Club EvMed this week

Pathogen selection for HLA gene diversity and its consequences for autoimmunity and cancer immunotherapy. Sign up here for the meeting link.

Tuesday, October 27th at 1pm EDT

headshot of Tobias Lenz

Join us for a conversation with Tobias L. Lenz of the Research Group for Evolutionary Immunogenomics at the Max Planck Institute for Evolutionary Biology in Ploen, Germany. Pathogen-mediated selection is a major driver of human evolution in general and of immune gene diversity specifically. A key component of the adaptive immune system are the human leukocyte antigen (HLA) genes, coding for molecules that present antigenic peptides to immune effector cells. The exceptional polymorphism at the HLA gene is assumed to reflect the need for diverse antigen presentation. However, an optimal immune response requires a delicate balance of maximizing recognition of pathogens while minimizing damage to self tissue by the immune machinery. As HLA molecules present both non-self and self antigens, depending on which antigens are presented by an individual’s HLA variants, this can trigger either pathogen resistance or autoimmunity. HLA-presentation of a broader antigen repertoire should thus be beneficial for pathogen recognition, but might also increase the risk for autoimmunity, leading to antagonistic selective pressures that shape the optimal antigen repertoire and thus HLA diversity in an individual.

Here Dr. Lenz will discuss this evolutionary trade-off for individual HLA diversity and present some examples from his work on the role of pathogens in the evolution of HLA diversity, but also on its consequences for autoimmunity and its role in immune checkpoint blockade therapy against cancer, a striking example for the success of evolutionary medicine. Attendees are encouraged to read Pierini and Lenz 2018, “Divergent allele advantage at human MHC genes: signatures of past and ongoing selection” and Chowell et al. 2019, “Evolutionary divergence of HLA class I genotype impacts efficacy of cancer immunotherapy.” Sign up here for the meeting link.

ClubEvMed: James DeGregori on Cancer

ClubEvMed: James DeGregori on Cancer

How recent characterizations of somatic mutations in humans inform an evolutionary understanding of aging and cancer

Monday, October 19th at 1pm EDT. Sign up here for the meeting link.

James DeGregori and his dog

Join us for a conversation with James DeGregori, Courtenay C. And Lucy Patten Davis Endowed Chair in Lung Cancer Research at the University of Colorado Anschutz Medical Campus. In the last five years, multiple studies have demonstrated that apparently healthy tissues in humans are patchworks of clones bearing somatic mutations, and the sizes and frequencies of these clones increases dramatically in old age. Often, there is clear evidence for positive selection for variants, which are frequently in genes frequently mutated in cancers, and yet the vast (VAST!) majority of these mutation-bearing clones will never develop into a cancer. We will discuss the implications of these findings for different evolutionary theories of aging and cancer. Attendees are encouraged to read Martincorena et al. 2018, “Somatic mutant clones colonize the human esophagus with age” and Kakiuchi et al. 2020, “Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis.” Sign up here for the meeting link.

Club EvMed on Covid this week

Assessing SARS-CoV-2 susceptibility in 400 species with comparative genomics Tuesday, October 6th at 12pm EDT with Elinor Karlsson. Sign up here for the meeting link.

Join us for a conversation with Elinor Karlsson, Associate Professor inBioinformatics and Integrative Biology at the University of Massachusetts Medical School and the director of the Vertebrate Genomics Group at the Broad Institute of MIT and Harvard. SARS-CoV-2, the virus that causes COVID-19, is a zoonotic pathogen that readily infects some non-human species, posing a risk to humans, if viral reservoirs are established in other species, and to other species, particularly those already endangered. Data on susceptibility and pathology in non-human species is sparse, with natural infection documented in fewer than a dozen species, but genomic datasets are far more substantial. We compiled genomic data for over 400 species and used the sequence of ACE2, the host receptor protein, to make a prediction of SARS-CoV-2 susceptibility. We also show that the viral binding domain of ACE2 is enriched for signals of natural selection in bats, the proposed source of the progenitor virus. By leveraging existing data resources, we completed this work in just four weeks in the midst of a global pandemic. While the risk predictions are preliminary, this work demonstrates how open genomic resources can be leveraged to address questions never envisioned in their original design.
Sign up here for the meeting link.

ClubEvMed October, 2020

ClubEvMed October, 2020

ClubEvMed has a terrific line up of speakers for October. Sign up for each session on the website

Club EvMed: Student Spotlight

Thursday, September 24th at 11am EDT

Join us for a special Club EvMed where we’ll be highlighting some of the exciting graduate student research in the field of evolutionary medicine. We will hear 12-minute research talks from Lafi AldakakChenlu Di, and Iman Hamid (see abstracts below). There will be a brief Q&A period at the end of each talk, plus breakout rooms after all 3 talks to allow for more in depth conversations with the speakers. Sign up here for the meeting link.

The evolution of immune sensitivity and tolerance under multiple costs of immunity and ecological feedbacks” by Lafi Aldakak, University of Zurich Institute for Evolutionary Medicine. We explore how immune resistance and tolerance are affected by the pathogen’s characteristics and the host’s life-history traits. We examine a situation where the molecular signatures of parasites, used by the host for identification, have a normal distribution overlapping with the host’s own. Due to epidemiological feedbacks, the more hosts tolerate the parasite, the bigger its prevalence and hence the risk of infection. We determine the evolutionary stable strategies of the host’s immune sensitivity and find that hosts tolerate parasites with high mimicry and low virulence. Long lifespan selects for tolerance in the innate immunity but high resistance in the adaptive immunity. This contradicts previous findings and results from our inclusion of epidemiological feedbacks and immune memory.

“The causes of strongly depleted recent adaptation in human disease genes” by Chenlu Di, University of Arizona. Despite the fact that our knowledge of gene-disease associations has greatly expanded, it is currently unknown if human non-infectious disease genes have adapted more or less than genes not involved in diseases. By a conservative comparison between human non-infectious disease and non-disease genes, we found a strong depletion of recent adaptation in human disease genes. This supports our hypothesis that disease genes are more likely to be genes that are sensitive to changing environments and have not adapted to new environments yet.

“Rapid adaptation to malaria in under 20 generations in the admixed human population of Cape Verde” by Iman Hamid, Duke University. Malaria has played a major role in human evolution as one of the strongest selective pressures in human history. Recent large-scale migrations have exposed human populations to new environments and diseases, such as malaria. How quickly humans can adapt to such a strong selective pressure and how this rapid adaptation shapes genomic variation remain unclear. Here, we develop ancestry-based methods to test for evidence of and characterize rapid adaptation to the malaria parasite, Plasmodium vivax, during the last 20 generations in the admixed population of Cape Verde.

Everything You Ever Wanted to Know About Race: And Why That’s Important for Evolutionary Medicine

Thursday, October 1st at 12pm EDT

headshot of Joseph Graves

Join us for a conversation with Joseph L. Graves Jr., Professor of Biological Sciences at the Joint School for Nanoscience and Nanoengineering, administered by North Carolina A&T State University and UNC Greensboro. Ongoing confusion concerning the nature and significance of human biological variation exists within the lay public, medical practitioners, and biomedical researchers. This occurs despite the fact that a core principle of evolutionary science is the importance of variation. This talk addresses how evolutionary principles can be better applied to understand health disparities associated with socially defined race. Attendees are encouraged to read Graves 2019, “African Americans in evolutionary science: where we have been, and what’s next” and Graves 2018, “Biological Theories of Race Beyond the Millennium” (in Suzuki and Von Vacano, Reconsidering Race: Social Science Perspectives on Racial Categories in the Age of Genomics), which will be shared upon registration. Sign up here for the meeting link.

Assessing SARS-CoV-2 susceptibility in 400 species with comparative genomics

Tuesday, October 6th at 12pm EDT

Elinor Karlsson headshot

Join us for a conversation with Elinor Karlsson, Associate Professor in Bioinformatics and Integrative Biology at the University of Massachusetts Medical School and the director of the Vertebrate Genomics Group at the Broad Institute of MIT and Harvard. SARS-CoV-2, the virus that causes COVID-19, is a zoonotic pathogen that readily infects some non-human species, posing a risk to humans, if viral reservoirs are established in other species, and to other species, particularly those already endangered. Data on susceptibility and pathology in non-human species is sparse, with natural infection documented in fewer than a dozen species, but genomic datasets are far more substantial. We compiled genomic data for over 400 species and used the sequence of ACE2, the host receptor protein, to make a prediction of SARS-CoV-2 susceptibility. We also show that the viral binding domain of ACE2 is enriched for signals of natural selection in bats, the proposed source of the progenitor virus. By leveraging existing data resources, we completed this work in just four weeks in the midst of a global pandemic. While the risk predictions are preliminary, this work demonstrates how open genomic resources can be leveraged to address questions never envisioned in their original design. Sign up here for the meeting link.

Survival of the Friendliest

Tuesday, October 13th at 12pm EDT

cover of the book Survival of the Friendliest by Brian Hare and Vanessa Woods

Join us for a conversation with Brian Hare, Professor of Evolutionary Anthropology at Duke University. The only way to understand what it is to be human is to know what it is like to be not human. In this talk we will explore the minds of our closest relatives, bonobos and chimpanzees, and dogs — our closest friend. We will look at how these animals help us understand what makes us human, and how our minds came to be. We will arrive at the idea that it was friendliness that powerfully shaped both the bodies and minds of bonobos and dogs during their evolution. We will then consider if our own species evolved due to selection for friendliness. We will argue that comparing our friendly nature to other animals solves the paradox of human kindness and cruelty and points to the need for cross-group friendships to encourage a friendlier future. These ideas are explored in Hare’s new book, Survival of the Friendliest: Understanding Our Origins and Rediscovering Our Common Humanity. Sign up here for the meeting link.

How recent characterizations of somatic mutations in humans inform an evolutionary understanding of aging and cancer

Monday, October 19th at 1pm EDT

James DeGregori and his dog

Join us for a conversation with James DeGregori, Courtenay C. And Lucy Patten Davis Endowed Chair in Lung Cancer Research at the University of Colorado Anschutz Medical Campus. In the last five years, multiple studies have demonstrated that apparently healthy tissues in humans are patchworks of clones bearing somatic mutations, and the sizes and frequencies of these clones increases dramatically in old age. Often, there is clear evidence for positive selection for variants, which are frequently in genes frequently mutated in cancers, and yet the vast (VAST!) majority of these mutation-bearing clones will never develop into a cancer. We will discuss the implications of these findings for different evolutionary theories of aging and cancer. Sign up here for the meeting link.

Pathogen selection for HLA gene diversity and its consequences for autoimmunity and cancer immunotherapy

Tuesday, October 27th at 1pm EDT

headshot of Tobias Lenz

Join us for a conversation with Tobias L. Lenz of the Research Group for Evolutionary Immunogenomics at the Max Planck Institute for Evolutionary Biology in Ploen, Germany. Pathogen-mediated selection is a major driver of human evolution in general and of immune gene diversity specifically. A key component of the adaptive immune system are the human leukocyte antigen (HLA) genes, coding for molecules that present antigenic peptides to immune effector cells. The exceptional polymorphism at the HLA goes is assumed to reflect the need for diverse antigen presentation. However, an optimal immune response requires a delicate balance of maximizing recognition of pathogens while minimizing damage to self tissue by the immune machinery. As HLA molecules present both non-self and self antigens, depending on which antigens are presented by an individual’s HLA variants, this can trigger either pathogen resistance or autoimmunity. HLA-presentation of a broader antigen repertoire should thus be beneficial for pathogen recognition, but might also increase the risk for autoimmunity, leading to antagonistic selective pressures that shape the optimal antigen repertoire and thus HLA diversity in an individual.

Here Dr. Lenz will discuss this evolutionary trade-off for individual HLA diversity and present some examples from his work on the role of pathogens in the evolution of HLA diversity, but also on its consequences for autoimmunity and its role in immune checkpoint blockade therapy against cancer, a striking example for the success of evolutionary medicine. Attendees are encouraged to read Pierini and Lenz 2018, “Divergent allele advantage at human MHC genes: signatures of past and ongoing selection” and Chowell et al. 2019, “Evolutionary divergence of HLA class I genotype impacts efficacy of cancer immunotherapy.” Sign up here for the meeting link.

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