Unit 1 1.8- Genomic sequencing Higher Biology Unit 1 1.8- Genomic sequencing

Genomics Genomics is the study of the genome It involves determining the sequence of nucleotide bases all the way along an organism’s DNA This allows scientists to relate the genetic information about genes to their functions

Genomic Sequencing To sequence a genome it needs cut into smaller pieces using an enzyme called restriction endonuclease Restriction endonuclease recognises a specific short sequence of DNA nucleotides called a restriction strand The DNA strand will be cut at this restriction site all along the strand

Genome shotgun One copy of the genome will be cut up using a restriction endonuclease Another copy of the genome will be cut up using a different restriction endonuclease Each genome is cut at different points as the enzymes recognise different restriction sites

Each DNA fragment is then sequenced to determine the order of bases on it This information is entered into a computer which works out the sequence of fragments The computer will recognise where there is an overlap in the sequence of bases and determine that the end of one fragment is the start of another The computer will work this out for all fragments and will compile a complete genome This allows the sequencing of individual genes as well as entire genomes

Importance The nucleotide sequence of the genome of different species has been determined In 2003 the DNA sequence of the human genome was successfully sequenced Other organisms whose genomes have been sequenced include: viruses, bacteria, pest species and model organisms used for research

Comparative genomics Comparative genomics compares the sequenced genomes of member of different species, members of the same species and allows comparison between cancerous cells and healthy cells in an individual. Comparing genomes can determine the sequences of DNA that cause illness

Differences in genome One way that the genome of 2 individuals of the same species can be found to differ is a single base pair This is knows as a single nucleotide polymorphism (SNP) By mapping and cataloguing SNPS scientists believe they will be able to identify and understand how genes affect disease

Genomic similarities Sequencing of the genome also shows important similarities Different genomes may show a high level of conservation, where similar or the same DNA sequences are present in the genome. Among the most highly conserved genetic sequences are those that code for the active sites of essential enzymes

Highly conserved DNA sequences can be used to compare the genomes of two organisms to find out closely or distantly related they are The greater the number of conserved DNA sequences in common the more closely related the organisms are

Phylogenetics Phylogenetics is the study of evolutionary relatedness among different groups of organisms Sequences of events involved in the evolution of a species (known as phylogenies) can be worked out using comparisons of genomes Diagrams can then be constructed to show evolutionary relationships (phylogenetic tree)

This representation of evolution is wrong This representation of evolution is wrong. Monkeys, apes and humans evolved from a common ancestor as populations split off and adapted to their environment.

Common ancestors This is the correct representation of evolution. Each “branch” splitting off shows a common ancestor that a group of organisms evolved from. In the above example humans share a common ancestor with gibbons, orang-utans, gorillas and chimpanzees. The distance between organisms represents how closely related they are. For example humans are more closely related to chimpanzees than they are to gibbons.

Divergence The genome of groups of closely related organisms will change over time due to mutations If this results in 2 or more distinct groups that become increasingly different from each other we call this divergence Looking at molecular information to establish evolutionary relationships is called molecular phylogenetics This is a much more conclusive way of assessing relatedness than comparing physical structures

Molecular clocks By comparing the equivalent genetic sequences of 2 organisms the length of time since the 2 groups diverged can be measured A molecule of nucleic acid (or protein coded for by it) can therefore be regarded as a molecular clock The number of molecular difference can then be compared to fossil records This can be used to try to date the origin of groups of living things and the sequence in which they evolved

The graph shown is produced using molecular clock information. A limitation of molecular clock use is that it works on the assumption that mutations occur at a relatively constant rate. This is less reliable for use in dating the origins of distantly related groups.

Domains Sequences of DNA and RNA have been used to trace the evolutionary lineage of all living things This has been largely based on ribosomal RNA (rRNA) from different organisms The genes that code for rRNA are ancient, have suffered little or no horizontal gene transfer and are present in all living things, making them useful as molecular clocks Using this information we can divide living things into 3 domains: Bacteria (prokaryotes) Achaea (prokaryotes that inhabit extreme environments) Eukaryotes (fungi, plants and animals)

3 domains