Chapter 18.2-5 Eukaryotic Genomes

18.2 Gene expression• Cell differentiation - process that

specializes the form and function of each type of cell in multi-cellular organisms

*humans have over 200 different types of cells

* about 20% of genes are expressed in humans

*1.5% of DNA codes for proteins

- smaller fraction codes for rRNA and tRNA

– rest is noncoding, may also transcribe into RNA with unknown functions

Chromatin Structure• Chromatin – the DNA-protein complex found in

eukaryotes-many structrural changes occur during cell cycle-Interphase- diffuse mass in the nucleus-G2 – coils up and condenses-Mitosis – apparent chromosome structure or sister chromatids

Histones• Histones – proteins responsible for first level of DNA

packing in chromatin- most histones are similar in eukaryotes as well as prokaryotes-gives evolutionary significance to the role histones

play in organizing DNA in cells• Nucleosomes – basic unit of DNA packing

-consists of DNA wound around protein core and containing two molecules of 4 types of histones

-changes to the shapes and positions of nucleosome can allow RNA polymerases to move along DNA

Histone Modifications• Mounting evidence indicates

that chemical modifications to histones plays a direct role in regulation of gene transcription

• Histone acetylation – attaching an acetyl group (COCH3) will loosen the condensed chromatin and in turn initiate transcription and recruit factors for the machinery

• Deacetylation – most likely inhibits transcription

DNA Methylation

• Attachment of methyl groups (CH3) to tail of DNA is thought to be essential for long term inactivation of certain genes

*Genomic imprinting - patterns of methylation passes from parent to offspring keeping record of what occurred during development

-permanently regulates expression of either maternal or paternal allele of certain genes

Enhancers for Transcription

Regulation of Transcription

• Control elements – segments of noncoding DNA that serve as binding sites for proteins (transcription factors) in eukaryotes

• 2 categories of Transcription factors1. general factors – essential for all protein coding genes2. specific factors – high levels of transcription of

particular genes at appropriate time and place-will increase or decrease rate of gene

expressionEx: proximal – close to promotor distal (enhancers) – far from promotor

or even in intron

Critical Gene Expression

• Transcription is the most critical stage in controlling gene expression

- enhancers matching control elements to each specific gene can activate machinery

• mRNA degradation and translation can also be checkpoints

• Proteasomes- giant protein complex that recognizes ubiquitin tagged proteins and cuts into small peptides initiating the degradation process

Degradation by Proteasomes

18.3 Noncoding DNA

• Coding for proteins and RNA products is only a tiny portion of the genome

• Bulk of genomes is mostly noncoding or “junk DNA”*Must have important role to persist

for hundreds of generationsEx: human genome has 500 to 1500

more base pairs in DNA compared to bacteria, but only 5 to 15 times more genes

Noncoding mRNA• Its now believed that 75% of the genome is

transcribed at some of a given cell• mRNA may be non protein coding but still serve a

purpose in controlling gene expression2 examples:

1. Micro RNAs(miRNA) - bind to complementary RNA, degrades or blocks translation

2. Small interfering RNA(siRNA) - similar to miRNA, but can bind and turn off gene expression (like methylation)

18.4 Embryonic Development

Morphogenesis – the development of the form of an organism and its structures

- differential gene expression results from the genes being regulated differently in each cell type-materials placed in the egg by the mother determine the sequential program of

regulation

Gene Expression Control• Important source in determining the differentiated

fate comes the egg’s cytoplasmcytoplasmic determinants – maternal substances

in the egg that influence course of early development- combinations of cytoplasmic determinants regulate expression of cell’s genes

• Another source is the environment around the cell- induction – process where signals from

neighboring cells and binding of growth factors cause changes in target cells

Gene Expression Control

• Determination – point at which an embryonic cell is irreversibly committed to becoming a particular cell type

- differentiation a cell attains its determined fate- expression of tissue specific proteins determine the outcome of determination

- presence of mRNA in proteins marks fatePattern formation – process in which cytoplasmic determinants and induction signals contribute the spatial organization of tissues and organs

18.5 Cancer

• Growth factors, their receptors, and signal pathway molecules regulate genes that control cell growth and division

-any mutation to these genes in somatic cells can lead to cancer-cancer causing mutations can be

spontaneous or caused by environmental influences such as X-rays, chemical carcinogens, and certain viruses

Genes linked to Cancer

• Proto-oncogens- normal cellular genes that code for proteins to stimulate growth and division

• Oncogenes- cancer causing genes

How does the normal proto-oncogene become an oncogene?

Proto into oncogene• 3 mechanisms: (common link is abnormal stimulation

of cell cycle and path to malignancy)1. Movement of DNA within the genome2. amplification of proto-oncogene3. point mutation in control element

Tumor suppression

• Tumor suppressor genes – products found within the cell that inhibit cell division to prevent uncontrolled cell growth

-any mutation can reverse this activity and lead to onset of cancer

Interference with Signaling Pathways

P53 Gene

• P53 gene- “guardian angel of genome”-activated by DNA damage can prevent passing of mutations 3 ways:1. can function as an activator to signal genes to halt cell cycle and allow repair2. can directly turn on genes involved in DNA repair3. can cause apoptosis or cell death to genes that are irreparable

Multistep Progression

• Usually more than one somatic mutation is needed for a cell to become full fledged cancer

• Accumulations of mutations with throughout life means longer life increased likelihood of cancer

Steps:1. appearance of a polyp (benign)2. tumor grows and becomes malignant3. accumulations of mutations that converts

proto-oncogenes to oncogenes4. Knock out or mutation of tumor suppressor

genes

Multistep Progression

What percentage of cancers develop from viruses?

Is inheritance a link to predisposition of cancer?