genomics and bioinformatics

whats a genome

• all nuclear DNA and genetic material of plastids (mitochondrial, chloroplasts)

how many genes do homo sapiens have

• 23K genes

what is the C value paradox

• genome size does not increase with perceived complexity of organisms

• genome size does not mean more genes

why do some simple organisms have huge genomes

• lots of DNA is non coding

• not all DNA = genes

what is the genome architecture

• only tiny part codes for proteins - mostly non coding

• 1.5% - exons

• repetitive DNA (‘junk’ DNA) makes up huge part

whats included in non coding DNA

• Introns

• regulatory sequences

• repetitive DNA - tandem repeats and transposable elements

• non coding RNA genes - rRNA, tRNA, miRNA (gene silencing)

what is repetitive DNA

tandem repeats:

• repeated next to each other

• microsatellites and minisatellites

• originated by strand slippage during DNA replication

transposable elements:

• DNA that can move around the genome

• discovered by barbara McClintock - identified changes in colour of corn kernels - only made sense if some genetic elements moved

• DNA transposons - ‘cut and paste’

• RNA transposons - ‘copy and paste’

• can move genes, change gene expression, cause mutations and affect recombination

• Alu elements - most abundant gene in human genome

what is epigenetics

• heritable changes of genetic information not caused by changes in the DNA sequence

what are the mechanisms of epigenetics

• histone modification

• DNA methylation - addition of CH3 makes DNA inaccessible

• genomic imprinting - only one copy of an allele is expressed - one copy switched off

difference between 1st, 2nd and 3rd generation sequencing

1st:

• shotgun (sanger) sequencing

2nd:

• example = illumina

• do NOT need priori genetic info (primers for PCR)

3rd:

• example - nanopore

• do NOT need priori genetic info

• focus on a single molecule sequencing

• no need for shotgun sequencing

what are orthologs

• same gene in different species

• came from common ancestor

what are paralogues

• genes duplicated within one species

• can evolve new functions

what is a complication with evolutionary trees

• horizontal gene transfer

• genes move between species

• can confuse evolutionary trees

what are homologous traits

• same origin - shared ancestor

• e.g arm bones in humans, bats, whales

what are analogous traits

• same function but different origin

• due to convergent evolution

• e.g wings in birds vs insects

what is the C value paradox

• idea that some simple organisms can have more DNA than more complex ones

• genome size does not equal complexity

what are the types of coding and non coding DNA

Coding:

• Exons - make proteins

Non - Coding:

• introns

• regulatory DNA

• RNA genes (make RNA not proteins)

most DNA does not directly make proteins

what are some important functions of Non-coding DNA

• rRNA - helps build ribosomes

• tRNA - brings amino acids

• miRNA - controls gene activity

• so non coding DNA Is important in control and regulation

What are the two types of repetitive DNA

1. Tandem repeats - repeated next to each other e.g microsatellites (used in DNA fingerprinting)

2. transposable elements - DNA that can move around the genome

What are transposons

• ‘jumping genes’

• discovered by barbara mcClintock

• two types

• DNA transposons - cut and paste

• RNA transposons - copy and paste - make copies of themselves

• they can disrupt genes, change gene activity and help evolution

what are Alu elements

• very common repetitive DNA

• about 10% of the human genome

• may help regulate genes

why are some genomes really large

• often have lots of repetitive DNA

• many transposons

• polyploidy (extra copies of chromosomes)

what is the definition of epigenetics

• heritable changes of genetic information not caused by changes in the DNA sequence

• dna stays the same but gene can be turned on and off

• epigenetics explains how cells become different, how environment affects genes and how organisms adapt

how does epigenetics work

1. histone modification - chemical changes to histones - loosen DNA - gene on or tighten DNA - gene off

2. DNA methylation - adding a CH3 group to DNA - makes DNA hard to access, turns genes off

3. RNA interference - small RNA’s can block gene expression and stop proteins from being made

what is genomic imprinting

• only one parents gene is active

• in females one X chromosome is turned off

what are the types of genome sequencing

1. first generation

• slow and expensive

• used to sequence human genome

2. second generation

• faster and cheaper

• no prior DNA info needed

• can sequence a human genome in under a week

3. third generation

• reads single DNA molecules

• even faster and more advanced

what is BLAST

• basic local alignment search tool

• algorithm for comparing primary biological sequence information

• google for genes

• this allows us to use a single sequence to find one or more sequences

• used to compare a DNA or protein sequence to a database

• find similar sequences

what are the BLAST steps

1. input your sequence

2. BLAST splits the sequence into smaller chunks

3. search database - it looks for matches in a big database of sequences

4. find intial matches

5. extend matches

6. score matches

7. calculate significance - E value - shows how likely match is by chance - E value of 0 means highest probability of having found an exact match