Eukaryotic Genomes

The Organization and Control of Eukaryotic Genomes

Gene Expression In multicellular organisms, the first

place gene expression is controlled is through cell differentiation After the zygote forms and cells are

forming through mitosis, cells are “programmed” to become specific cell types

Depending on the cell type, certain “sets” of genes will be expressed

Gene expression Since each cell has all the DNA of the

organisms’ genome, the cell type is not controlled by the presence of “certain” genes

Instead, only certain genes are “active” (only about 17% of a cells genes) This process of differential gene

expression determines cell type and function

NOTE: Only about 3% of the DNA in your genome actually codes for proteins

Overview of the different ways that eukaryotic genes can be expressed in cells

Chromatin Structure: Tightly bound DNA

less accessible for transcription

DNA methylation: methyl groups added to DNA; tightly packed; transcription

Histone acetylation: acetyl groups added to histones; loosened; transcription

Acetylation of histone The protein side chains of the histone

molecule normally have charges associated with them REMINDER: Protein structure – the side

chains allow the amino acids to bind to each other and create a tertiary protein structure

When you acetylate the histone tails, you BLOCK these charges and allow the chromatin to unravel.

DNA Methylation DNA methylation also seems to be

responsible for inactivating certain genes (blocks them from transcription) Again, this aids in cell differentiation Methylation is what is responsible for

genomic imprintingFrom previous unit (where gene

expression is determined by the parent the allele was inherited from)

Epigenetic Inheritance Modifications on chromatin can be passed

on to future generations Unlike DNA mutations, these changes to

chromatin can be reversed (de-methylation of DNA)

This can affect the expression of different genes (do you have transcriptional access?)

Explains differences between identical twins

Transcription Initiation:

Control elements: segments of noncoding DNA that can bind transcription factors (proteins that aid RNA polymerase in transcription)

Enhances gene expression

Activator vs. RepressorThere are distant control elements

(enhancers) on the DNA strand that can affect transcriptionActivators is a protein complex

that binds to the enhancer help initiate transcription

Repressors are protein complexes that inhibit transcription

EnhancerEnhancer regions bound to promoterpromoter region by activatorsactivators

Regulation of mRNA:• One way to regulate mRNA

is by alternate splicing• This allows the splicing of

different exons and introns to alter protein expression

• micro RNAs (miRNAs) micro RNAs (miRNAs) and small interfering small interfering RNAs (siRNAs) RNAs (siRNAs) can bind to mRNA and degrade it or block translation

RNA inhibitionmicroRNAs (miRNAs)Single stranded RNA molecules that bind to mRNAThese allow the mRNA strand to be degraded or blocks translation

Small interfering RNAs (siRNAs)

Similar to miRNAsSince these usually destroy the mRNA strand, it is believed to have developed to fight viruses

Translation Controls Regulatory proteins can alter translation:

Certain mRNA sequences can be blocked and prevent attachment to the ribosome

Enzymes can add to the poly-A tail of mRNA to aid translation of the mRNA

Global regulation: Either activate or inactivate protein

factors that affect the initiation of translation

Protein modification Regulatory proteins can affect the

modification of proteins created after translation: Can affect phosphorylation (alter shape) Alter protein markers to alter the destination

of protein Regulate the life-span of proteins

Label proteins with a molecule called ubiquitin

Proteins called proteasomes recognize the ubiquitin and degrade the protein

Genomic DNA and evolution

Mutation The basis for change at the level of DNA

is mutation Earliest life probably had a limited

number of genes (simple organisms) Mutations allowed for genetic sequences

not only to change, but to grow and incorporate additional genetic information into the genome

Chromosome duplication Because of an accident in meiosis

(nondisjunction), the number of chromosomes can be altered in a cell (remember trisomy)

These extra sets of genes can persist and acquire mutations (eventually new species)

Therefore, it is possible to acquire new “traits” that can be passed on to offspring If the trait is lethal, the individuals that have

the gene are carriers Possible method that genetic diseases arose

Crossing over Crossing over allows for a tremendous

amount of variability Errors in crossing over can cause deletions

or duplications of genetic material If you have duplication errors, you can

create a lot of genes with similar functions (create similar proteins)

EXAMPLE: Similarities in the globin proteins (a family of proteins with varied functions)

Transposable elements Sometimes there are segments of DNA

that can “cross-over” when the chromosomes are not aligned or cross-over to non-sister chromatids

These “jumping genes” introduce even more chances for mutation

There are still quite a few transposable elements remaining in the eukaryotic genome . . . possible future mutations

Exon duplication/shuffling Not all DNA codes for proteins (introns

vs. exons) Some exons could be duplicated or

deleted from chromosomes Gives the freedom to rearrange exon

sequence and alter amino acid sequence This shuffling of amino acids can create

variations of the protein with similar (but new) functions