lecture 1: genes & genomes Flashcards
what is a genome?
- A genome is an organism’s complete set of DNA.
- Each genome contains all the information needed to build & maintain that organism
genome size
- morphologically similar organisms have very different genome sizes
- genome size doesn’t correlate with organismal complexity or size of the organism
how are genomes organised?
- organised into chromosomes
- BUT chromosome number doesn’t necessarily correspond to genome size
what are the non-coding elements that make up genomes?
- gene control regions
- introns
- regions coding for functional RNA
- centromeres
- telomeres
- origins of replication
what are the coding regions of a genome?
- genes
- abot 98% of the genome is non-coding
definiton of genes
a basic, physical unit of heredit; a linear sequence of nucleotides along a segment of DNA that provides the coded instructions for synthesis of RNA which when translated into protein, leads to expression of hereditary character.
what is the c value?
the total number of base pairs per haploid genome
what is the c value paradox?
related to the non-linear relationship between genome size, number of protein synthesised and organismal complexity
what is the structure of a typical human gene?
- ATG is the translation start site
- STOP is translation stop site
- UTRs (untranslated regions) are transcribed but not translated
- coding regions (exons) are separated by introns; transcribed but not translated
what are UTRs?
an untranslated region on either side of a coding sequence on a strand of mRNA
- variable from protein to protein
the size of UTRs
wide variation (from 7 to several thousand)
what do these UTRs contain?
- elements that control the translation, degradation and localisaiton of the mRNA
- e.g:
stem loop structures, upstream initiation codons & open reading frames, internal ribosome entry sites & various cis-acting elements that are bound by RNA binding proteins
introns and exons
- number of introns per gene vary (average is 7-8)
- sizes of them vary
- some organisms have no introns
- recognised by specific sequences at 5’ and 3’ junctions that allows them to be recognised and targeted for removal by splicing
what is splicing?
- occurs at the end of the transcription process as part of the pre-mRNA processing
- coding regions of mRNA (exons) are kept and non-coding (introns) are removed
what is alternative splicing?
a cellular process in which exons from the same gene are joined in different combinations leading to different but related mRNA transcripts
RNA editing
- discreet changes made after the RNA has been transcribed usually at single nucleotide level.
- can be insertion, deletion or deamination
intron retention
occurs where a complete and unspliced intron remains in mature DNA
-VERY RARE
where was RNA editing first found?
in trypanosomes but also in humans
- e.g. the apolipoprotein B gene
genes in lower eukaryotes
often (but not always) only have 1 copy of a gene
multigene families
- quite often in mammals, several copies of a gene in a genome
on what terms of multigene families do they vary?
- the number of family members (2-hundreds)
- how closely related the copies are (very close- distantly related)
- genomic locations (different regions of the genome, located close to each other sometimes in clusters, can be more than 1 cluster in the genome)
pseudogenes
- as well as active copies, gene genomes can also contain pseudogenes
- contain coding information but are not expressed to the lack of appropiate controlling elements
chromosomal instability (CIN)
gains or losses of whole chromosomes as well as inversions, deletions, duplications & translocations of large chromosomal segments
nucleotide level instability
mutations of single or small goups of nucleotides; not visible morphologically; trinucleotide repeate diseases.
what are SNPs
- single nucleotide polymorphism
- natural variation
- can be used as signposts for disease susceptibility & drug reaction
what is an operon?
a unit made up of linked genes which is thought to regulate other genes responsible for protein synthesis
bacteria & operons
bacteria contain the ‘lac operon’ which represents the most extreme type of clustering
do eukaryotes have operons?
with the exception of slime molds, eukaryotic operons are very RARE but they still have co-translation of genes by other mechanisms many of which can operate over long distances and on different chromosomes.
gene expression
cell identity is largely determined by gene expression profile of the cell.
Therefore, robust mechanisms must be in place to ensure that this is set up and maintained accurately.
process of gene expression
modification of DNA > Transcription > Post-transcription > Translation > Post-translation
mitochondrial genes
- mitochondrial have their own genomes
- codes for 35 proteins related to mitochondrial functions
- genome is circular
- multiple genes inside a single mitochondrion
- no chromatin structure
- only 3% is non-coding
- inheritance is maternal only
-genes are transcribes more like bacterial genes in poly-cistronic manner - plays a role in aging
chloroplast genome
- have their own genomes
- codes for 100 proteins also mainly for processes related to chloroplast function
- genome is circular
- multiple genes (15-20) inside single chloroplast
- no chromatin structure
- genes are transcribed in operons like bacterial genes
- usually chloroplast genome contains two inverted repeates that mirror images of one another in terms of gene complement
- 43% non coding
genome knowlege and diagnosis:
- simple disease (only 1 locus involved)
- complex disease (byproduct of multiple loci)
- different mutations in any of these genes
genome knowledge and treatment:
- is drug used appropriate for cause of that patients problems (different causes of condition/polymorphisms)
- is dosage used appropriate for individual
techniques for genome analysis
- DNA sequencing: hi throughput next gen sequencing
- linkage studies
- analysis of polymorphisms : SNP analysis to give HAPMAP
- genetic studies: marker analysis/ co-segregation traits
- microarrays
- RNAseq
- proteomics changes in protein/modifications
