak, P., 2020. Population genetics of fruit bat reservoir informs the dynamics, distribution and diversity of Nipah virus. Molecular Ecology, 29(5), pp.970-985.

Molecular Ecology Journal Update

Monica Cheung– April 23, 2020

Journal Update 4: Wild chimpanzees exhibit human-like aging of glucocorticoid regulation

This article by Thompson et al. presents the results of a study on urinary cortisol levels in 59 wild chimpanzees from Uganda. Glucocorticoids are produced by the body in response to stressors, but eventually has long-term effects on several of the body's systems associated with aging. This study found that wild chimp cortisol levels varied due to factors such as age, rank (in males), and reproductive state (in females). Most importantly, their findings seem to show that patterns of aging in the hypothalamus-pituitary-adrenal axis associated with increased corticoid production appear to be shared between chimps and humans, suggesting that this aspect of aging in humans is not the result of a long lifespan or the modern human environment, but may have come from a common ancestor.

Audrey Tjahjadi

Link to original article: https://www.pnas.org/content/pnas/117/15/8424.full.pdf

Journal Update 3: Using CRISPR to silence lncRNA

Long non-coding RNAs are RNA molecules that are not thought to code for proteins. However, lcRNAs are thought to play a role in regulation of gene expression. An earlier study has identified the use of CRISPR to silence lcRNAs to potentially allow for expression of the gene or increased protein production. This article details how a form of CRISPR called CRISPR interference (CRISPRi) can be used to prevent transcription rather than cause a break in the DNA. In particular, this technology could be useful in the treatment of lymphomas.

Audrey Tjahjadi

Link to commentary about article: https://www.pnas.org/content/117/15/8225?etoc=#ref-7

Week 8: Genetics of neocortical expansion Potluck - Lab Dishes Up Mini-Brains

This article from Science talks about cerebral organoids which are “mini-brains” no larger than an apple seed. These cerebral organoids are grown from human embryonic stem cells of semi organized knots of neural tissue that contain the rudiments of key parts of the human brain, i.e. the hippocampus and prefrontal cortex. Cerebral organoids have structures that are similar to the choroid plexus, the cerebral cortex, and the retinal tissue but do not have any blood vessels so their cells at their core dies. After about 16 days the organoid develops what appears to be the forebrain, midbrain and hind brain. As of right now they are not good models for studying complex neurodevelopmental orders like autism or schizophrenia because those cells involve more complex connections and mature cells. However, what they are good for is understanding how cells switch from proliferation to differentiation. 

Warrenkevin Henderson

Brain Potluck

https://science.sciencemag.org/content/341/6149/946/tab-pdf

Journal Update 1: Absence of founder effect and evidence for adaptive divergence in a recently introduced insular population of white‐tailed deer

In this research paper, the authors study the scenario where a small population of white-tailed deer (Odocoileus virginianus) was introduced to an island from the mainland. About 120 years ago, 220 white-tailed deers were introduced to Anticosti Island in Quebec, Canada, resulting in a modern population of over 160,000 individuals. An island environment can often lead to significant founder effect. Since new populations are derived from a small number of individuals, genetic drift and loss of genetic diversity is common within these island populations.

In this study, the researchers use genotyping-by sequencing (GBS) to generate 8,518 SNPs in order to compare patterns of genetic diversity and differentiation between the mainland and island populations. Clustering analysis shows that there is a relatively weak (<1%) but significant genetic differentiation between the mainland and island populations. The authors believe that this result could be due to the large number of founders (>200) and low rate of genetic drift since the founding of the insular population. The result also reveals that there is no significant differentiation between populations from 3 different regions on the island. Moreover, genetic diversity is actually found to be higher in the Anticosti Island populations than continental populations. This could be a result of a large founding population, providing a representative allelic diversity of the source population. These results support an absence of founder effect in white-tailed deer on Anticosti Island, suggesting that genetic diversity in introduced populations could be retained and potentially increase with a large number of founding individuals. 

Fuller, J., Ferchaud, A.L., Laporte, M., Le Luyer, J., Davis, T.B., Côté, S.D. and Bernatchez, L., 2020. Absence of founder effect and evidence for adaptive divergence in a recently introduced insular population of white‐tailed deer (Odocoileus virginianus). Molecular ecology, 29(1), pp.86-104.

http://www2.bio.ulaval.ca/louisbernatchez/pdf/(458)%20Fuller_Molecular_Ecology_2020.pdf

Molecular Ecology Journal Update

Monica Cheung– April 16, 2020

Week 6 : Evolutionary Relationships among humans and apes

Week 11: Primate Conservation Potluck - Conservation Genetics of the Philippine Tarsier: Cryptic Genetic Variation Restructures Conservation Priorities for an Island Archipelago Primate

In this article, 66 individuals from 17 localities of Tarsius syrichta across the southern Philippines were sampled using mitochondrial 12S ribosomal RNA (12S), Cytochrome B (CytB), and NADH Dehydrogenase Subunit 2 (ND2) gene fragments, nine nuclear microsatellites and genomic data extracted from tissues to empirically infer the geographic partitioning of the genetic variation within the Philippine tarsier. This was done with the aim of attempting to identify evolutionary distinct lineages that could then be applied for primate conservation. The results showed that their exists three principal evolutionary lineages, (1) Bohol-Samar-Leyte, (2) Dinagat-Caraga, and (3) Mindanao with eastern and western subclades of the Philippine tarsier that do not correspond to the current recognized subspecies. The authors argue until a comprehensive study of molecular, morphological and bioacoustics can occur, while existing evidence does not provide a basis for distinguishable taxonomic alternatives, it should at least provide enough evidence to partition the tarsier archipelago population into at least three genetic variants.

 

Warrenkevin Henderson

Primate Conservation Potluck

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138104/

Nature Journal Update 5/5: The draft genome of mandrill (Mandrillus sphinx): An Old World monkey

This article introduces the draft genome of the mandrill. Authors note that mandrill studies are limited, especially in comparison to other primate species. Something interesting they talked about was that genome sequencing has to meet two main criteria: (1) they have to be important in the evolutionary position within the phylogeny; (2) biomedical relevance to humans. 

For the genome sequencing, 284 Gb data providing 96-fold coverage was used to reconstruct the mandrill genome. Within the mandrill genome, there were 43.83% repeated elements and 21, 906 protein coding genes.  Comparative genomic analyses of MHC molecules of the immune systems of mandrills and humans showed there are 17 genes in the mandrill that have associated phenotypes in humans such as lung cancer and asthma. 627 gene families with 1, 293 genes were found to be unique to the mandrill (Figure 1a). 5,133 single orthologous genes were found to be shared between 12 species of primates (Figure 1a-b). Furthermore, phylogenetical analysis showed that the mandrill split from macaque, based upon mtDNA sequences occurred around 6.9-9.2 MYA, up from the previous estimate of 6.0-8.0 MYA (Figure 1c). 

Warrenkevin Henderson 

Nature Journal Post 16APR20 5/5

https://www.nature.com/articles/s41598-020-59110-3

Journal Update - BMC Evolutionary Biology: How unique is human chromosome 19?

Human chromosome 19, demonstrates a uniquely high level of gene density and diversity. To understand the uniqueness of these trait in humans, the authors compared the GC context and present of CpG islands on chromosome 19, with orthologous areas on 19 other primates species. They find that the striking similarities in all 19 primates species, suggesting that high gene diversity and density in these chromosome has been constant throughout primate evolution. They demonstrate a higher rate of nucleotide evolution in regulatory regions of these genes, which they suggest could be synonymous with other studies that find accelerated rates of evolution in genes coding for pregnancy and immune response.

Jack Richardson - Journal Update - BMC Evolutionary Biology.

Link to article: https://bmcevolbiol.biomedcentral.com/articles/10.1186/s12862-020-1595-9

Black Death Likely Altered European Genome -- Signatures from Two Distinct Populations

https://www.livescience.com/43063-black-death-roma-evolution.html

As we've learned in class, the persistence of certain alleles varies in humans based on the geographic / ecological context of their recent ancestry. In some populations, mutations may arise that are particularly protective or deleterious for their environment. Susceptibility to disease is one of, if not the biggest driver of human mortality. Occasionally, pandemics and epidemics can affect humanity on a global scale, ultimately resulting in a change in allele frequency due to selection for disease resistance or ability to recover.

The black plague was one such epidemic, wiping out ~30% of the world's population at the time. Certainly, there should exist genetic signatures of resistance to the epidemic -- some individuals were more or less prone to succumbing to the disease. But how to tease out those signatures?

An elegant study examined two distinct populations in the Netherlands, whose ancestors lived through the black plague in the exact same environment, but according to historical evidence, kept to themselves in terms of mate choice. One population was the Roma, who had migrated from northern India relatively shortly before the plague, and their Dutch natives. The researchers wanted to see if there were genes that were similar between the descendants of the native Dutch and Roma that also differed between the Roma descendants and the northern Indian population. The idea is that these genes may have conferred resistance to the plague and been selected for in both populations in the affected Netherlands, and that such genes would be much more concentrated in the Roma descendants than those of northern Indians from whom the Roma had split.

The researchers found one gene related to skin pigmentation, one gene that was pro-inflammatory, and a cluster of genes related to immune system function that met this criteria. The researchers believe that the immune system-related genes were selected for in both populations in the context of the plague, and that the pro-inflammatory gene may have been a boon to this effect, even if pro-inflammatory genes tend to be maladaptive under 'normal' circumstances.

Mack Hepker, Potluck 4/14/2019

Math shows how human behavior spreads infectious diseases

As we all continue to stay home because of covid-19, the pandemic demonstrates how our social behaviours could have major impact on the outbreak and transmission of infectious diseases. In this article, the authors criticizes the current prediction model for infectious disease. "We tend to treat disease systems in isolation from social systems, and we don't often think about how they connect to each other, or influence each other," said Chris Bauch, co-author of the paper. The new model developed by the team includes dynamic social interactions to the models already used for disease outbreaks and evolution. This model can help better anticipate how the viral strain emerge and react based on human responses to the outbreak.

Shown by the coronavirus, infectious diseases have the ability to evolve and move quicker than we can anticipate because of social behaviours. Adapting a new model to look at the spread of diseases could help public health workers better understand and respond to newly-emerged virus infections. 

Math shows how human behavior spreads infectious diseases
https://www.sciencedaily.com/releases/2018/08/180816081446.htm

Monica Cheung– April 14, 2020

COVID 19 produces a viral load 1000x higher than SARS

There's a lot of news and research about Covid-19, but I stumbled across this article which caught my eye.

Researchers examined the viral load in 9 patients in Germany:

"In SARS, it took 7 to 10 days after onset until peak RNA concentrations (of up to 5x10⁵ copies per swab) were reached," the researchers wrote. "In the present study, peak concentrations were reached before day 5, and were more than 1,000 times higher."

In a different study mentioned in this article, researchers found 97.5% of symptomatic patients develop symptoms within 11.5 days (which means the recommended quarantine period of 14 days is on target):

"The researchers estimated the median incubation period at 5.1 days (95% confidence interval [CI], 4.5 to 5.8 days). They found that 97.5% of patients who have symptoms do so within 11.5 days of infection (CI, 8.2 to 15.6 days)."

Also, in case anyone hasn't seen this yet, here is a map from Johns Hopkins University showing the distribution of Covid-19 in the US:

https://coronavirus.jhu.edu/map.html

I'm a nerd for geography, so I have been watching this map since the US got its first case. It is interesting to think that we have the technology to track the evolution of this virus in almost real time.



Article link: https://www.cidrap.umn.edu/news-perspective/2020/03/study-highlights-ease-spread-covid-19-viruses

Zac Truesdell, potluck 4/14

Evolutionary Medicine of Retroviruses in the Human Genome

Interest in virology has increased significantly due to recent circumstances. While this interest is specifically focused on COVID-19, readers should also revisit a recent review of evolutionary medicine of retroviruses in humans by Katsura and Asai (2019). Approximately, 5-8% of the human genome is comprised on endogenous retroviruses (HERVs) from viral sequences (resembling infectious retroviruses). Katsura and Asai emphasize the importance of understanding these retroviruses in preventing or reducing the effects of disease. For instance, abnormal expression of HERVs could be linked to multiple sclerosis. They also highlight that retroviral sequences can serve as transcription factors and specify sites for alternative splicing of transcripts. Katsura and Asai conclude that further studies of HERVs and modern infectious retroviruses must be conducted before we can develop finer-scale interpretations of their roles and use of them clinically.

Joshua Porter – 04/14/2020 Potluck

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093845/pdf/main.pdf

Coronavirus and Music

The structure of the coronavirus is basically a spheroid with protein 'spikes' jutting out regularly along the surface to help the virus latch onto host cells, where it injects its DNA and does nasty virus things. Now, "scientists" have developed a novel way of studying the novel coronavirus--with MUSIC! The protein structure of the binding spikes (above) has been translated into a musical score with each amino acid in the sequence corresponding to a different musical note. This isn't all pure whimsy, don't you worry dear reader; searching this new musical score for specific sequences of notes can help identify potential antibody binding sites to assist in the subsequent destruction of the virus. 

Why does this need to be done with music? Why take the time to set the score using the Japanese koto as the instrument of choice? Why stretch it out to make the entire thing almost two hours long? If it makes us happy, does it truly matter? Sometimes science can both do good and make us feel good at the same time. Stay healthy, my friends. 

Ryan McRae

Potluck 4/14

https://www.sciencemag.org/news/2020/04/scientists-have-turned-structure-coronavirus-music

Journal Update: Proceedings of the Royal Society B

Continent-wide effects of urbanization on bird and mammal genetic diversity

It is well known that urbanization affects life on Earth, but people do not often think about lack of  genetic diversity as a negative effect. Using raw genotype data from 41 mammal and 25 bird species as well as human population density and the Human Footprint Index, scientists found that mammals had lower effective population sizes, lower genetic diversity, and were more genetically differentiated than wild populations in urban environments. There was no consistent relationships detectable for birds. This shows us that urbanized areas not only disturb the mammal populations living within the area, but also render them more likely to suffer from effects of inbreeding.

https://royalsocietypublishing.org/doi/full/10.1098/rspb.2019.2497

Kristin Carline | Journal Update | 4/13/20

Week 12 : "Why we get sick" Potluck -The role of senescent cells in ageing

I chose this article because of the authors of “Why we get sick” talked about senescence. So, it sparked my interest. 

This article talks about cell signaling networks and mechanisms that underly the types of cellular senescence. Senescence is a process where cells cease dividing and undergo distinctive phenotypic alterations, such as chromatin and secretome changes, and tumor-suppressor activation.  Cellular senescence, while having been known to have irreversible cell-cycle arrest mechanisms acting to protect us from cancer, more recently have been shown to have a role has in assisting processes such as development, tissue repair, aging and age-related disorders. 

This figure shows a variety of cell extrinsic and intrinsic stressors that can activate the cellular senescence program.

This figure shows the hypothetical multi-step senescence model showing evidence that cellular senescence can be driven by epigenetic and genetic changes.  Progression to deep or late senescence may be driven by additional genetic and epigenetic changes, like chromatin budding, histone proteolysis and retrotransposition. These changes can be the driving force for further transcriptional change and senescence-associated secretory phenotype (SASP) heterogeneity (yellow, magenta, pink and blue dots). SASP is key in that it distinguishes cells from quiescent, terminally differentiated and other types of non-proliferating cells. 

Senescent cells are subdivided into two main classes based upon the kinetics of senescence induction and their functionality. Acute senescent cells are tightly orchestrated biological processes that can be representative of a wound healing, tissue repair, embryonic development. These processes halt expansion of certain cells and produce a SASP with defined paracrine functions. On the other other-hand chronic senescence is not programmed and does not target specific cell types, rather occurs due to age-related immunodeficiency or production of less proinflammatory SASPs. 



Warrenkevin Henderson
Potluck 13APR20 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214092/

Epigenetic Landscape during Coronavirus Infection

Epigenetic Landscape during Coronavirus Infection

Alexandra Schäfer and Ralph S. Baric

Coronaviruses (CoV) make up a large group of human and animal pathogens. Two of the most familiar coronaviruses include SARS-CoV (severe respiratory syndrome coronavirus) and MERS-CoV (Middle East respiratory syndrome coronavirus. Recently, studies show that viruses have complex processes that regulate the host epigenome and control innate antiviral defense processes, allowing for virus replication and pathogenesis. This paper looks at emerging coronvirus infections and the resulting new viral defense mechanisms.

Coronaviruses are enveloped RNA viruses and the viral particles are surrounded by ‘spike’-shaped glycoproteins, which give the viruses their characteristic microscopic ‘corona-like’ appearance. Both pathogens cause respiratory tract infections, with the most impacted individuals developing acute respiratory distress syndrome (ARDS).  Asymptomatic infections were rare during the SARS-CoV epidemic, MERS-CoV infections frequently result in asymptomatic infections leading to asymptomatic spread--similar to the asymptomatic spread of COVID-19 currently. 

As we discussed last week, Epigenetics is the study of any potentially stable and, ideally, heritable change in gene expression or cellular phenotype that occurs without changes in the underlying DNA. Viruses interfere with epigenetic regulatory programs within the host, such as histone modification, chromatin remodeling, and viral proteins that interact with the modified histones. Prior studies have noted viruses impacting the immune response by altering the epigenetic gene expression (turn on and off). The evolution of viral defenses and epigenetic effects that allow viruses to attack gene clusters, should be studied in the future.

I sent this paper out as a follow-up, but after reading the book, I thought it would be interesting to post about. This paper goes over two different coronaviruses, SARS-CoV (2002/2003) and MERS-CoV (2012), and touches on the selective pressure that increases the adaptability of the pathogen as a marker of success. Co-evolution is an important mechanism to ensure the viability within a host (and their immune response). Additionally, it is an in-depth article covering epigenetic mechanisms, gene activation and expression, and using epigenetics as a way to identify genes and develop antiviral drugs.

IMAGE: Epigenetic modification infection with highly virulent respiratory viruses--changes in the base state of host chromatin. Infection with H1N1-09 and SARS-CoV results in enrichment of H3K4me3 incorporation (green ovals) and depletion of H3K27 (red diamonds), and therefore in open, transcription-active chromatin. In contrast, H5N1-VN1203 and Middle East respiratory syndrome coronavirus (MERS-CoV) infection drives H3K27me3 enrichment and depletes H3K4me3 for a subset of genes, favoring a closed chromatin conformation that inhibits interferon-stimulated gene (ISG) expression


Kailie Batsche
Potluck for 14 April 2020
Link: https://www.ncbi.nlm.nih.gov/pubmed/28212305