ka8: genomic sequencing

•  In genomic sequencing the sequence of nucleotide bases can be determined for individual genes and entire genomes.

  • Computer programs can be used to identify base sequences by looking for sequences similar to known genes.
• Comparison of genomes from different species.

  • To compare sequence data, computer and statistical analyses (bioinformatics) are required
• Comparison of genomes reveals that many genes are highly conserved across different organisms.

  • Many genomes have been sequenced, particularly of disease-causing organisms, pest species and species that are important model organisms for research.
• Use of sequence data and fossil evidence to determine the main sequence of events in evolution of life: cells, last universal ancestor, prokaryotes, photosynthetic organisms, eukaryotes, multicellularity, animals, vertebrates, land plants.
• • Molecular clocks are used to show when species diverged during evolution. They assume a constant mutation rate and show differences in DNA sequences or amino acid sequences. Therefore, differences in sequence data between species indicate the time of divergence from a common ancestor.
• An individual’s genome can be analysed to predict the likelihood of developing certain diseases.
• Pharmacogenetics is the use of genome information in the choice of drugs
• • An individual’s personal genome sequence can be used to select the most effective drugs and dosage to treat their disease (personalised medicine).
• Genomics is the study of genomes.  In order to study genomics you must first determine the entire DNA sequence of the organism.  The sequence of nucleotide bases can be determined for individual genes and entire genomes.  To compare sequence data, computers and statistical analyses are required. This fusion between molecular biology, statistical analysis and computer technology is called bioinformatics.
• This involves comparing the genomes of:

  • Members of different species.
  • Members of the same species.
  • Cancerous versus normal cells
• This process can identify similarities or differences in the genomes.  These could give clues to causes of disease etc.  As well as sequencing the human genome, scientists have determined the genome sequence of a range of other organisms:

  • Disease causing (pathogenic) bacteria or viruses.
  • Pest species e.g. mosquitoes.
  • Model organisms – so called because they possess genes equivalent to human genes and can be easily studied in the lab.
• Comparison of many genomes has revealed that DNA sequences of many genes are highly conserved (similar) across different species.  For example, genes coding for proteins involved in aerobic respiration or for key enzymes.
• Phylogenetics is the use of sequence data to study the evolutionary relatedness among groups of organisms.  Closely related species are found to have genomes that are very similar in the sequence of their nucleotide bases.
• Over time a group of closely related living things will accumulate mutations, e.g. nucleotide substitutions, which gradually alter the genome.
• If the group gives rise to two groups that become more and more different from one another and eventually diverge, then changes accumulate in each group’s genome that are distinct from those occurring in the other group’s genome.
• this is known as sequence divergence.  It can be used to estimate the time since lineages diverged
• sequence divergence

  
• The number of these differences per unit length of DNA between two genomes gives a measure of how related two genomes are (evolutionary distance).
• Mutations accumulate at a steady rate over time. Therefore the number of nucleotide substitutions that a genome accumulates is regarded as being proportional to time.
• By comparing this data with fossil records, the molecular clock gives information about how long ago the most recent common ancestor of the species existed and the sequence in which the species evolved
• molecular clocks

  
• The use of these techniques has allowed for many discoveries.  The comparison of sequence data and fossil evidence have allowed the main sequence of events in evolution of life to be placed on a timeline (see diagram below).

  
• Analysis of ribosomal RNA (rRNA) nucleotide sequences from many organisms have been studied because they are shared by all living things.
• Comparing the sequences has given clues to the evolution of all living things and demonstrated that all life belongs to one of three domains:

  • Bacteria – traditional prokaryotes.
  • Archea – mostly prokaryotes that inhibit extreme environments, e.g. hot springs and salt lakes.
  • Eukaryotes – fungi, plants and animals.
• Sequencing of genomes has shown the archaen genes involved in DNA replication, transcription and translation to resemble much more closely to eukaryotes than those of bacteria.  The deep evolutionary divisions that separate bacteria and archaea were not obvious from their phenotypes and only came to light following comparison of their rRNA.
• Personal genomics involves sequencing an individual’s genome and analysing it using bioinformatics tools.  Analysis of an individual’s genome may lead to personalised medicine through knowledge of the genetic component of risk of disease and likelihood of success of a particular treatment.
• • Predictive medicine

  Once you have your DNA sequence you could look for disease causing mutations.  Mutations that increase your likelihood of developing a condition e.g. BRAC1 and 2 genes and breast cancer.
• • Pharmacogenetics

  The use of genome information in the choice of drug. Knowing the genome sequence could be used to predict which medicines, and which dosages, will be most effective in one person compared to another.
• Many different types of variation in genomes are found to occur among members of a human population. These differences are largely the result of mutations and rearrangements of parts of the sequences of bases. Genetic variation can result in a genetic disorder or disease.