Genomics and Proteomics

Core Concepts

What a genome is

A genome is all of the DNA in an organism's cells (for eukaryotes, usually meaning the nuclear DNA; organelles such as mitochondria have their own small genomes). Genome size varies enormously and does not track complexity — an onion's genome is larger than a human's (a commonly taught example of the "C-value paradox"). What matters more than size is content: genes, regulatory sequences, and other functional elements.

How genomes are sequenced and analyzed

Modern sequencing reads short stretches of DNA, and computers assemble the millions of short reads into chromosomes using overlapping ends. The Human Genome Project itself was a race between public laboratories and a private company; its completion in 2003 (commonly taught) marked the point at which a reference human sequence was declared essentially complete. Sequencing a person's genome today takes days and costs a small fraction of what the first genome cost — a trajectory worth remembering: sequencing costs have fallen dramatically since the first human genome.

Bioinformatics: making sense of sequences

Raw sequence is useless without analysis. Bioinformatics uses computers to store sequences in public databases (such as GenBank at the NCBI), search for similar sequences (the BLAST program), and annotate genomes — finding genes by looking for open reading frames (ORFs: stretches from a start codon to a stop codon) and by comparing with genes already known from other species. Similarity between sequences is evidence of shared ancestry, so BLAST is also an evolutionary tool.

Metagenomics

Most microbes cannot be grown in the laboratory, so classic microbiology could not study them. Metagenomics sequences DNA directly from environmental samples — soil, seawater, the human gut — and identifies the organisms present from their DNA alone. This approach revealed the vast diversity of the microbiome and changed our picture of microbial life.

The proteome is bigger than the genome

One gene does not equal one protein. Alternative splicing lets a single gene produce multiple different mRNAs and therefore multiple protein versions. Post-translational modifications — adding phosphate groups, sugars, or lipids, or cutting the protein — further change what a protein does and when. A human cell's proteome is therefore far larger than its gene count, and it changes with cell type, developmental stage, and conditions. Proteomics captures that dynamic picture using techniques such as two-dimensional gel electrophoresis (separating proteins by charge and size), mass spectrometry (identifying proteins by mass and fragments), and protein microarrays.

Genomics and proteomics in medicine

Tumor genomes are sequenced to find driver mutations and match patients to targeted drugs; pharmacogenomics asks how a person's gene variants affect drug metabolism and dosing; protein biomarkers in blood help diagnose and monitor disease. These applications raise real privacy questions — who may see your genome, and what may they do with it? — addressed in the United States by laws such as GINA, which prohibits genetic discrimination in health insurance and employment (commonly taught).

Common Confusions