DNA Databases and Genomic Data

The Human Genome Project (completed 2003) sequenced all 3.2 billion base pairs of human DNA. Today, sequencing a human genome takes less than a day and costs under $1000. This flood of data requires powerful computational tools to store, search, and analyse. Bioinformatics is the interdisciplinary field that develops these methods and software.

Major Biological Databases

GenBank (NCBI)

Open-access collection of all publicly available DNA sequences. Over 200 million sequences.

UniProt

Comprehensive protein sequence and function database. Links sequences to structure and function.

PDB

Protein Data Bank: 3D structures of proteins and nucleic acids determined by X-ray or cryo-EM.

Data Formats

FASTA format: A text-based format for representing nucleotide or protein sequences. Each entry begins with a > symbol followed by a description line, then the sequence.

Example: >Human_insulin | MALWMRLLPL LALLALWGPD PAAAFVNQHL CGSHLVEALY...

Sequence Alignment

Sequence alignment is the process of arranging DNA, RNA, or protein sequences to identify regions of similarity. Similarities may indicate functional, structural, or evolutionary relationships between sequences. The most widely used tool is BLAST (Basic Local Alignment Search Tool).

Pairwise Sequence Alignment Example

Sequence 1: A T G C C T G A T T A C G

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Sequence 2: A T G C C T A A T T A C G

Vertical bars indicate matching bases. Highlighted regions show conserved segments that may be functionally important.

Global Alignment

Aligns sequences across their entire length. Best for sequences of similar length and high overall similarity (e.g., comparing homologous genes from closely related species).

Local Alignment (BLAST)

Finds regions of local similarity within longer sequences. Ideal for finding conserved domains or when sequences differ significantly in length. BLAST searches billions of sequences in seconds.

Genomics Applications

Bioinformatics drives advances across many fields, from personalised medicine to conservation biology. By comparing genomes, scientists can identify disease-causing mutations, develop targeted drugs, trace evolutionary relationships, and even solve crimes.

Applications of Bioinformatics

Personalised Medicine

Analyse a patient's genome to select the most effective drug and dosage (pharmacogenomics)

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Forensic Identification

DNA profiling compares short tandem repeat (STR) patterns to identify individuals

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Agricultural Genomics

Identify genes for drought resistance, disease resistance, and improved yield in crops

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Phylogenetics

Build evolutionary trees by comparing DNA sequences across species

COVID-19 and Bioinformatics

The rapid global response to SARS-CoV-2 relied heavily on bioinformatics. The virus genome was sequenced within weeks, enabling mRNA vaccine design, variant tracking through genomic surveillance, and contact tracing -- all powered by computational analysis of genetic data.

Key Vocabulary

Bioinformatics

An interdisciplinary field combining biology, computer science, and statistics to analyse and interpret biological data, particularly large-scale genomic datasets.

Sequence Alignment

The arrangement of two or more biological sequences to identify regions of similarity that may indicate functional, structural, or evolutionary relationships.

BLAST

Basic Local Alignment Search Tool -- an algorithm that rapidly compares a query sequence against a database to find regions of local similarity and statistical significance.

Genomics

The study of an organism's complete set of DNA (genome), including gene interactions, mapping, and how genetic information relates to biological function and disease.

Worked Examples

1

Two DNA sequences are aligned: ATGCCTGA and ATGCATGA. Calculate the percentage sequence identity.

Step 1: Align the sequences and count matching positions:

ATGCCTGA vs ATGCATGA → matches at positions 1,2,3,4,6,7,8 (7 out of 8)

Step 2: Position 5 differs: C vs A

Answer: Sequence identity = (7/8) × 100 = 87.5%. This high similarity suggests the sequences are likely homologous.

2

Explain how BLAST could be used to identify a newly discovered gene's function.

Step 1: Enter the unknown gene's DNA (or protein) sequence as a query in BLAST.

Step 2: BLAST compares the query against millions of known sequences in databases like GenBank.

Step 3: Results show sequences with statistically significant similarity, ranked by E-value (lower = more significant).

Answer: If the unknown gene closely matches a gene of known function in another organism, we can infer (by homology) that the new gene likely has a similar function. This is the principle of functional annotation by homology.

3

A phylogenetic analysis of a gene shows that human and chimpanzee sequences differ by 1.2%, while human and mouse sequences differ by 15%. What does this tell us about evolutionary relationships?

Step 1: Greater sequence similarity indicates more recent common ancestry (molecular clock principle).

Step 2: Human-chimpanzee: 1.2% difference = very closely related, recent divergence (~6 million years ago).

Answer: Human-mouse: 15% difference = more distantly related, earlier divergence (~80 million years ago). The data confirms that humans share a much more recent common ancestor with chimpanzees than with mice, consistent with the established phylogenetic tree.

Knowledge Check

Select the correct answer for each question. Click "Check Answer" to see if you are right.

Question 1

BLAST is primarily used to:

Sequence DNA in a laboratory Compare a query sequence against a database to find similar sequences Edit genes using CRISPR technology Visualise protein structures in 3D

Question 2

Two genes from different species show 95% sequence identity. This most likely indicates:

The genes evolved independently by chance The species are unrelated The genes are homologous and share a common ancestor One gene was artificially inserted into the other species

Question 3

The Human Genome Project was significant because it:

Cured all genetic diseases Was the first time DNA was discovered Proved that all humans have identical DNA Provided the complete sequence of human DNA, enabling identification of genes and genetic variations

Question 4

Pharmacogenomics uses genomic data to:

Select the most effective drug and dosage based on a patient's genetic profile Modify a patient's DNA to cure disease Identify criminals from DNA left at crime scenes Clone organisms for research

Question 5

In a multiple sequence alignment, a conserved region across many species most likely indicates:

A region with no biological function A functionally important region preserved by natural selection A recently mutated region A region that was added by genetic engineering

Introduction to Bioinformatics

DNA Databases and Genomic Data

Major Biological Databases

Data Formats

Sequence Alignment

Pairwise Sequence Alignment Example

Global Alignment

Local Alignment (BLAST)

Genomics Applications

Applications of Bioinformatics

COVID-19 and Bioinformatics

Key Vocabulary

Bioinformatics

Sequence Alignment

BLAST

Genomics

Worked Examples

Two DNA sequences are aligned: ATGCCTGA and ATGCATGA. Calculate the percentage sequence identity.

Explain how BLAST could be used to identify a newly discovered gene's function.

A phylogenetic analysis of a gene shows that human and chimpanzee sequences differ by 1.2%, while human and mouse sequences differ by 15%. What does this tell us about evolutionary relationships?

Knowledge Check

Key Concepts Summary