SCI2022 Genetics and Evolution Course Manual - University College Maastricht 2024-2025 PDF

SCI2022 Course manual 2024-2025 University College Maastricht Course Manual Genetics & Evolution (SCI2022) 2024-2025 1 back to contents table ...

SCI2022 Course manual 2024-2025 University College Maastricht Course Manual Genetics & Evolution (SCI2022) 2024-2025 1 back to contents table  SCI2022 Course manual 2024-2025 Contents CONTENTS............................................................................................................................................................. 2 GENERAL INFORMATION....................................................................................................................3 INTRODUCTION...................................................................................................................................................... 3 COURSE OBJECTIVES................................................................................................................................................ 5 STUDY MATERIALS.................................................................................................................................................. 6 LECTURES.............................................................................................................................................................. 6 ASSESSMENT......................................................................................................................................................... 7 Presentation assignment............................................................................................................................... 7 Written exam............................................................................................................................................... 10 ATTENDANCE EXPECTANCY..................................................................................................................................... 10 COURSE COORDINATION........................................................................................................................................ 10 PBL TASKS........................................................................................................................................ 11 PBL-TASK 1: MENDELIAN RULES AND EXCEPTIONS..................................................................................................... 12 PBL-TASK 2: ORIGINS AND EDITIONS OF THE BOOK OF LIFE.......................................................................................... 14 PBL-TASK 3: POPULATION GENETICS: ADAPTATION, EVOLUTION AND HIGHLY PREVALENT DISEASES.................................... 17 PBL-TASK 4: EARLY GENOMIC CONFLICTS & SOLUTIONS: ENDOSYMBIOSIS AND MULTICELLULARITY..................................... 19 PBL-TASK 5: SPECIATION AND PHYLOGENETIC TREES.................................................................................................. 21 PBL-TASK 6: COEVOLUTION................................................................................................................................... 22 PBL-TASK 7: SEX AND SEXUAL SELECTION................................................................................................................. 24 PBL-TASK 8: INCLUSIVE FITNESS THEORY AND COOPERATION....................................................................................... 25 PBL-TASK 9: PLACENTAL BATTLES: PARENT-PARENT AND PARENT-OFFSPRING CONFLICTS.................................................. 27 PBL-TASK 10: WHAT MAKES HUMANS (TYPICALLY) HUMAN?....................................................................................... 29 APPENDIX I: ADDITIONAL LITERATURE LIST PER PBL TASK................................................................. 31 APPENDIX II: PRESENTATION ASSIGNMENT...................................................................................... 33 ASSIGNMENT TOPICS - EXAMPLES............................................................................................................................ 34 I - Genetics & Evolution................................................................................................................................ 34 II - Evolutionary Biology, Medicine and Psychology..................................................................................... 35 APPENDIX III: STUDY SKILLS AND PROBLEM-DIRECTED LEARNING..................................................... 38 First meeting of the course.......................................................................................................................... 38 Working with the seven steps during PBL sessions...................................................................................... 38 Leading a group discussion.......................................................................................................................... 39 Participation in the study group.................................................................................................................. 39 Evaluation.................................................................................................................................................... 39 Science code & Plagiarism, AI-text tools...................................................................................................... 40 2 back to contents table  SCI2022 Course manual 2024-2025 General Information 3 back to contents table  SCI2022 Course manual 2024-2025 Introduction Ever since Darwin wrote his book “On the Origin of Species”, the theory of evolution has been the main unifying theorem in life sciences. Molecular biologists study the structure and function of genes and proteins, anatomists study the structure of organs, a physiologist studies the mechanisms in our body, and an ethologist studies behavioral patterns displayed by animals (including man). Evolution connects all these fields, as the evolutionary context explains why these genes, proteins, anatomical structures, physiological mechanisms and behavioral patterns evolved to become what we are able to observe. A structure or mechanism may be studied from different perspectives: and anatomist or physiologist will ask: how does it function), an evolutionist asks: why did the structure evolve? How did it originate? What purpose does it serve? The fact that evolutionary analysis is always possible, distinguishes life sciences from physical (and chemical) sciences. Why is evolution so important in life sciences? Does evolution define the distinction between life sciences and physical sciences? These questions are at the core of what evolution is about. Evolution is the ongoing modification of living organisms as the result of natural selection. Only living beings are subject to evolution: natural selection is a force that operates only in organisms that reproduce. As organisms multiply, their numbers increase. If there were no selection forces, their numbers would increase indefinitely. However, organisms will die - some will die earlier than others. If there is genetic variation that affects their likelihood of survival or reproduction, then organisms with characteristics most favorable for survival or reproduction will be selected. Although the outcome of evolution is not random, the process itself is random: evolution is not driven by purpose, decision or some form of intelligence. This is, in a nutshell, what evolution entails. Natural selection cannot operate on entities that do not multiply. Take the example of a rock: a rock is not the product of natural selection: a rock does not multiply as a living being does, and a rock does not have heredity: it cannot pass on a favorable characteristic to its offspring. Hence, in the case of a rock, there is no material for natural selection to act upon. Thus, evolution can only occur if there is heritable, genetic variation in a population. Hence, DNA is the canvas of evolution. For understanding the details of the evolutionary process, knowledge of genetics is indispensable. This is the reason why both genetic and evolutionary theory are discussed in one course. The course provides a basic grounding in molecular and population genetics, that is needed to understand the mechanisms of evolutionary change. First, we will discuss transmission genetics. How are traits transmitted from one generation to the next? Understanding the laws of Mendel and how these laws explain qualitative and quantitative traits is of importance. Genes (genotypes) determine characteristics (phenotypes, traits), yet how does this work? Molecular genetics has revealed that genes consist of DNA and that there is heritable information encoded in the nucleotide sequence of this macromolecule. This information is replicated during cell division and passed on to next generations of cells and individuals. The nucleotide language of DNA is transcribed into RNA and may be translated into an amino acid language to synthesize proteins. Mutations in DNA may affect gene, RNA and/or protein function. A relevant extension of the connection between genotypes and phenotypes is the regulation of gene expression. This is studied within the field of molecular epigenetics. We will focus on genomic imprinting, i.e. the phenomenon that the effect of a gene depends on whether the mother’s or a father’s allele is expressed. Imprinting is an example of an evolutionary epigenetic construct, i.e. it has become a fixed, class-specific (Mammalia) developmental biological mechanism. We 4 back to contents table  SCI2022 Course manual 2024-2025 will also examine how the expression of a phenotype is not only dependent on the underlying genotype, but also on the interaction between genotypes and the environment. We will see how this provides important plasticity/adaptability to organisms in their environment, the importance of gene-environment interaction in health and disease and how epigenetics may contribute to evolution. Since only living organisms multiply, the theory of evolution and natural selection is only applicable to life sciences. This difference between life sciences and physical sciences is so fundamental that it is translated into a formal distinction between two kinds of scientific explanations. Proximate causal explanations concern the physical and (bio)chemical causation of phenomena in life sciences (microlevel - how does it work?). Such explanations provide insight into cellular and molecular mechanisms that explain changes within or differences between organisms. The aim of proximate causal explanations is thus to identify causes of processes or mechanisms for change within the lifetime of a single organism. For instance, molecular geneticists investigate how individual characteristics evolve during development. Ultimate causal explanations aim to explain why specific traits have been selected during the course of evolution (macrolevel – what is the purpose of an evolved trait? in the bigger scheme of things). Why do many animals senesce, but many plants and fungi hardly at all? Why is the number of males and females in most species almost equal? These explanations tell us why specific genotypes have been preserved through selection on phenotypes. Evolutionary analyses also aim to address causation, i.e. how and why natural selection shaped traits (shape, function, mechanisms) under study, yet at a many-generations time scale and at the population and species level rather than between two generations or at the level of individuals. Course objectives After this course, students are able to: - analyze phenomena within biology, medicine, and psychology from an evolutionary perspective - make calculations and predictions based on the Hardy-Weinberg theorem by using the laws of Mendelian genetics - distinguish different types of mutations and their functional implications after transcription and translation - list and describe the processes that maintain genetic diversity in populations - use examples to appreciate the role of epigenetics and genomic imprinting in evolutionary processes - describe the major evolutionary transitions in the history of life - use principles of game theory to explain kin selection and parental investment - compare and evaluate phylogenetic trees based on provided speciation events - differentiate between reproductive barriers at different stages of reproduction - explain and apply the concepts of reciprocal selection and coevolution - describe the evolutionary advantages of sexual selection - analyze and apply different hypothesis about the evolution of the human brain 5 back to contents table  SCI2022 Course manual 2024-2025 Study Materials Throughout the course, the book by Zimmer, C. & Emlen, D.J.: Evolution, making sense of Life, 3rd edition (2020), Robertson & Company, Greenwood Village, CO, USA, will be used. As this book is not yet available via the UM library, it is recommended students procure this book for themselves. The book by Zimmer & Emlen is used in Evolution Biology courses at several Universities throughout the world; hence, there is a fair chance that second-hand copies are available for sale on line (1st (2013) or 2nd (2016) edition). The literature references in this course are derived from the 2020 edition. The course currently comprises 10 problem-based learning (PBL) tasks. A list of required literature is provided at the end of each task. Furthermore, an appendix with additional reading connected to the individual PBL-tasks is provided for further context (see: Appendix I). Most of these references are available via the UM server using the DOI (Digital Object Identifier), included in the literature list. For literature that is not available via the UM journal or book subscriptions, we have added the PDFs on Canvas (under Modules – Literature). Given the sheer amount of information available on evolution, it makes perfect sense to divide the reading among PBL-group members, such that the whole PBL-group benefits from contributions by individuals, and all save time in the process. It is permitted, encouraged even, to look for other sources for additional information (e.g. Wikipedia, online lectures, explanatory video clips); some suggestions have been provided already in relation to individual PBL-tasks in Appendix I. N.b.: always aim for scientifically verified information. Lectures A series of 6 lectures by various UM-based experts, accompanies the course. The lectures touch upon various topics associated with aspects of (human) evolution. These lectures are scheduled such that they connect to the PBL-tasks regarding content and timing. As such, these course lectures support the PBL- tasks, and provide opportunity for interaction with the expert teachers. The lectures are complementary to the PBL tasks and course book – it is highly recommended to attend these lectures as some material is not covered in the handbook. As the content of the lectures adds to the pre- and post-discussions in the tutorial group meetings, its contents are part of the examination. The lecture slides will be published before or soon after the lecture, depending on the lecturer’s preferences. Week Lecture topic Lecturer 1 Intro to evolutionary biology B. Schmitz 2 Molecular genetics & epigenetics J.W. Voncken 3 Evolutionary biology L. van Griethuijsen 4 Evolutionary medicine; cancer B. Schmitz, J.W. Voncken 5 Epigenetics in evolution J.W. Voncken 6 Evolution of social behavior and the brain M. Moerel 6 back to contents table  SCI2022 Course manual 2024-2025 Assessment This course contains two elements of assessment: 1. a group presentation assignment (40% of the overall course grade) – for more information, see below; 2. a written exam (60% of the overall course grade). Presentation assignment Part of the course on Genetics and Evolution is a presentation assignment. The aim of this training is that a) students deepen their knowledge/insight on genetics, epigenetics and/or about evolutionary explanations and their application to phenomena in the living world (e.g. behavior, psychology, medicine) and b) are able to explain this to peers. The assignment is a group task; assignment teams are composed of a maximum of 3 students, who all belong to the same PBL-group. The assignment comprises a presentation, which is to be presented at the end of the course. Topics either relate directly to (an aspect of) Genetics and/or Evolutionary Biology, Medicine, Psychology. A list of potential topics (and starting literature) is provided (see: Appendix II). Please note that students are free to choose any other topic, as long as the Genetics and Evolutionary aspect is represented in the topic. Last years’ topics are not allowed, unless the students can prove a substantially different, novel perspective. Deadline Action Week 3 – Monday (Sep 16, midnight) Topic choice & Outline Week 5 – Wednesday (Oct 2, midnight) Deadline draft version - send to reviewers Week 6 – Monday (Oct 7, midnight) Peer review reports – discuss in class on Tue Week 6 - Friday (Oct 11, tutorial timeslot) Final presentation Format of the final presentation Every group has 15 minutes for the presentation, followed by 5 minutes for questions and group discussion. The presentation should contain at least the following elements: - General introduction topic, - Explanation of context & relevance - Current knowledge gap - Focus: research question/hypothesis - Discussion: advanced understanding / recently published literature - Synthesis: remaining challenges & perspectives (provided in literature or by the students) - Conclusion(s) - Group discussion (presenters lead the discussion) 7 back to contents table  SCI2022 Course manual 2024-2025 Assessment of the final presentration The assessment of the presentation will be based on:  The quality of the introduction: ability to explain context and relevance of the topic, your research question in a comprehensive manner, such that the audience gains sufficient insight to understand the context and the rationale behind your topic choice.  The quality of the academic synthesis: ability to frame the problem/topic and explain how novel insight contribute to a better understanding.  The Q&A and academic discussion: ability to provide evolutionary/(epi)genetic perspectives to the problem and answer questions.  The quality of the presentation: quality of slides, communicative skills, professional attitude. A grading rubric will be provided in the Canvas course. The presentation should be theoretically informed. You do not have to explain basic concepts discussed in the course, since you are presenting to students from your own discipline. However, don’t take all background knowledge for granted either! The tutor will assess the presentations, supported by a second assessor. The presentation is the result of a cooperation of multiple students. There are no requirements as to who gives the presentation. You may present together, or decide to have one student present and have the other students lead the discussion and answer the questions. Either way, keep in mind that you will receive a group grade for this assignment. Your tutor will assess the final product; we cannot evaluate whether you divided the work equally. It is your own responsibility to assure each team member invests approximately the same amount of work. When information is derived from a scientific article, university textbook or internet source, make sure citations and references are correct and complete. Not doing so is considered a form of plagiarism. Unauthorized use of AI also classifies as fraud and will be sanctioned under the Rules and Regulations (also see: Appendix III for additional information). Format of the presentation draft The presentation draft contains two elements: - the preliminary slides of the presentation - a draft report on the content of the presentation It is impossible to provide constructive feedback on a list of bullet points. Although it is hard to set a strict guideline for a draft, keep in mind that a draft is more than an outline: it should be a comprehensive overview comprising content on most if not all (presentation) elements mentioned above. Use a minimum of 1500 words as a guideline. Keep in mind that the more elaborate the presentation draft is, the more feedback can be expected and the less work needs to be done in order to finish the final presentation. In essence, a draft is a nearly complete and finished presentation outline, with the exception that it can still be changed. Feel free to specify and address any questions that you as presenters may still have with regard to the content of the presentation (facts, theories, sources, interpretations). Lastly, please make sure to clearly link specific sections of the report to specific slides. 8 back to contents table  SCI2022 Course manual 2024-2025 Format of the peer-review Part of the assignment is a peer-review. Reviewing another each other’s work provides valuable feedback for the presenters, and insight into what constitutes a good presentation. Each team writes peer-reviews for 2 presentation drafts by other teams (within the same tutorial-group – schedules for peer-reviews will be published on Canvas). Peer-reviews will be assessed on quality; the effort (i.e. quality) that was invested in the peer-review will be awarded with extra points towards the final grade for the presentation assignment: 0.5 pts extra for an insightful peer review report, 0 pts for a superficial, insufficiently critical review, or 0.5 pts deducted for a lack of serious effort. N.b: a ‘good’ peer-review does not guarantee a ‘good’ final grade on a presentation. A peer-review should be constructive; simply indicating that something is well-formulated and easy to understand may sound nice, but does not provide much direction to the presenters with regards to improvements. The presentation drafts and peer-reviews will be discussed during the final PBL-session (i.e. tutorial group). While composing and processing peer-feedback, also reflect on your own work. Guidelines on what each peer-review should include are: A brief summary on the content and (projected) message of the presentation (approximately 100- 150 words): this allows both the reviewer and the author to check whether the content is understood. Adding comments to a draft in the margins is welcomed. Major comments and criticisms on (any of) the elements of presentation draft (minimum 500 words): starts with the most prominent issues and ends with minor ones. Explain in clear, complete and comprehensive sentences why certain areas represent e a positive aspect of the draft presentation or a matter of concern, and provide suggestions on how to improve. This part of the peer-review focuses mainly on the content part of the presentation assignment. Minor comments and criticisms of the presentation (approximately 100 words): once the major concerns have been laid out, minor comments and criticism can be included (e.g. mislabelling of figures or tables, spelling or grammar mistakes, etc.). This part of the peer review focuses on the delivery part of the presentation assignment. Double Check:  upload all peer reviews on Canvas (please adhere to instructions); in addition,  remember to send copies of the review to the teams whose draft version were peer-reviewed. 9 back to contents table  SCI2022 Course manual 2024-2025 Written exam The 10 topics discussed in this course will be covered in the written exam during exam week. Please note that the content of the lectures adds to the pre- and post-discussions in the tutorial group meetings. Therefore, the content of the lectures is part of the examination. Re-sit In order to receive a grade for the exam a student is expected to make a serious attempt at passing the exam. If it is not deemed a serious attempt, a student will not receive a grade and the chance for a re-sit is forfeited. The same applies to the assignment. Students who initially fail the course, but who took part in all of the assessments during the course, are eligible for a re-sit. N.b.: The re-sit grade replaces the overall course grade – the partial assignment-grade is no longer valid. Inspection and Feedback Feedback on the group assignment will be provided in Student Portal. Students can obtain individual exam feedback by submitting a request for inspection (e-mail the coordinators). Attendance expectancy This course has a 100% attendance expectancy (and an 85% attendance requirement). All proceedings during the PBL sessions are important and relevant for a students’ learning process. In case a student is unable to attend a meeting, a student is expected to inform the tutor at least one hour prior to the meeting; please provide a short explanation for the unforeseen absence. Attendance during the official assessment moment (final exam) is, of course, mandatory. Note that any student carries his/her own responsibility for catching-up on information that may have been missed during an absence. We expect students to contact (one of) the PBL-group members to be informed about learning goals and/or any other relevant information. A lack in knowledge because of a missed session will not be accepted as an excuse. Course coordination J. Willem Voncken, PhD, eng Dept. Genetics and Cell Biology, Faculty of Health, Life sciences and Medicine, UM [email protected] Bram Schmitz, MSc University College Maastricht, Faculty of Science and Engineering, UM [email protected] 10 back to contents table  SCI2022 Course manual 2024-2025 PBL Tasks 11 back to contents table  SCI2022 Course manual 2024-2025 PBL-Task 1: Mendelian rules and exceptions Ever since the ancient Persian and Greek scholars, scientists have been interested in how traits are carried over between generations. Gregor Mendel, a fairly recent exponent of mankind’s desire to understand inheritance, defined the most basic principles of heritability, which became famous as Mendel’s Laws of Inheritance (1866). However, as the study of genetics took flight over the last two centuries, it was soon discovered that inheritance does not always follow Mendelian principles. In fact, some now argue that simple ‘Mendelism’ is more often the exception than the rule: many interesting traits appear not distributed in a ‘binary fashion’ in populations (like, e.g., the color or shape of a pea), but represent quantitative, normal-distributed features. An example of this is the trait height in the population (see picture below: women dressed in white, men in black; numbers in feet/inches). Many psychological traits also follow a normal distribution. Do Mendel’s laws apply to these traits, or is a new set of laws required? The observation that height per se is heritable, is not surprising: if both your parents are tall, you are likely to become tall as well. However, heritability estimates of height vary in populations: a study in Australia showed that height heritability was 80%, while a study in Western Africa reported only 65%. How do researchers get to these estimates? How can it be that the same trait varies across studies and between locations? And most importantly: what does an estimate of heritability mean? The basic rules of Mendelian inheritance should also apply to sex chromosomes; women have two X chromosomes (XX) in each cell, men have an X and a Y chromosome (XY). The phenotypic expression of recessive diseases linked to sex chromosome-linked alleles, however, proceeds differently from autosomal diseases. The laws of Mendel predict that X-linked recessive diseases will be more prevalent among men. Examples thereof are hemophilia and color blindness. The frequency of such diseases is easy to calculate since the expression in males is mono-allelic. Given the patterns of inheritance, it is not hard to see why diseases located on the X-chromosome should be more prevalent in men than in women. Unexpectedly, the syndrome of Rett (disease frequency is ±1:15.000), an X-linked recessive genetic disease, is far more prevalent in women (about 99% of the cases) than in men. Early symptoms of this intellectual disability syndrome include disturbed (goal-directed) hand movements and altered development of speech; at later stages, autistic-like behavior is often observed. Is Rett syndrome an exception to the rule that X-linked disease has a higher prevalence in men? 12 back to contents table  SCI2022 Course manual 2024-2025 Exercises/homework: heritability estimations of traits; probability calculations (1) John and Martha are contemplating having children, but John’s brother has galactosemia (a rare autosomal recessive disease), and Martha’s great-grandmother also had galactosemia. Martha has a sister who has three children, none of whom has galactosemia. What is the probability that John and Martha’s first child will have galactosemia? (2) A woman and her spouse are both heterozygous for an autosomal recessive gene (a) for albinism. If they have dizygotic twins, what is the probability that both of the twins will have the same phenotype for pigmentation? Explain your answer. (3) In a hospital in Hyderabad, two young women, Nisha and Ann, have delivered a baby on the same day. However, an unfortunate error was made in the identification of the babies, and now it is not clear anymore which baby belongs to which mother. Both Nisha and Ann have blood type A, Nisha’s spouse Nikhil has blood type AB, while Abinandan, Ann’s husband, has blood type O. Baby 1 has blood type A, baby 2 has blood type O. One of the local doctors believes that on the basis of these data the problem is solved. Another doctor suggests to also determine the Bombay genotype of the people involved. Baby 2 appears to have the hh genotype, while baby 1 is Hh. Nisha and Nikhil are both Hh; Ann is also Hh, while Abinandan carries the HH genotype. Can you determine which baby belongs to which set of parents? People of blood type A have a molecule called antigen A on the surfaces of their red blood cells (RBC). Blood type B corresponds to RBCs with antigen B. A person with genotype AB has RBC with both the A and B antigens, and the red cells of a person with type O blood carry neither antigen. The I gene encodes enzymes that place the A and B antigens on the RBC cell surface. The three alleles are IA, IB, and i. People with blood type A may be either I AIA or IAi; type B corresponds to IBIB or IBi; type AB to IAIB; and type O to ii. Even though the IA and IB alleles are co-dominant, the alleles segregate separately between generations. Just like two different alleles at the same locus may interact in a heterozygote to produce a particular phenotype (like the AB blood type), also genes at two different loci may interact. The Bombay phenotype, for example, is a result of two interacting genes: the I and H genes. The relationship of these two genes affects the expression of the ABO blood type. The product of the H allele is an enzyme that inserts a sugar molecule onto a particular protein on the red blood cell surface. The recessive allele h produces an inactive form of this enzyme, that cannot insert the sugar molecule. The A and B antigens attach to the sugar molecule that the H gene controls. As long as at least one H allele is present, the ABO genotype dictates the ABO blood phenotype. However, in a person with genotype hh, the A and B antigens cannot adhere to the red blood cell, and they fall away. This person expresses blood phenotype O, but may have any A/B/O-related blood genotype. Required literature PBL-task 1:  Zimmer, C. & Emlen, D.J. (2020) Evolution, making sense of Life, 3 rd edition, Robertson & Company, Greenwood Village, CO, USA (Chapter 5.1-5, 5.6-7; Chapter 6.6-9; Chapter 7.1-4)  Campbell, N.A. et al. (2018) Biology. San Francisco, Pearson, 11th edition (Chapters 14.1-3; Chapter 15) https://library.maastrichtuniversity.nl/resources/libsearch/ 13 back to contents table  SCI2022 Course manual 2024-2025 PBL-Task 2: Origins and editions of the book of life The human genome has often been compared to a library full of information, or the “book of life”: an instruction book, containing, in a large continuous single recipe, the description of ‘how to design an organism’; the design is written in nucleic acid language. For any person, her or his genes (read: an individual’s genotype) provide the cells with a set of instructions for its function (read: phenotype). Also, from the moment we are conceived, every cell type knows exactly how to use this “book of life”. The human instruction book adheres to particular characteristics:  the human book of life consists of 23 chapters;  chapters comprise a series of unique sentences, some of which form paragraphs;  although there is no rule to the length of the sentences, sentences consist of three-lettered words;  words are written as combinations of only 4 different letters;  words in any sentence appear to be interrupted by stretches of non-informative gibberish. More directions …  to use the information in the book, every sentence is first rewritten in a different dialect (4 letters);  the sentences in the dialect are often edited to remove the gibberish, and translated into a different language (20 letters);  the translated words are decorated with chemical cues (100’s of them). What’s even more astonishing:  the book of life has learned how to read and photocopy itself: moreover, it contains the information to make the tools required to accomplish these tasks;  photocopies are almost never perfect: the photocopying process causes damage to the nucleic acid language, and sometimes new editions contain different letters/words that change ‘the sentences, the paragraphs and/or the recipe’; this can be advantageous or non-advantageous for a human. Can you explain the metaphors above? Start by filling-in the corresponding scientific terms for each of the words written in italics. 14 back to contents table  SCI2022 Course manual 2024-2025 From the last half of the 19th century until the first half of the 20th century, major strides forward were made in our understanding of the origins of life around us. The long-held doctrine that life could arise from combination of 4 abiotic elements (Greek philosophers: cosmogenic theory; generatio spontanea) was formally abandoned round 1880 (Louis Pasteur), preformationists were proven wrong by epigenesists (i.a. Waddington), it was established that each and every cell in an organism’s body was derived from another cell ((Virchow; omnis cellula e cellula), and finally the fundamentals of the genetic code and genetic heritability were laid down, (J Watson & F Crick; Central Dogma). In 2000, the sequence of a nearly complete human genome was published for the first time: it was believed by many, now that the genetic blue print (genotypes) could be read, the outcome (phenotypes) could be predicted for every human being. Or could it? Although dogmas can be useful to understand the basis of a phenomenon, such initial views often led to tunnel-vision. The central dogma led to a fundamentally erroneous projection of how genotypes translate into phenotypes (“genetic astrology”). Owing to fundamental research over the past 3 decades, we now know that genes interact with the environment, that this interaction is mediated and controlled by epigenetic processes that enable accessing genetic information when & where needed and, that therefore using a gene is more essential than having a gene: “only under the right conditions, the sentences are read”. Hence, epigenetic regulation permits a degree of phenotypic flexibility and adaptability. For example, studies in rodents and humans show that exposure to stressors early in life, results in long- lasting physiological and behavioral changes. Children born underweight to mothers that suffered from famine during the infamous Dutch ‘Hunger winter’ (WWII), were more likely to develop obesity and cardio- vascular disease later in life. Barkers’ hypothesis aims to explain this by means of phenotypic adaptability. In rodents, bad motherhood produces stressed pups; although this ‘stress phenotype’ appears heritable, luckily – it is also reversible and thus adaptable. Another example: if all cells would use all of their DNA in the same manner, multicellular organisms would merely constitute a collection of similarly looking and functioning cells. Yet, the human body is composed of more than 200 different cell types, each with specific morphological and functional features. From early onward in development, establishing the human body plan requires cells to commit to a certain lineage and assume their specific functions at the right time and place. And yet, all cells carry the same genetic information. How do cells do this? Clearly, there must also be some form of fixed developmental programming? Can you explain the above, seemingly contradictory (underlined) statements? Considering the “book of life” to be a ‘recipe book’ – apparently the chief-cook (YOU!) is able to manipulate the outcome of a recipe in ways that do not alter the written recipe… the Nature vs Nurture discussion seems relevant in this context. How does epigenetics relate to Lamarckian inheritance? In what ways could epigenetics have contributed to evolution? 15 back to contents table  SCI2022 Course manual 2024-2025 Exercise/homework: making sense of DNA mutations Can you translate these 5 coding DNA sequences to their respective one-letter peptide codes? What type of mutation(s) occurred in relation to the reference sequence (=top: 0)? What are the consequences for the translated product (protein)? 0) ATG.ATT.TGT.GCT.AAT.CGT.GAA.GCT.GAT.ACT.CAT.ATT.TCT.TAA 1) ATG.ATC.TGC.GCG.AAC.CGC.GAG.GCC.GAC.ACG.CAC.ATC.TCG.TGA 2) ATG.ATT.TGT.GCT.ACT.CGT.GAA.GCT.GAT.ACT.CAT.ATT.TCT.TAA 3) ATG.ATT.TGT.GCT.AAT.CTT.GAA.GCT.GAT.ACT.CAT.ATT.TCT.TAA 4) ATG.ATT.TGT.GCT.AAT.ACG.TGA.AGC.TGA.TAC.TCA.TAT.TTC.TTA A: The codon AUG both codes for a methionine and serves as an initiation site: when the AUG codon is part of the Kozak consensus sequence, the AUG acts as the "start" codon that signals the initiation of protein translation to ribosomes. As a consequence, methionine is initially often incorporated at the first, N-terminal position of proteins in eukaryotes and archaea during translation; next, the N-terminal Met is typically removed from the mature protein by post-translational modification. AUG is the most common start codon; the other start codons listed are rare in eukaryotes. B: The stop codons (UAG, UAA, UGA) terminate translation and are designated: amber, ochre and opal, respectively. Required literature PBL-task 2:  Zimmer, C. & Emlen, D.J (2020) Evolution, making sense of Life, 3 rd edition, Robertson & Company, Greenwood Village, CO, USA (Chapter 5.1-5, 5.6-7; Chapter 7.1-5).  Campbell, N.A. et al. (2018) Biology, a global approach, 11th edition, Pearson, 330 Hudson Street, New York, NY 10013, SUA (Chapters 7.1-8 & 28.1; Chapters 12.2-3; 16.2; 17.2, & 17.5; 18.2-5) https://library.maastrichtuniversity.nl/resources/libsearch/  Goldberg et al. (2007) Epigenetics: a landscape takes shape. Cell 128(4):635-8. https://doi.org/10.1016/j.cell.2007.02.006  Powledge, T. M. (2009). Epigenetics and Development: Understanding how epigenetics works at the molecular level can be mind-boggling. BioScience, 59(9), 736-741. https://doi.org/10.1525/bio.2009.59.9.3  Self-study documents on Epigenetics; JW Voncken (Canvas  Modules  Literature). 16 back to contents table  SCI2022 Course manual 2024-2025 PBL-Task 3: Population Genetics: adaptation, evolution and highly prevalent diseases A) If there is random mating and no selective pressure at work in a population, then Mendel’s laws tell us that genotype frequencies in that population will remain stable over generations. Darwin, on the other hand, taught us that there will be changes, because there are always selective pressures at work resulting in adaptation, which is the foundation of evolution. Are these two key concepts at odds with each other? Genotype frequencies are not always stable within any given population. For understanding changes in genotype frequencies, fitness-effects of alleles need to be considered. Assume a simple model: only 2 alleles are involved in the causation of the width of the hips of female animals, W and w. Suppose that allele w causes wider hips than allele W. If wider hips enhance the female fitness (e.g. less complications during the delivery), then logically, selection will favor an increase of the w allele frequency relative to that of W in the population. Yet, it will take many generations before all female individuals have the genotype ww, especially when w is a recessive allele. The Hardy and Weinberg theorem unites Darwin’s and Mendel’s rules and enables us to approach population genetics from a mathematical perspective. B) Investigations into the relative fitness of genotypes reveals that populations can respond to selection in different ways. Two of such responses are depicted in the figure. Genetic diseases with severe effects that are due to a dominant mutation generally occur at very low frequencies in populations. Diseases due to recessive mutations occur at somewhat higher frequencies, but are still very rare. However, some severe recessive genetic disease (allele)s are conspicuously frequent, so that, in addition to mutation–selection equilibrium, yet another explanation is required. One example is Tay-Sachs disease which is strikingly common among descendants from East-European Jews (Ashkenazim): up to 11% of these people (many of whom nowadays are living in the USA) carry a copy of the mutation. Tay-Sachs disease is due to an enzyme deficiency and causes brain degeneration, paralysis, blindness, and death by age four. A second example is CF, Cystic Fibrosis, another recessive disease. Early descriptions of CF mention the most seemingly benign of the symptoms – salty sweat. In fact, in 17th century England people had a saying: “Woe to the child which when kissed on the forehead tastes salty. He is bewitched and soon must die”. CF is characterized by defects in channels leading from certain glands, causing a variety of problems: extremely thick mucus and resulting infections in the lungs; a clogged pancreas and indeed salty sweat. As recently as 1960, a CF patient rarely lived past ten years of age. Today, better treatments may extend the lifetime to 30, sometimes 40 years. The remarkably high frequency (1:50) of the recessive mutation responsible for CF is in European populations puzzles geneticists. 17 back to contents table  SCI2022 Course manual 2024-2025 Exercises/homework: Hardy-Weinberg equilibrium & allele frequencies (1) In some populations, approximately 8% of the men have a particular type of color blindness (an X- linked recessive trait). What proportion of women would you expect to have this trait? What proportion of women would you expect to be carriers for this allele? (2) A plant population has 289 individuals, some bearing red flowers, others white flowers. The red allele is dominant over the white allele. 246 plants have red flowers. Assuming the population is in Hardy- Weinberg equilibrium: a) What is the frequency of the white allele? b) How many of the red plants are expected to be heterozygous? (3) Calculate the frequency of alleles A and B for the following three populations: AA AB BB Population 1 20 40 40 Population 2 30 8 12 Population 3 72 122 91 What are the Hardy-Weinberg frequencies and expected genotypic numbers for the three populations? Are the observed frequencies of the genotypes different from the expected ones? (4) The prevalence of autism is estimated to be 1 per 1000. a. If a single dominant allele caused autism, what would the allele frequency of this allele be? b. What would the frequency of the allele be if autism was caused by a recessive gene? What proportion of the population would be carriers if a recessive gene caused autism? c. If autism is caused by two equally prevalent recessive alleles, what would be the frequency of each of those alleles? Extra: What is then the chance of being a carrier of at least one risk allele? Extra: What is the chance of having a risk allele in the genome in this population? Required literature PBL-task 3:  Zimmer, C. & Emlen, D.J. (2020) Evolution, making sense of Life, 3rd edition, Robertson & Company, Greenwood Village, CO, USA (Chapter 2.1-4; Chapter 6.1-7; Chapter 7.1-5) 18 back to contents table  SCI2022 Course manual 2024-2025 PBL-Task 4: Early genomic conflicts & solutions: endosymbiosis and multicellularity Ever since life started on planet Earth, evolution has led to an increased complexity of life forms. A number of major evolutionary transitions have occurred when life (biosis) evolved from abiosis: simple, self- replicating molecules became cells and ultimately complex, multicellular organisms living in groups or societies. Two examples are (1) the transition from unicellular chronocytes (a.k.a. protoblasts) to the first eukaryotic-like cells, a process summarized in the Endosymbiosis theory and (2) the transition from single to multi-cellular organisms. These ultimate explanations show that transitions may involve related or unrelated species (1): recall that mitochondria, which as a result of endosymbiosis have become cell organelles of the eukaryotic cell, were originally free-living bacteria. In the case of onset of eukaryotic life forms, cooperation was beneficial because two different functions were combined in a new symbiotic replicating unit. The emergence of multi-cellular organisms resulted in a hierarchy of replicating units: individual organisms, cells and cell organelles. However, since all replicating units are subject to adaptive evolution, both endosymbiosis and multicellularity led to challenges at the genetic level (genomic conflicts), that had to be solved. Since the genomes of the chronocyte and the mitochondrion were originally unrelated, genetic conflicts (resulting from non-cooperative behavior) between mitochondria and their host cell were a potential threat. This problem was solved by exchange of genes between the nucleus and mitochondria. Uniparental inheritance of mitochondria solved another potential genomic conflict. At first glance, the risk for genomic conflict in a multicellular organism would appear limited, as all cells in the organism are derived, via mitosis, from of a single fertilized oocyte. Yet, to be able to function as a genetically uniform, complex organisms, harboring multiple specialized tissues and organs, several novel, potential genomic challenges had to be resolved. The use of DNA in basic processes during development and tissue maintenance/repair, including transcription and replication, inadvertently causes DNA damage. At the basis of this is the fact that, in order to fit nearly 2 meters of DNA molecule into a eukaryotic nucleus with a diameter of merely 2 µm, DNA is very tightly coiled-up and condensed. Gaining access to free DNA is complex and intricately regulated at the epigenetic level. Since each cell has only one nuclear DNA template, major DNA-templated processes have become separated in time. Without heavy investment in faithful DNA- repair mechanisms, eukaryotic cells would be doomed to severe genomic conflict from the first cell division onward. In fact, modern-day complex, multi-cellular ‘higher’ organisms would very likely not exist without it. Cancer is an acquired form of genomic conflict; Darwin’s concept of adaptive evolution is extreme in this case. Can you offer proximate and ultimate explanations for this? 19 back to contents table  SCI2022 Course manual 2024-2025 Required literature PBL-task 4:  Zimmer, C. & Emlen, D.J. (2020) Evolution, making sense of Life, 3rd edition, Robertson & Company, Greenwood Village, CO, USA (Chapter 2;); ; Chapter 15.4-5; Chapter 18.7-10).  Campbell, N.A. et al. (2018) Biology, a global approach, 11th edition, Pearson, 330 Hudson Street, New York, NY 10013, SUA (Chapters 7.1-7.8 & 28.1; Chapters 12.2-12.3; 16.2; 17.2, & 17.5; 18.2-18.5) https://library.maastrichtuniversity.nl/resources/libsearch/  Trigos, A.S. et al. (2018) How the evolution of multicellularity set the stage for cancer. BJC 118. https://doi.org/10.1038/bjc.2017.398  Life’s major events - https://www.youtube.com/watch?v=VUfNEHl44hc  RNA-first Video clips: o https://www.youtube.com/watch?v=VYQQD0KNOis o https://www.youtube.com/watch?v=K1xnYFCZ9Yg o https://www.youtube.com/watch?v=yTxZXkp-6sI  Sadler, K.C. (2023) Epigenetics across the evolutionary tree: New paradigms from non-model animals. BioEssays, 45, e2200036. (45) https://doi.org/10.1002/bies.202200036 20 back to contents table  SCI2022 Course manual 2024-2025 PBL-Task 5: Speciation and phylogenetic trees Literally, the word species means ‘kinds’, but this definition hardly contributes to our understanding of what species are. Up until recently, species were mainly distinguished and described based on their appearances. Imagine, however, explaining the difference between a Spider monkey and a Rhesus monkey. Such descriptions do not say much about speciation, i.e. how different species originate. Speciation is known to only happen if so-called isolating barriers are in place, but this term is awfully vague. Is speciation fully understandable in terms of the microevolutionary processes we discussed earlier in this course, or are additional macroevolutionary processes necessary to understand the patterns observed in the fossil record? As indicated by the title of Darwin’s famous book ‘On the Origin of Species’, he put forward the idea that species were not created by a Higher Entity, but instead, that species evolved. Starting from simple life forms, more complex life forms gradually came into being. This process is often depicted as an evolutionary or phylogenetic tree. Darwin’s model of gradual change made sense, although fossil evidence for this model was lacking for most species. More than a century after Darwin’s publications, paleontologists Stephan Jay Gould and Niles Eldredge contested the traditional view of gradual change. They recognized the importance of vast stretches of stasis observed for the majority of species with a fossil record. Gould and Eldredge disagreed with this explanation and recognized the fact that “stasis is data”; based on this, they proposed a new model of evolution: punctuated equilibrium. Phylogenetic trees are constructed based on available data for that part of the tree (e.g. fossils, or molecular data). Oftentimes, especially for branches that lead to extinct species, the data are inconclusive, which leads to construction of so-called consensus trees based on the principle of parsimony. Molecular genetics enable us to construct phylogenetic trees far more precisely. The use of molecular genetic data resulted in essential updates of phylogenetic trees. Required literature PBL-task 5:  Zimmer, C. & Emlen, D.J.(2020) Evolution, making sense of Life, 3 rd edition, Robertson & Company, Greenwood Village, CO, USA (Chapter 4: 4.1, 4.2, & 4.3; Chapter 9.1-10; chapter 13: 13.1, 13.2, & 13.1-3; chapter 14: 14.1- 2, and 14.5). 21 back to contents table  SCI2022 Course manual 2024-2025 PBL-Task 6: Coevolution Throughout the complex history of life, countless adaptations have occurred during coevolutionary interactions. So-called reciprocal selection is the critical prerequisite of coevolution. This selection type varies in its strength and direction within the different populations of species. An example of the difference in strength of reciprocal selection is the Drosophila melanogaster, the common fruit fly, and its evolutionary arms race with a parasitoid wasp. These wasps insert their eggs in their living victims, while the flies have a defense mechanism by encapsulating the wasp eggs. It turns out that there are large geographical differences in efficiency of parasitism by the wasps: in some areas, the wasps are more successful in overcoming the encapsulation and grow anyway. Both species show variation in their coevolved traits; however, the enhanced ability to form an encapsulation response by fly larvae comes with a trade-off, as it causes a reduced competitive ability (see figure 1 and 2 below). A second example of reciprocal selection, called frequency-dependent selection, can be both positive and negative. Positive frequency-dependent selection is often observed in mutualistic coevolutionary relationships, where both species increase their fitness by engaging in the mutualistic relationship. Highly mutualistic species, however, have also been shown to be vulnerable to extinction because of their dependence to each other. Negative frequency- dependent selection can be seen in host-pathogen interactions. In the example on the next page, the fitness of rare bacterial genotypes changes after 22 back to contents table  SCI2022 Course manual 2024-2025 their host (humans) has developed a defense strategy (e.g. a vaccine) that targets the more common genotype. A last example of coevolution is the occurrence of Batesian and Müllerian mimicry. An interesting phenomenon called introgression, as observed in butterfly species, allows certain traits to spread from one species to another via fertile hybrids. Required literature PBL-task 6:  Zimmer, C. & Emlen, D.J.(2020) Evolution, making sense of Life, 3rd edition, Robertson & Company, Greenwood Village, CO, USA (Chapter 15, Chapter 18: 18.1, 18.2, & 18.3)  Kronforst MR (2012) Mimetic Butterflies Introgress to Impress. PLoS Genet 8(6) https://doi.org/10.1371/journal.pgen.1002802 23 back to contents table  SCI2022 Course manual 2024-2025 PBL-Task 7: Sex and sexual selection Sexual reproduction with meiosis and recombination arose 1.5-2.0 billion years ago; before this time, reproduction happened only asexually. The first sexual organisms produced gametes of equal size (called two mating types). However, differentiation in size of the gametes was the first step in the differentiation in sexes. It resulted in large egg cells that were produced in small numbers, and small sperm cells that were produced in large numbers. Now, two key principles of sexual selection came into play. Firstly, egg cells became expensive, while sperm cells became cheap. Furthermore, the limits to the fitness of females and males became different. Given these two principles, the primary and secondary sexual characters evolved. Sex has its advantages, but also comes with disadvantages. Let’s consider the life history of the cecidomyian gall midge, a fly species that has evolved to use the best of both worlds. These mushroom- eating insects reproduce sexually, with flying adults exploring the environment until a mushroom is found. Having located this superabundant food source, the flies can switch to an intriguing, asexual reproduction pathway (called parthenogenesis) where female flies only produce daughters. Although parthenogenesis is quite common, the parthenogenetic descendants of this particular fly never become normal, adult flies, but instead reproduce while they themselves are still larvae or pupae. Furthermore, this fly will not lay eggs, but the descendants develop live within the mother’s tissues, eventually filling up her entire body and devouring her from the inside out. Within two days after hatching from their mothers’ remains, their own developing children are beginning to eat them up. Research has shown that as the abundance of food diminishes, all male and mixed broods develop, while if female larvae have no food at all, the larvae will develop into normal flies. In evolution, the appearance of different sexes indeed redefined fitness of individuals within the same population. Sexual selection came into play, which resulted in both selective pressures between the sexes and within the sexes. Required literature PBL-task 7:  Zimmer, C. & Emlen, D.J.(2020) Evolution, making sense of Life, 3 rd edition, Robertson & Company, Greenwood Village, CO, USA (Chapter 5: 5.5, Chapter 11)  Campbell, N.A. et al. (2018) Biology, a global approach, 11th edition, Pearson, 330 Hudson Street, New York, NY 10013, SUA (Chapter 45.1) https://library.maastrichtuniversity.nl/resources/libsearch/ 24 back to contents table  SCI2022 Course manual 2024-2025 PBL-Task 8: Inclusive fitness theory and cooperation An interesting extension of Darwin’s theory by William Donald Hamilton is called inclusive fitness theory. This extension is important for understanding social behavior. Making use of the principles of game theory, with strategies and outcomes, Hamilton distinguished four types of social interactions (see: figure at the right), based on the pay-off scheme for both players. Depending on the strategy choice of the two players, these pay-offs will have positive of negative fitness effects on the actors. The four types of interactions are mutual benefit, selfishness, altruism and spite. Selfishness and mutual benefit are abundant in nature. Spite rarely occurs (or is absent) for obvious reasons. Altruism, however, also occurs at a high frequency. For example, a parent may jump in a dangerous river to save his or her child. Prairie dogs call out to warn others about the presence of a predator, even if this puts themselves in danger (drawing attention). However, altruism is not easy to understand in terms of Darwin’s original theory because it is costly for the actor. Consider the example of sterile workers helping the queen in eusocial insects. This helping behavior is an obvious example of altruism, but why was this behaviour it selected? 25 back to contents table  SCI2022 Course manual 2024-2025 Another curious phenomenon is that humans are very sensitive to being observed by others. It was noticed by psychologists that humans are more likely to cooperate and to behave socially when they believe they are being watched by others. Even the presence of images of eyes affects their behavior, as one study on the willingness to contribution to a good public cause showed (see figure below). Exercises: (1) What is the generic relatedness between a mother and her child, between two half-brothers, and between two brothers? (2) John Haldane, a famous geneticist and evolutionary biologist, once said: ‘I would sacrifice my life for two brothers or eight cousins’. How can we understand his saying? (3) In haploid-diploid species (such as bees), male individuals are haploid and female individuals diploid. The reason is that females come from fertilized eggs and males from unfertilized eggs. What is, in this system, the genetic relatedness between two sisters, and between a sister and her brother? Required literature PBL-task 8:  Zimmer, C. & Emlen, D.J.(2020) Evolution, making sense of Life, 3 rd edition, Robertson & Company, Greenwood Village, CO, USA (Chapter 16: 16.6, 16.7, & 16.8)  Kurzban, R, Burton-Chellew, M.N. & West, S.A. (2015) The evolution of altruism in humans, Annu. Rev. Psychol. 2015. 66:575–99 https://doi.org/10.1146/annurev-psych-010814-015355 26 back to contents table  SCI2022 Course manual 2024-2025 PBL-Task 9: Placental battles: parent-parent and parent-offspring conflicts The most important extension of Darwin’s theory, as we have seen, is William Donald Hamilton’s inclusive fitness theory. Robert Trivers, following Hamilton’s logic, argued that this theory also explains conflicts between parents and their offspring. Trivers provided an ultimate explanation for this parent-offspring conflict: because of fitness-advantages, mothers favor a shorter period of breast-feeding, whereas neonates favor a longer period. Another example is that in placental mammals, growing fetuses favor high in utero transfer of nutrients from the mother. Hamilton’s inclusive fitness theory explains cooperation in terms of direct and indirect fitness benefits. However, the theory also predicts the evolution of free riders and cheaters. An example is the following: In species such as mice that huddle during the pre-weaning stage, heat production (as the result of burning brown fat) by one individual reduces the heating costs of other individuals. An individual’s heat production is therefore beneficial for the other individuals in a litter. The heat produced may be seen as a collective good that increases inclusive fitness. Free riders are individuals that benefit from the heat produced by others but do not contribute to the common good. Interestingly, the paternal allele involved in heat production in offspring of mice is switched off, while the maternal allele is active. In cases of monogamy, fathers and mothers have the same interests in investing in offspring. In all other cases, however, parental interests can be in conflict. Such conflicting interests concern, among other things, the growth of offspring in utero. This is the case for all Eutherian species. The latter is illustrated by the following experiment. Of the two mouse species Peromyscus polionotus and P. maniculatus, the former species is monogamous, whereas the second species is promiscuous. The body weights of offspring from the two species are similar. However, if a male of the promiscuous species is crossed with a female of the monogamous species, the body weights of the offspring are significantly higher. Conversely, a cross between a female of the promiscuous species and a monogamous male, the body weights of the pups are significantly lower. Genomic imprinting, a so-called epigenetic construct (a mammals-specific, evolutionarily-fixed developmental mechanism), provides a proximate explanation for the above phenomenon. Parentally- biased, allele-specific gene expression is at the basis of the imprinting, and was proposed by Haig and Wilkins as the ‘molecular version’ of this parental conflict: the pro-growth effect of paternally expressed genes is countered by maternal genes. An example thereof is found in the combination of the Igf2 and Igf2R genes. Both genes are imprinted; at the 27 back to contents table  SCI2022 Course manual 2024-2025 protein/cellular level, the maternal IGF2R protein neutralizes IGF2 function (paternally produced IGF2 is internalized upon sequestering by IGF2R, and degraded in lysosomes before it can exert a physiological effect). Molecular genetic experiments, targeted at disrupting either parental allele, support the idea of parent-of-origin effects. Human genetic imprinting conditions, like the Silver-Russell, Angelman, Prader- Willi, and Beckwith Wiedemann syndromes provide further evidence for such parent-of-origin mechanisms in humans as well. Required literature PBL-task 9:  Zimmer, C. & Emlen, D.J. (2020) Evolution, making sense of Life, 3rd edition, Robertson & Company, Greenwood Village, CO, USA (Chapter 12.4).  Constancia, M., Kelsey, G. & Reik, W. (2004) Resourceful imprinting, Nature (432) 53-57 https://doi.org/10.1038/432053a  Renfree, M.B., Suzuki, S. and Kaneko-Ishino, T. (2019) The origin and evolution of genomic imprinting and viviparity in mammals. Phil Trans R Soc B (368) 20120151 https://doi.org/10.1098/rstb.2012.0151 28 back to contents table  SCI2022 Course manual 2024-2025 PBL-Task 10: What makes humans (typically) human? Over the course of evolution, the human brain has dramatically increased in size: our brains are much larger compared to those of our closest living relative, the chimpanzee. At the same time, our cognitive functions (e.g. intelligence) have gone beyond those of for example chimpanzees, as well. On the other hand, blue whales have a much larger brain than humans do, so why were they not the ones that have such extensive cultural and technological inventions? In order to understand what is special about human behaviour and psychology, we need to understand the evolutionary history of our brains and the resulting increase in cognitive functions. Explaining the evolution of cognition is not an easy undertaking. One can compare this task to that of a detective showing up at a crime scene after the fact, and having to reconstruct past events based on the current situation. Similarly, an evolutionary detective has to use many such clues to reconstruct a coherent theory on why our brain evolved the way it did. Have a look at some of the evidence found at the crime scene: Clue 1: A human brain is energy expensive: the brain requires ca. 22% of our resting metabolic rate, while it only accounts for 2% of body mass. Chimpanzee brains only require about 8%. Clue 2: At some point in human evolution, our ancestor’s tool-use increased rapidly. Clue 3: Humans are the only species who evolved language ability, and a sophisticated mind-reading ability (theory of mind). Clue 4: At some point during the Paleolithic period, the Old Stone Age, humans started to live in increasingly larger groups. Clue 5 on next page! 29 back to contents table  SCI2022 Course manual 2024-2025 Clue 5: When comparing young human infants with the chimpanzee and orangutan, it appears that human infants especially outperform other apes on intelligence tasks in the social domain – solving a simple, yet not obvious, problem by observing and learning from a demonstrated solution. However, this superiority is not observable in the physical domain – for example, tracking of a reward after its location changes. Required literature PBL-task 10:  Zimmer, C. & Emlen, D.J.(2020) Evolution, making sense of Life, 3 rd edition, Robertson & Company, Greenwood Village, CO, USA (Chapter 16.1 & 16.9; chapter 17.1 & 17.10-11)  Dunbar, R.I.M. & Shultz, S. (2007) Evolution in the social brain, Science , Sep. 7, 2007, New Series, Vol. 317, No. 5843 (Sep. 7, 2007), pp. 1344-1347 https://doi.org/10.1126/science.1145463  Van Schaik et al (2012) Explaining brain size variation: from social to cultural brain, Trends in Cognitive Sciences, May 2012, Vol. 16, No. 5, pp 277-284 https://doi.org/10.1016/j.tics.2012.04.004  https://www.science.org/content/article/fruit-eating-responsible-big-brains  https://www.theguardian.com/science/2015/feb/26/gene-that-makes-human-brain-unique-identified-by- scientists Available via Canvas (Modules  Literature)  DeCasien et al (2017) Primate brain size is predicted by diet but not sociality, Nat. Ecol. Evol. 1, 0112 https://doi.org/10.1038/s41559-017-0112  Cartwright, J. Evolution and Human Behavior (2008). Third Edition. Cambridge: MIT press (Chapter 6: 6.3) 30 back to contents table  SCI2022 Course manual 2024-2025 Appendix I: Additional literature list per PBL task The list below provides you with interesting and useful context per task. Please note that watching/reading these is not mandatory - only the literature mentioned at the end of each task is required for the exam. Several online lectures on evolution exist, among which lectures by a professor at Yale University. Watching these ±45 min lectures may be useful to prepare for the PBL-tasks. Yale Courses: Stephen C. Stearns – https://www.youtube.com/playlist?list=PL6299F3195349CCDA PBL-Task 1 - MENDELIAN RULES AND EXCEPTIONS YaleCourses: Stephen C. Stearns – https://www.youtube.com/playlist?list=PL6299F3195349CCDA 1.-The Nature of Evolution: Selection, Inheritance, and History; (principles in evolution) 2.-Basic Transmission Genetics (DNA, RNA, protein, mitosis, meiosis) PBL-Task 2 - ORIGINS AND EDITIONS OF THE BOOK OF LIFE YaleCourses: Stephen C. Stearns – https://www.youtube.com/playlist?list=PL6299F3195349CCDA 1.-The Nature of Evolution: Selection, Inheritance, and History; (principles in evolution) 2.-Basic Transmission Genetics (DNA, RNA, protein, mitosis, meiosis) PBL-Task 3 - POPULATION GENETICS: ADAPTATION, EVOLUTION AND HIGHLY PREVALENT DISEASES YaleCourses: Stephen C. Stearns – https://www.youtube.com/playlist?list=PL6299F3195349CCDA 4.-Neutral Evolution: Genetic Drift 5.-How Selection Changes the Genetic Composition of Population 6.-The Origin and Maintenance of Genetic Variation 7.-The Importance of Development in Evolution PBL-Task 4 - EARLY EVOLUTIONARY TRANSITIONS II AND GENOMIC CONFLICTS YaleCourses: Stephen C. Stearns – https://www.youtube.com/playlist?list=PL6299F3195349CCDA 17.-Key Events in Evolution 18.-Major Events in the Geological Theatre 10.-Genomic conflict (only the first 20 minutes) PBL-Task 5 - SPECIATION AND PHYLOGENETIC TREES YaleCourses: Stephen C. Stearns – https://www.youtube.com/playlist?list=PL6299F3195349CCDA 11.-Life History Evolution 14.-Species and Speciation 15.-Phylogeny and Systematics 16.-Comparative Methods: Trees, Maps, and Traits PBL-Task 6 - COEVOLUTION YaleCourses: Stephen C. Stearns – https://www.youtube.com/playlist?list=PL6299F3195349CCDA 20.-Coevolution 1.-The Nature of Evolution: Selection, Inheritance, and History; (principles in evolution) 3.-Adaptive Evolution: Natural Selection 4.-Neutral Evolution: Genetic Drift 31 back to contents table  SCI2022 Course manual 2024-2025 PBL-Task 7 - SEX AND SEXUAL SELECTION YaleCourses: Stephen C. Stearns – https://www.youtube.com/playlist?list=PL6299F3195349CCDA 9.-The Evolution of Sex 10.-Genomic Conflict 12.-Sex Allocation 13.-Sexual Selection PBL-Task 8 - INCLUSIVE FITNESS THEORY AND COOPERATION YaleCourses: Stephen C. Stearns – https://www.youtube.com/playlist?list=PL6299F3195349CCDA 32.-Economic Decisions for the Foraging Individual 33.-Evolutionary Game Theory: Fighting and Contests 34.-Mating Systems and Parental Care 35.-Alternative Breeding Strategies 36.-Selfishness and Altruism PBL-Task 9 - PLACENTAL BATTLES: PARENT-PARENT AND PARENT-OFFSPRING CONFLICTS YaleCourses: Stephen C. Stearns – https://www.youtube.com/playlist?list=PL6299F3195349CCDA 9. The Evolution of Sex 10. Genomic Conflict 12. Sex Allocation 13. Sexual Selection PBL-Task 10 - WHAT MAKES HUMANS (TYPICALLY) HUMAN?  Evolution of the Human Brain: https://www.youtube.com/watch?v=zpVuYns9ulo  Genes, Cognition, and Human Brain Evolution: https://www.youtube.com/watch?v=tN1Bc-WT0oQ  Foxp2/Language: https://en.wikipedia.org/wiki/FOXP2 32 back to contents table  SCI2022 Course manual 2024-2025 Appendix II: Presentation assignment Suggestions for the organization of your presentation Start the presentation with a brief introduction/background on the topic that you are going to discuss. Explain why it is interesting to undertake an evolutionary analysis of the topic. Which aspects of the topic can be clarified with the help of evolutionary theory? In a separate section, explain what evolution is, what evolutionary explanations are (including the difference between ultimate causal and proximate causal explanations), and the evolutionary background and/or explanations relevant to your topic. In the overview section, you discuss the design and results of the empirical research relevant to your topic. What research question was central to the research? What hypotheses were tested? What methods/models were used? What were the results? Finally, you should discuss the specific problem raised in the introduction to your report. What answer(s) (conclusion) can be provided to the problem? What suggestions can you make on the basis of your analysis for future research? Example One example is the topic of “a fear of snakes” or a snake phobia. At first glance, this phobia appears to be a “deviation” rather than an evolutionary adaptation. In the introduction, this can be formulated as a specific problem. Is a fear for snakes a deviation or an adaptation? In addition, you can explain why it could be an adaptation. The different arguments for such a position can be presented. First, the fear has avoidance of snakes as a consequence and thus reduces the risk of deadly snake bites. In this sense, the fear actually increases the chances of survival. Second, empirical research shows that people develop phobias for only things that are dangerous (thus for snakes and not tea cups). This empirical data also points to adaptation. The proximate cause of the adaptation is certain environmental stimuli (“smooth and slippery animals”) that elicit the avoidance reaction; the ultimate cause of the adaptation is that people who develop a fear of certain animals have greater chances of survival than those who do not. The question for further research is why some people have a more or less simple fear of spiders or snakes while others develop a more excessive fear? 33 back to contents table  SCI2022 Course manual 2024-2025 Assignment topics - examples I - Genetics & Evolution One way to study genetics is to study a specific topic. Below some topics are suggested below, but you are allowed to choose a topic yourselves. Potential topics: o Evolution and the genetics of viruses o Evolution and DNA Repair o Evolution and mutations (chromosomal and/or point mutations) o Evolution and recombination o Evolution and genetics of mitochondria o Evolution of Sex determination o Evolution of X-inactivation o Evolution and genomic imprinting o Evolution and quantitative genetics o Evolution and the genetics of the immune system o Evolution and non-coding RNAs o Evolution of epigenetic regulation Another way to study genetics is to study a disease with a genetic cause. Through studying an (abnormal) disorder that is caused by a genetic mutation, you will get a clearer picture of the role of genes is the ‘normal’ development. The best way to start is to use internet sites. Two sites that deal with genetics and diseases are: http://www.geneclinics.org http://www.ncbi.nlm.nih.gov/ The second site allows you to enter OMIM (Online Mendelian Inheritance in Man). Both sites give you the opportunity to obtain information about the genetic background of several diseases. Some diseases which can be linked to genetics and evolution are: o Rett syndrome o Autism o Obesitas o Anorexia nervosa o Prader-Willi syndrome, Angelman syndrome o Turner syndrome, Klinefelter Syndrome o Schizophrenia o Dyslexia o ADHD o Dementia o Williams syndrome o Chromatinopathies o Hemochromatosis o Cancer 34 back to contents table  SCI2022 Course manual 2024-2025 II - Evolutionary Biology, Medicine and Psychology It is interesting to apply evolutionary theory to a specific topic and answer the question what an evolutionary approach adds to understanding the topic. Some topics are mentioned below, but you are free to choose a topic yourself. Potential topics: Child Abuse  D.M. Buss, Evolutionary psychology, Allyn and Bacon, Boston, 1999 (chapter 7). Evolution of Ageing and/or Menopause  Nesse, R.M. & Williams, G.C., (1994) Why we get sick, New York (Chapter 8).  Austad, S.N., (1997), Why we age, John Wiley, New York (Chapter 7 and 9).  Barrett, L., Dunbar R., Lycett, J. (2002), Human evolutionary psychology, Palgrave NewYork (Chapter 6).  Irizar, P.A. et al. (2018) Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly. Nature Communications. DOI: 10.1038/s41467-017-02395-2.  Kirkwood, T.B.L. (2002), ‘The evolution of ageing’, Mechanism of aging and development, 123, 735-745.  Kirkwood, T.B.L. & Austad, S.N. (2000) why do we age? Nature, 408, 233-238.  S.C. Stearns & R.F. Hoekstra (2005), Evolution; An introduction, Oxford University Press, Oxford (Chapter 10; especially 230-236).  Laurent, J.N. et al. (2015) Ecological Knowledge, Leadership, and the Evolution of Menopause in Killer Whales. Current Biology. 25: 746-750.  Ricklefs, R.F. & Finch, C.E., (1995), Aging; A natural history, Scientific American Library, New York (Chapters 6 & 7).  Rusting, R.L., (1992) 'Why do we age?', Scientific American, 267(6), 87-95.  Sherman, P.W., (1998), 'The evolution of menopause', Nature, 392, 759-761; and Packer, C., Tatar, M. & Collins, A., (1998), 'Reproductive cessation in female mammals', Nature, 392, 807-810. Evolution of Cooperation, game theory  Axelrod, R., (1984), The evolution of Cooperation, Basic Books Inc., 1984 (Chapter 4).  Badcock, C., Evolutionary psychology; A critical introduction, Polity, Oxford, 2000 (Chapter 3).  Barrett, L., Dunbar R. & Lycett, J. (2002), Human evolutionary psychology, Palgrave NewYork (Chapter 2 & 3).  Buss, D. (1999), Evolutionary Psychology. The new science of the mind, Allyn and Bacon, Boston (Chpt 9).  Dawkins, R. (1998), The selfish gene, Oxford U.P., Oxoford, 2e druk (Chapters 5 & 12).  Faurie, C. and Raymond, M. (2005) Handedness, homicide and negative frequency-dependent selection.  Proceedings of the Royal Society B. 272: 25-28  Maynard Smith, J. (1989), Evolutionary genetics, Oxford university press: Oxford, 1th edition (Chpt 7).  Nettle, D. (2009) Evolution and genetics for psychology. Oxford: Oxford University Press (Chapter 8)  Nowak, M.A. & Sigmund, K. (2005) Evolution of indirect reciprocity, Nature, 437, 1291-1298.  Smit, H, (2018) Game theory: finding the ESS, Maastricht University. Online videos: Prisoner’s dilemma:  https://www.youtube.com/watch?v=t9Lo2fgxWHw&t=126s (first two minutes)  https://www.youtube.com/watch?v=BOvAbjfJ0x 35 back to contents table  SCI2022 Course manual 2024-2025 Evolution of homosexuality  LeVay, S. & Hamer, D.H. (1994) Evidence for a biological influence in male homosexuality, Scientific American, Mmay, 20-25.  Camperio-Ciani, A., Corna, F. & Capiluppi, C. (2004) Evidence for maternally inherited factors favouring male homosexuality and promoting female fecundity, Proceedings of the Royal Society B, 271, 2217-21.  G.A. Schuiling, (2004), Death in Venice: the homosexuality enigma, Journal of Psychosomatic Obstetery and Gynaecology, 25, 67-76. Evolution of language  Hauser, M.D., Chomsky, N. & Fitch, W.T. (2002), The faculty of language: what is it, who has it, and how did it evolve?, Science, 298, 1569-1579.  Pinker S. & Jackendoff, R. (2005), The faculty of language: what's special about it? (2005), Cognition, 95(2), 201-36. Evolution of warfare  Wrangham, R, (2006), Why apes and humans kill, in M. Jones & A.C. Fabian (eds.), Conflict, Cambridge University Press, Cambridge, 43-62.  Cunlife, B. (2006), The roots of warfare, in: M. Jones & A.C. Fabian (eds.), Conflict, Cambridge University Press, Cambridge, 63-81.  Buss, D.M. (ed.), A handbook of human evolutionary psychology, Wiley, New York, 2005. High frequency of disease alleles in populations  Sickle (malaria, Beduins), LDLR (Somoa), Hemochromatosis, gluten intolerance (North-West Europe). Intragenomic conflict and pregnancy  Haig, D. (1993), ‘Genetic conflicts in human pregnancy’, The Quarterly review of biology, 68, 495-532. Mate choice and disease resistance  Potts, W.K. & Wakeland, E.K., (1993), 'Evolution of MHC genetic diversity: a tale of incest, pestilence and sexual preference', Trends in Genetics, 9, 408-412.  Wedekind, C. et al., (1995), 'MHC-dependent mate preferences in humans', Proceedings of the Royal Society London B, 260, 245-249.  Hill, A.V.S. (1999), 'Defense by diversity', Nature, 398,668-669.  Beauchamp G.K. & Yamazaki, K., (1997), 'HLA and mate selection in humans: commentary', American Journal of Human Genetics, 61, 494-496. Morning sickness  Profet, M. (1992), Pregnancy sickness as adaptation: a deterrent to maternal ingestion of teratogens, in J.H. Barkow, L. Cosmides & J. Tooby (eds), The adapted mind, Oxford University Press, 327-365.  Forbes, S. (2002), ‘Pregnancy sickness and embryo quality’, Trends in Ecology and Evolution, 17, 115- 120.  Flaxman S.M, Sherman P.W. (2008) Morning sickness: adaptive cause or nonadaptive consequence of embryo viability?, The American Naturalist, 172, 54-62. Symmetry and partner choice  Gangestad, S.W. & Thornhill, R. (1997), 'The evolutionary psychology of extrapair sex: The role of fluctuating asymmetry', Evolution and human behavior, 18, 69-88. 36 back to contents table  SCI2022 Course manual 2024-2025 To resemble or not to resemble  Platek, S.M. et al (2002), ‘Reactions to children’s faces resemblance affects males more than females’, Evolution and human behavior, 23, 159-166.  Christenfield, N. & Hill, E. (1995), Whose baby are you?, Nature, 378, 669. Uniparental inheritance of mitochondria  Hoekstra, R.F. (2000), ‘Evolutionary origin and consequences of uniparental mitochondrial inheritance’, Human Reproduction, 15 (suppl 2.), 102-111.  Frank, S.A. & Hurst, L.D. (1996), ‘Mitochondria and male disease’, Nature, 383, 224. Virulence  Ewald, P.W., (1993), 'The evolution of virulence', Scientific American, April, 56-62.  Nesse, R.M. & Williams, G.C., (1994), Why we get sick, New York (Chapter 4).  Lockhart, A.B., Thrall, P.H., & Antonovics, J. (1996), Sexually transmitted diseases in animals: ecological and evolutionary implications', Biological Reviews, 71, 415-419.  Ewald, P.W., (1994), Evolution of infectious disease, Oxford (Chapter 3, 6 & 11). 37 back to contents table  SCI2022 Course manual 2024-2025 APPENDIX III: STUDY SKILLS AND PROBLEM-DIRECTED LEARNING In the following, a summary of the different activities relevant to working in the study group is presented for review during the first meeting of the study group. First meeting of the course Does everyone know each other? Exchange of addresses and telephone numbers. Agree on the order for discussion leadership. The person leading the next discussion is responsible for taking notes on the present discussion. Working with the seven steps during PBL sessions Step 1: Clarification of concepts. In order to avoid misconceptions and misunderstandings, the concepts used in the task are clarified. In such a manner, a joint starting point for discussion is also established. Step 2: Problem formulation. The core of the task is determined in order to further delineate the subject matter. Step 3. Problem analysis/brainstorming. Refreshment and delimitation of the knowledge present in the group (activation of prior knowledge) and thereafter identification of as many explanations, alternatives, and hypotheses relevant to the problem as possible. Step 4. Problem analysis/systematic listing. Ordering of explanations mentioned during brainstorming and establishment of any connections/relations thereafter. Step 5. Formulation of learning objectives. Identify in light of the aforementioned explanations what knowledge is lacking and what issues remain unclear. On the basis of this information, formulate learning objectives. Step 6. Self-study. Acquisition of new information in such a manner that you understand it and can apply it to the relevant learning objectives. In addition, critical reflection on already existing and new knowledge in order to make a link to the preliminary discussions and learning objectives. Such self- study also prepares one for efficient and effective participation in the study groups. Step 7. Reporting. In discussion with one’s fellow students, the answers to the learning objectives are sought and reported on along with any remaining questions or ambiguities. After completion of the final discussion, everyone should know for him/herself whether the new knowledge has been understood, the study materials have been examined in sufficient depth, and whether the new information can be adequately explained to others or not. Report using your own words and not directly from a book. 38 back to contents table  SCI2022 Course manual 2024-2025 Leading a group discussion Preparation. Preparation of an “agenda” provides for effective and efficient discussion. Ask each member what he or she has done and from which book(s). What you could not find should also be clarified. Structuring. Ordering of different contributions, indication of the different lines of discussion, and monitoring of the relevance of the topics being discussed. Summary. An outline with a number of the main points can help structure the meeting, be used to determine whether the material under discussion has been understood or not, and also be used to stimulate discussion by the group members. Stimulation. Getting the meeting started and maintaining order. Posing specific questions helps structure the meeting, stimulate contributions, and promote in-depth consideration during the preliminary and final task discussions. Reformulation. More precise formulation of what a fellow student has said in order to expand the understanding of the group and determine whether what was said by the group leader or another member of the group has been understood. Conclusion. Statement of what has been done, what has been decided, and what has been agreed upon as the starting point for the next meeting. Participation in the study group Note-taking. Provision of an overview and clear depiction of the information exchanged during the study meetings by taking notes and drawing diagrams. Provision of information. Actively telling fellow students what is known during preliminary discussions, reporting on what has been decided and deduced during concluding discussions, and supplementation or clarification of information provided by fellow students. Information requests. Pose precise questions for explanation, clarification, or illustration of information from others and checking or expansion of one’s own information. Summarizing. Statement of the main points can help structure the meeting, stimulate discussion by group members, and aid determination of whether the material under discussion has been understood or not. Active listening. Active evaluation of whether one’s own (new) knowledge and that of one’s fellow students is correct and contributes to a better understanding and better recall of the material. An active listening attitude stimulates both the group process and product. Evaluation Observation. Pay attention to the methods of working, processes, and norms at play in the group. This helps provide insight into the efficiency and efficacy of the meeting. Analysis. On the basis of observations, the positive or negative influence of agreements that have been made (or not made), different procedures, and various behaviors on the course of the meeting should be determined. Provision of feedback. Inform each other of any observations, irritations, or opinions in order to adjust the objectives of the group accordingly, produce better cooperation, and deepen the discussion. 39 back to contents table  SCI2022 Course manual 2024-2025 Science code & Plagiarism, AI-text tools Science is a profession in which professional integrity is required at the highest level. Everyone is expected to act in the most truthful manner. This concerns, among other things, collegiality, neutrality, openness and honesty. To this end, the VSNU (Association of Cooperating Dutch Universities) has drawn up a code of conduct that every employee is expected to know. Students should take note of this and orient themselves, behave accordingly and aim for proficiency, also during their studies. The code of conduct can be found on the VSNU website: http://www.vsnu.nl/files/documents/Domeinen/Onderzoek/Code_wetenschappenbepraktijk_2004_(2012).pdf All assignments in this course are submitted via Safe Assign. N.b. the software in Canvas screens for plagiarism. Plagiarism is a criminal offence. Use of AI in this course will be viewed as “commissioned work” and is for this reason not allowed. Suspicion of plagiarism and/or illegitimate use of AI will be immediately reported to the Board of Examiners (BoE) for assessment. Determination of plagiarism by the BoE may lead to exclusion from examinations for a certain period of time, or to retroactive invalidation of the diploma. 40 back to contents table