Human Genome Complexity, Viruses & Genetic Variability

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1 Human Genome Complexity, Viruses & Genetic Variability (Learning Objectives) Learn the types of DNA sequences present in the Human Genome other than genes coding for functional proteins. Review what you previously learned about: DNA sequences: non-coding promoters and introns Genes that code for functional RNA such as t-rna and r-rna Pseudogenes, transposons, centromeres, and telomoeres Compare and contrast viruses with living cells: structure and functional properties. Learn the biochemical nature of viral components: genome (DNA or RNA), capsid and envelope. Which are present in all or in some viruses? Learn the parasitic nature of viruses and explain: host-cell specificity: relate to common human diseases the steps of the life cycle of animal viruses and association with susceptibility to infection. Role of human genetic variability in susceptibility to viral infections Learn the life cycle of a retrovirus such as HIV and how its genome inserts itself into the DNA of humans. Explain the role of ancient and current retroviruses shaping the human genome and in adding to the genetic variability crucial for evolution of humans and behavior. Explain the role of ancient and current viral infections as selective pressure affecting human genetic variability

2 The Human Genome sequences Most of our genome does not code for proteins - Only 1.5% of human DNA encodes protein - Rest of genome includes: - Promoters and other control sequences - Introns - DNA Sequences for non-coding RNAs - Repeated DNA sequences - DNA of ancient viruses

3 Noncoding RNAs Nearly all of the human genome can be transcribed as non-coding RNAs (ncrnas), including rrnas and trnas There are hundreds of thousands of other ncrnas - transcribed from pseudogenes - not translated into protein

4 Repeated DNA Sequences A. Transposons are the most abundant type of repeat - Sequences that jump about the genome B. Other classes of repeats include those that comprise telomeres, centromeres, and rrna gene clusters

5 Exons (regions of genes coding for protein, rrna, or trna) (1.5%) Repetitive DNA that includes transposable elements and related sequences (44%) Introns and regulatory sequences (24%) Alu elements (10%) Repetitive DNA unrelated to transposable elements (about 15%) Unique noncoding DNA (15%) Simple sequence DNA (3%) Large-segment duplications (5 6%)

6 Viruses Viruses are genes packaged in protein Biological entities Have no cytoplasm Cannot self-replicate Cannot metabolize Genetic material either DNA or RNA never both

7 Viruses To replicate they need to infect a living cell Every living cells has one or more viruses that can infect it, specifically.

8 Basis of Host-Range of Viruses Lock-and-key fit between virus surface and cellular receptors on host cell Narrow host-range with tissue specificity Viruses infect only specific types of cells in one host cold viruses: upper respiratory tract cells. HIV, AIDS virus: a certain white blood cell. Some have a broad host-range infecting multiple species rabies

9 Viral genomes are made of either DNA or RNA Flu viruses are RNA Genital warts virus (HPV) and Herpes virus are DNA viruses Membranous envelope RN A Protein coat Glycoprotein spike Influenza HPV

10 Emerging viruses threaten human health Colorized TEM 50,000 Colorized TEM 370,000 Figure 10.20A, B Ebola Virus (RNA) SARS Virus (RNA)

11 Naked Viral Shapes Enveloped Complex RNA Capsomere DNA Membranous envelope Capsomere of capsid Glycoprotein Glycoproteins nm nm (diameter) RNA Capsid Head nm (diameter) nm DNA Tail sheath Tail fiber 20 nm (a) Tobacco mosaic virus 50 nm 50 nm 50 nm (b) Adenoviruses (c) Influenza viruses (d) Bacteriophage T4

12 Animal Virus Life Cycle Attachment Entry Uncoating of virion separate protein from NA Replication of nucleic acid and synthesis of viral proteins Maturation of virions (assembly of NA and proteins) Release: cell lysis or budding Role for human genetic variability in completion of viral life cycle

13 Retroviruses can inert viral genome in the human DNA Some jump from one species to another. Example, HIV the AIDS virus Retro- comes from ability to reverse transcribe making DNA using RNA template Inside a cell, HIV integrates the copy of DNA of its genome into the host genome. Envelope Glycoprotein Protein coat RNA (two identical strands) Reverse transcriptase

14 Viral DNA About 8% of our genome is derived from RNA retroviruses - This is evidence of past infection - Sequences tend to increase over time Figure 11.11

15 Role for Virus in shaping the Human Genome Past retroviral infection in a primate ancestor Insertional mutagenesis New proteins or protein domains for host that maybe beneficial and influence behavior Adding to the Genetic Variability of human populations

16 Role of Current Viral infections as selective pressure Influencing the genetic variability in human populations Viral genetic variants Host factors: susceptibility genes the host immune response molecular interactions between viral proteins and host proteins throughout viral life cycle

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