Human Genome Complexity, Viruses & Genetic Variability

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

• 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

The Human Genome sequences

• 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

Noncoding RNAs

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

Repeated DNA Sequences

Exons (regions of genes codingfor protein, rRNA, or tRNA) (1.5%)

Alu elements (10%)

Simple sequenceDNA (3%)

Large-segmentduplications (5–6%)

UniquenoncodingDNA (15%)

Introns andregulatorysequences(24%)

RepetitiveDNA thatincludestransposableelementsand relatedsequences(44%)

RepetitiveDNA unrelated totransposableelements(about 15%)

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

Viruses

• To replicate they need to infect a living cell• Every living cells has one or more viruses that

can infect it, specifically.

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

Membranousenvelope

RNA

Proteincoat

Glycoprotein spike

Viral genomes are made of either DNA or RNA– Flu viruses are RNA– Genital warts virus (HPV) and Herpes virus are DNA

viruseshttp://www.cdc.gov/STD/HPV/STDFact-HPV.htm

HPVInfluenza

Emerging viruses threaten human health

Colo

rized

TEM

50,

000×

Colo

rized

TEM

370

,000×

Figure 10.20A, B

Ebola Virus (RNA) SARS Virus (RNA)

RNA

Capsomere

Capsomereof capsid

DNA

Glycoprotein18 250 nm 70–90 nm (diameter)

Glycoproteins80–200 nm (diameter) 80 225 nm

Membranousenvelope RNA

Capsid

HeadDNA

Tailsheath

Tailfiber

50 nm50 nm50 nm20 nm(a) Tobacco mosaic

virus(b) Adenoviruses (c) Influenza viruses (d) Bacteriophage T4

Naked EnvelopedComplex

Viral Shapes

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

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.

http://www.susanahalpine.com/anim/KubyHTML/HIV.htm

Envelope

Glycoprotein

Protein coat

RNA (two identical strands)

Reverse transcriptase

• About 8% of our genome is derived from RNA retroviruses- This is evidence of past infection- Sequences tend to increase over time

Viral DNA

Figure 11.11

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

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