Panorama of Life Chapter 3 PDF

Panorama of Life Chapter 3: 88-97, 99-101, 104 (Box 3.4), 108-114 1 Topics Genomes numbers and characteristics "Probable" example of evolution by gene duplication Pseudogenes 2 G...

Panorama of Life Chapter 3: 88-97, 99-101, 104 (Box 3.4), 108-114 1 Topics Genomes numbers and characteristics "Probable" example of evolution by gene duplication Pseudogenes 2 Genomes Human cells: 23 pairs of chromosomes (1-22, XX or XY) No simple proportionality between genome size and number of proteins encoded 3 X 109 3 Generalities Metazoa (Animals) have just over 20,000 protein coding genes Biological Kingdom “Animalia” 1.5 million species, including Humans, have been described 1 million species are insects Humans have about 23,000 protein coding genes, and about 100,000 spliced proteins Can be time dependent (e.g., growth of the optic nerve) Can be space (tissue) dependent (e.g., retinal cells have rods/cones, cardiac cells do not) 4 PhiX-174: 10-gene virus Mitochondria hot springs H. Pylori – bacterium causing ulcers Vibrio Cholera 5 Lives in your gut Yeast == beer Similar gene Important makeup as model humans, but organism with much less intergenic sequence Human 6  Understanding of Biological 7 Principles Nervous system development. Neurogenesis. Neuronal migration. Growth cone guidance. Circadian rhythms. Learning and memory. Why study model systems like fruit Nervous system proteins. flies? Synaptic Transmission. Is this a waste of tax-payer money? No! The study of model organisms, such as the fruit fly or yogurt, has led to massive scientific breakthroughs! The Crispr/Cas9 gene editing system was discovered by a US/France collaboration in yogurt. 8 Proteomics A protein inferred from a genome sequence is a hypothetical object until an experiment verifies its existence and measures its properties Post-translational modifications Change behavior from genetic sequence alone Addition of a phosphate by a kinase Addition of sugar – the COVID-19 spike protein Sugar Shield (computer models) 9 Dog Cow GMO? Chicken 10  Estimates of vitamin A deficiency (1991-2013), ages 0-5. Red is most severe (clinical). Stevens GA, et al. PMID: 26275329. Global and Social Awareness 250,000 to 500,000 children become blind every year because of vitamin 11 Golden Rice: GMO'ed to contain beta- carotene, precursor to Vitamin A PNAS:2021 Global and Social Awareness 12  Bangladesh prepares to release GMO golden rice Led by the environmental nonprofit Greenpeace, anti- GMO groups have fought for years to block the introduction of golden rice, claiming it is a ‘Trojan horse’ designed to sneak GMO seeds into countries that don’t want them. This conspiratorial narrative, Novella says, is a dishonest attempt to shift focus away from the science that shows golden rice is safe and effective. https://geneticliteracyproject.org/2019/03/22/podcast-yale-neurologist-steven-novella-debunks-popular-myths-about- 13 gmo-golden-rice/ Science on GMOs -- Global and Social Awareness A 2017 review of studies, essentially two decades after this switch (to GMO animal feed), found: "Based on this literature review, we conclude that there is no clear evidence that feed composed of first generation GM crops has adverse effects on animal health." Literally trillions of animals have been fed with GMO feed without any detectable negative health effect. Switching to non-GMO feed can have negative effects. According to research conducted by Iowa State University, such a change would increase greenhouse gas emissions by 7%, increase land use, and increase the price of food. To date there have been over 3,000 studies looking at the health and environmental safety of GMO crops, without any evidence of harm or a legitimate safety issue. 14 GMOs in Human Foods Modern agriculture has been "mutation breeding" for the last 100 years Chemicals or radiation is used to increase mutations by 1,000 to 1,000,000 times, resulting in new varieties. Not considered GMOs PNAS report on review of current evidence, 2017: "The committee also examined epidemiological data on incidence of cancers and other human-health problems over time and found no substantiated evidence that foods from GE crops were less safe than foods from non-GE crops." 15 The Earth BioGenome Project: An Ambitious Goal to Sequence All Eukaryotes “The Earth BioGenome Project has proposed that the genomes of all extant, named eukaryotes—about 2 million species—should be sequenced to high quality to produce a digital library of life on Earth, beginning with strategic phylogenetic, ecological, and high-impact priorities.” “ We envisage that a genomic tree of life will foster understanding of the ongoing processes of speciation, adaptation, and organismal dependencies within entire ecosystems. These explorations will resolve long-standing problems in phylogenetics, evolution, ecology, conservation, agriculture, bioindustry, and medicine.” https://www.pnas.org/doi/10.1073/pnas.2115636118 16 Earth Biogenome Project https://www.earthbiogenome.org Sequence all known eukaryotic species Projected to cost $4.7 Billion 17 Metagenomics The collection of genomics in a coherent environmental sample Fairly recent development Examples: 1 ml of ocean water: 100-200 species 1 Gram of soil: 4000 Human gut: 500 Note: human microbiome includes all tissues, not only the gut 18 Applications of Metagenomics Human health gut biome has been tied to health antibiotics 30 days before chemo is tied to worse outcomes Agriculture gut biomes of animals In colony collapse disorder (CCD), honey bee colonies inexplicably lose their workers Metagenomics identified “Israeli acute paralysis virus of bees” as being strongly correlated with CCD Environmental remediation Anthropology Biotech 19 Gene terminology: Orthologues Paralogues: genes that have diverged from a common ancestor Orthologues: genes that perform the same function in different species 20 Pseudogenes Typically, non-functional genes Appear to be like existing gene sequences Likely to have arisen through DNA duplication (intron/exon structure maintained) Retro-transposition (RNA copied back into DNA – thus only exons, aka processed pseudogenes) 21 22 Source: Wikipedia 23 How Many Pseudogenes? Pseudogene.org -- comprehensive database and comparison platform for pseudogene annotation Not the most functional site Approximately 10,668 processed pseudogenes Cheetham, S.W., Faulkner, G.J. & Dinger, M.E. Overcoming challenges and dogmas to understand the functions of pseudogenes. Nat Rev Genet 21, 191–201 (2020). https://doi.org/10.1038/s41576-019-0196-1 14,000 non-processed pseudogenes Sun M, Wang Y, Zheng C, Wei Y, Hou J, Zhang P, He W, Lv X, Ding Y, Liang H, Hon CC, Chen X, Xu H, Chen Y. Systematic functional interrogation of human pseudogenes using CRISPRi. Genome Biol. 2021 Aug 23;22(1):240. doi: 10.1186/s13059-021- 02464-2. PMID: 34425866; PMCID: PMC8381491. 24 PTEN: Phosphatase and Tensin Homolog (a phosphatase removes phosphates from a protein) 25 Processed Pseudogene 26 Gene Names Ambiguous, aliases or synonyms, and Hemoglobin Subunit Gamma 1 historical names Hemoglobin Subunit Gamma-1 Example: http://genecards.org Hemoglobin Gamma-1 Chain Hemoglobin Gamma-A Chain Hemoglobin, Gamma A Gamma-1-Globin Hb F Agamma Hemoglobin, Gamma, Regulator Of Gamma A Hemoglobin A-Gamma Globin Gamma Globin PRO2979 HBG-T2 HSGGL1 HBGA HBGR HBG1 27 28 Gene Names Often named historically, making the name misleading: MAK: Male Germ Cell Associated Kinase Found to have a retina-specific exon, giving it a unique transcript seen only in retina 29 Globin Gene Clusters Chromosome 16: 151,641 - 182,080 Book says Chromosome 11: 5,216,332 - 5,517,130 these are pseudogenes 30 31 32 Note the strand orientation 33 34 35 36 HBBP1: Non-processed Pseudogene 37 38 Human genome 3.2 * 109 nucleotides (haploid) Chromosome sizes are 49 Mbp to 279 Mbp X 163 Mbp Y is 52 Mbp Repeated sequences: 50% !!! 39 Wikipedia 40 Cell senescence can arise as the result normal shortening of telomeric DNA. Senescence: cells irreversibly withdraw from the cell cycle and fail to respond to proliferation-inducing stimuli 41 42 43 44 45 Punchline 4813 genes – no idea what they do Thousands of transcripts (alternatively spliced) LncRNAs: Long-non-coding RNAs (length > 200 nucleotides) MicroRNAs: ~22 nucleotides in length whose function is RNA silencing 46 SNPs Single Nucleotide Polymorphisms Compare any 2 un-related individuals, they will be different at approximately 0.1% of sites (1 in 1,000). 3*109 * 0.001 = 3*107 = 30,000,000 differences 47 48 Browsers -- in "PanoramaOfLife-Intro" 49 Another Privacy Example For police officers around the country, the genetic profiles that 20 million people have uploaded to consumer DNA sites represent a tantalizing resource that could be used to solve cases both new and cold. But for years, the vast majority of the data have been off limits to investigators. The two largest sites, Ancestry.com and 23andMe, have long pledged to keep their users’ genetic information private, and a smaller one, GEDmatch, severely restricted police access to its records this year. However, a Florida detective announced at a police convention that he had obtained a warrant to penetrate GEDmatch and search its full database of nearly one million users. Legal experts said that this appeared to be the first time a judge had approved such a warrant, and that the development could have profound implications for genetic privacy. 50 https://www.heritage.org/crime-and-justice/commentary/gedmatch-and-the-fourth-amendment-no-warrant-required 51 From the Article: Another more recent case has been solved using this method. On May 6, 2021, a Florida jury found Thomas Garner guilty of first- degree murder for the 1984 death of Navy recruit Pamela Cahanes. The police did not need a warrant to query the public consumer genetics website, as some privacy advocates and legal scholars have argued. This type of search, called long-range familial searching, does not implicate the Fourth Amendment’s prohibition against unreasonable searches and seizures requiring law enforcement to obtain a warrant, even under the most expansive reading of recent Supreme Court precedent. 52 End 53 Golden Rice: GMO'ed to contain beta- carotene, precursor to Vitamin A Global and Social Awareness 54