MBIO3430: Molecular Evolution, Fungi & Genomics

• Molecular evolution refers to the evolutionary processes at the scale of DNA, RNA, and proteins.

Origin of Georg Hausner (G.H.)

• Georg Hausner's research focuses on mitochondrial genetics and genomics of fungi, molecular biology, applied bioinformatics, and the evolution of mobile elements and ribozymes.
• His work involves the evolution of fungal mitochondrial genomes and their mobile elements.
• G.H.'s research examines self-splicing ribozymes and homing endonucleases.

Course Description

• The course, MBIO3430 Molecular Evolution, delves into the molecular evolution of biochemical processes, genomes, and phylogenetics.
• It also explores applications in medicine, biotechnology, anthropology, biology, and history.
• The prerequisite for this course is one of MBIO 2020, (=MBIO 2110).
• Molecular Biology 3410 is highly recommended.
• Students must check UMlearn Announcements for updates regarding the course.
• All course materials, including lecture materials, are available on UMlearn.
• Misuse of course material may result in removal from the course site.
• All course materials belong to the University of Manitoba and/or the instructor, and are for personal use only.
• Students are not allowed to post/share the material with other people or sites.
• Recording lectures without the instructor's permission is prohibited.

Course Topics

• Evolution of the HIV virus, Bird Flu, Covid-19, and antibiotic resistance are part of the introductory topics.
• The course will explore molecular origins of life, from organic molecules to self-replicating systems.
• "Genetic takeover", ribozymes, and the RNA world will be discussed.
• Carl Woese and the three domains of life, including updates to two domains, are included in course material.
• Other topics include changes in nucleotide and amino acid sequences, molecular data, and phylogenetic trees.
• Basic concepts of evolution are studied, such as selection, fitness, modern synthesis, neutral theory of evolution, Evo-Devo, and micro/macro evolution.
• Mechanisms of speciation, gradualism, punctuated evolution, species concept, and molecular mechanisms are covered.
• Concerted evolution and molecular drive within gene families, genomes and their evolution, repetitive/"selfish" DNA, genome expansion, and "new" genes are studied.

Course Material and Evaluation

• The course includes a midterm exam on March 4th, 2025, contributing 30% to the final grade.
• There are two assignments.
• Part 1 must be submitted online by February 14th, 2025, and is worth 5%.
• Part 2 is due on April 4th, 2025, contributing 15%.
• Additionally, there is a final exam, with a contribution of 50% toward the final grade.

Success Tips

• Attending lectures, keeping notes up to date, and organizing information are keys to success.
• Dedicate a few hours a week to the material and put concepts together based on what is being presented.

Learning Objectives

• Learning outcomes for the course include knowing what molecular evolution is and understanding the course overview.
• Students need to know what the difference is between a pandemic and an epidemic.
• Zoonosis and what can be learned from viruses/microbes regarding molecular evolution.
• The course introduces the origin of HIV.
• Studying molecular evolution enables comparisons among different organisms or mechanisms like replication, transcription, and translation.
• Evolution provides a scientific explanation for life (*genetic system/replicons), through the study of Viruses, Archaea, Bacteria, and Eukaryotes.

Applications of Molecular Evolution and Definitions

• Origin of HIV and AIDs, fungal diseases, viral infections, and bacterial infections are examples of molecular evolution applications.
• Acquired immunodeficiency syndrome (AIDS) is a condition caused by HIV.
• A pandemic is defined as an epidemic that spreads across a large region.
• Zoonotic diseases are examples of applications of molecular evolution

Zoonotic Diseases

• Zoonotic diseases can be transmitted from animals to humans.
• An estimated 75% of newly emerging diseases are zoonoses, and 60% of infectious diseases in humans are spread from animals.
• Zoonotic diseases account for 2.5 billion cases of illness and 2.7 million deaths worldwide each year.
• The course provides zoonosis examples such as E. coli O157:H7 from domesticated animals like cattle, and swine/bird flu from domesticated birds or pigs.
• Food-borne illnesses, and cryptosporidiosis.
• COVID-19 (raccoon/dogs and bats) and the Ebola virus (bats) are also included in zoonosis.
• Ebola has multiple hosts and modes of transmission, including contact with feces, dead bodies, and consumption of infected animals.
• Zoonosis is defined as an infectious disease of humans caused by a pathogen that jumps from non-human animals.
• Reverse zoonosis occurs when humans infect non-human animals.

Pandemics

• The course includes the history of past and current pandemics, such as cholera, typhoid fever, typhus, and influenza.
• The "Spanish" influenza of 1918/19 killed 50-100 million people worldwide in a few months.
• The "Black Death" bubonic plague killed 28 million in 5 years, which amounted to 30-40% of the population in affected areas.
• Covid-19 has resulted in over 6.9 million deaths as of Dec/2023.
• Smallpox is caused by Variola major and Variola minor, with a zoonotic origin from rodents or herd animals.
• Colonization in 1520 introduced a new pathogen spread by European conquistadors.
• Smallpox decimated North and South American native populations.
• 300 million people have died from smallpox since 1900, but now the disease is extinct due to vaccination.
• There are zoonotic orthopoxviruses such as cowpox (cows, rodents, cats) and monkeypox (monkeys, small mammals) transmitted through close contact.
• Smallpox is transmitted between humans through physical contact and body fluids.
• Topics include Avian flu , H5N1 strains, and Superbugs (antibiotic-resistant bacteria).
• First officially reported in 1981, HIV has caused over 40 million deaths.

Course Modules

• The course modules include HIV & Influenza, and Covid-19 & Superbugs
• Focus is on the origin and evolution of HIV
• There are two types; HIV-1 is the major cause of aids, HIV-2 is less frequent.
• HIV is caused by a Retrovirus, with a DNA genome after infection Viral genome inserted into the host genome.
• SIV - is simian immune deficiency virus.
• Globally an estimated 70 million people have HIV

HIV

• HIV can only enter cells expressing the transmembrane protein CD4 and coreceptors like CCR5 or CXCR4.
• The virion binds to CD4 and a co-receptor via its gp120 glycoprotein.
• The genome consists of a very compact, overlapping RNA converted to DNA via reverse transcriptase.
• Integrase inserts the viral genome into the host genome.
• Protease resolves fusion proteins, breaking down fused genes into protein products.
• HIV uses Simian immunodeficiency viruses (SIV) normally hosted by non-human primates without symptoms.
• Single/rare host-jump (monkey to human) and/or independent origins, as well as questions about HIV1/HIV2 subtypes.
• Phylogenetics helps to test hypotheses about where HIV comes from.
• Phylogenetics relies on sequence alignment and analyses evolutionary history.
• You can get sequences for HIV and SIV reverse transcriptases from humans and primates alike

Molecular Evolution: Phylogenetics

• The first step is to acquire data using molecular biology techniques or data mining from databases.
• Secondly sequence alignment through alignment programs.
• Thirdly analyze the data to make inferences about the evolution.
• Phylogenetic trees show related taxa.
• Tree construction programs include MEGA, PAUP, MrBayes, and PHYLIP etc.
• Phylogenetic trees have nodes that suggest a common ancestor.
• Branches indicate genetic distance or rate of change.
• Clades are monophyletic groups sharing recent common ancestors.

HIV Origins

• HIV-1 and HIV-2 have independent origins.
• Also, the HIV1 and HIV2 subtypes can traced using Phylogenetic analysis.
• Human "forms" do not share an ancestor and are SIVcpz/t SIV from chimpanzees.
• Evidence suggests SIVcpz is the ancestor.
• SIVsmm SIV from sooty mangabeys, or Cercocebus atys, is another possible origin.
• Phylogenetic tree studies and molecular evolutionary data showed 20 different species.
• A phylogenetic tree was generated using RT sequence analysis.
• Each group such as (clade HIV1 and HIV2):
• HIV 1 appears to have jumped from chimps to humans on 2 separate occasions.
• New evidence in 2015 suggests that O type has different origin.
• HIV 2 appears to have jumped from sooty mangabeys to humans on at least 3+ different occasions.
• The 2 types of HIV are HIV-1 (M and N) is most closely related to a SIV found in SIVcpz in wild chimpanzees.
• The species is Chimpanzee (Pan troglodytes)

HIV History

• Estimated time transfer to humans started 1908 HIV-1 and for HIV-2 Transfer started around 1920
• HIV-1 humans butcher chimps the virus was carried people travel in Congo, 1920s.
• SIVcpz evolved with Chimps (a specific subspecies) SIVcpz with one prey.
• Red capped monkeys and mona, spot nosed monkey and mixing vessels.
• SIV virus lead for HIV-1 the 1980s, for the 2000s.
• HIV-1 P was founded with Cameroonian woman, and HIV-2 is the gorillas’
• Phylogenetic tree was constructed using RT gene sequences.
• HIV originated through four different lineages.
• HIV1 – four lineages, M, N and O and P.
• And the apes are chimpanzees.

HIV Types and Strains

• HIV-1 group M is the strain responsible for the global pandemic.
• Types N, O, and P are rare but are found in Cameroon, Gabon, and Equatorial Guinea, recently O/M recombinants have been noted.
• The o types account for one percent of the population.

Evolution

• Genotypic changes can influence phenotype, as changes are inevitable.
• Rna / DNA can mutate and this will cause an issue.
• polymerase and mutagens can cause mutations etc.

Genetic Variability Within HIV

• Reverse transcription (RNA -> DNA) lacks proofreading, leading to frequent mutations.
• This causes development of resistance to anti-viral drugs and Complicates development of a vaccine.
• In addition this creates new strains Hiv-1 and Hiv-2 This is also Variability used in forensics
• CRFs –are created due to recombination.

HIV Medications

• Anti-HIV drugs include nucleotide/nucleoside analogs, RT inhibitors, integrase inhibitors, protease inhibitors, and capsid inhibitors.
• Fusion inhibitors (CCR5 antagonists) exist.
• Multi-drug cocktails can keep viral load undetectable, but have side efforts and are expensive.
• Now there are new CRF strains: The CRF can develop in under 3 years
• Current anti-HIV medicines will not effect Progression.

Zoonotic Transfers

• A trim 5 is from humans defense by retro viruses and old world monkeys cannot get hIV easliy.
• The proteins interfere with proper capsid uncoating and RT step.