6.3.2 Comparing Genomes

• A genome contains all of the genes within an organism
• Advances in technology have allowed scientists to sequence the genes within an organism's genome
• Sequencing projects have read the genomes of a wide range of organisms from flatworms to humans
• Genome-wide comparisons can be made between individuals and between species

Sequencing DNA to determine protein sequences

• The genetic code can be used to predict the amino acid sequence within a protein
• Once scientists know the amino acid sequence they can predict how the new protein will fold into its tertiary structure
• This information can be used for a range of applications, such as in synthetic biology

Bioinformatics

• Bioinformatics is a field of biology that involves the storage, retrieval, and analysis of data from biological studies
• These studies may generate data on DNA sequences, RNA sequences, and protein sequences, as well as on the relationship between genotype and phenotype
• High-power computers are required to create databases
• The large databases contain information about an organism's gene sequences and amino acid/protein sequences
• Once a genome is sequenced, bioinformatics allows scientists to make comparisons with the genomes of other organisms using the many databases available
• This can help to find the degree of similarity between organisms which then gives an indication of how closely related the organisms are
• This can be useful for scientists looking for organisms that could be used in experiments as a model organism for humans
  • E.g. The nematode worm Caenorhabditis elegans is an animal that has been used as a model organism for studying the genetics of organ development, neurone development and cell death. It was the first multicellular organism to have its genome fully sequenced and as it has few cells (less than 1000), and is transparent, it has been a useful model organism

• Bioinformatics has contributed to the study of genetic variation, evolutionary relationships, genotype-phenotype relationships, and epidemiology (see below)

Bioinformatics allows for large amounts of sequence data to be instantly available to researchers across the globe

Genetic variation and evolutionary relationships

• The genetic variation within a species can be investigated
  • Many individuals of the same species have their genomes sequenced and compared
  • A species that has a high level of genetic variation will exhibit a large number of differences in base sequences between individuals

• The evolutionary relationships between species can be investigated by comparing the genomes of different species
  • Species with a small number of differences between their genomes are likely to share a more recent common ancestor than species with a large number of differences
  • The protein cytochrome c is involved in respiration, and so is found in a large number of species (including plants, animals, and unicellular organisms). For this reason it is especially useful for making comparisons between different species

Genotype-phenotype relationships

• Genome sequencing can aid the understanding of gene function and interaction
• Genotype-phenotype relationships are explored by "knocking out" different genes (stopping their expression) and observing the effect it has on the phenotype of an organism
  • When an organism's genome sequence is known, scientists can target specific base sequences to knock out

Epidemiology

• Epidemiologists study the spread of infectious disease within populations
• The genomes of pathogens can be sequenced and analysed to aid research and disease control
  • Highly infectious strains can be identified
    • E.g. the Delta variant of SARS-CoV-2 (a well-known coronavirus)

  • The ability of a pathogen to infect multiple species can be investigated
    • E.g. Ebola can infect primates as well as humans

  • The most appropriate control measures can be implemented based on the data provided
  • Potential antigens for use in vaccine production can be identified

Genome comparison in action: The Human Genome Project

• A genome project works by collecting DNA samples from many individuals of a species. These DNA samples are then sequenced and compared to create a reference genome
  • More than one individual is used to create the reference genome as one organism may have anomalies/mutations in its DNA sequence that are atypical of the species

• The Human Genome Project (HGP) began in 1990 as an international, collaborative research programme
• It was publicly funded so that there would be no commercial interests or influence
• DNA samples were taken from multiple people around the world, sequenced, and used to create a reference genome
• Laboratories around the globe were responsible for sequencing different sections of specific chromosomes
• It was decided that the data created from the project would be made publicly available
  • As a result, the data can be shared rapidly between researchers
  • The information discovered could also be used by any researcher and so maximised for human benefit

• By 2003 the human genome had been sequenced to 99.9% accuracy
• The finished genome was over 3 billion base pairs long but contained only about 25,000 genes, a surprisingly low number
• Work is currently underway to sequence the human proteome and the human epigenome

Applications of the Human Genome Project

• The information generated from the HGP has been used to tackle human health issues with the end goal of finding cures for diseases
• Scientists have noticed a correlation between changes in specific genes and the likelihood of developing certain inherited diseases
• For example, several genes within the human genome have been linked to increased risk of certain cancers
  • If an individuals BRCA1 and BRCA2 genes are mutated then they are substantially more likely to develop breast cancer

• There have also been specific genes linked to the development of Alzheimer's disease