Human Genome Biology

Physical Organization of the Human Genome

• The human genome is contained within two distinct compartments: the nucleus and the mitochondria.
• The nucleus contains about 20,000 to 25,000 genes encoded by DNA, which is organized into linear chromosomes.
• Mitochondrial DNA contains 37 genes essential for normal mitochondrial function and is exclusively of maternal origin.

Information Organization

• The haploid genome consists of 3.0 x 10^9 bp of DNA, divided into 23 chromosomes.
• The entire haploid genome contains sufficient DNA to code for nearly 1.5 million pairs of genes.
• The human genome has only about 20,000 to 25,000 genes, similar to the number of genes in a fruit fly.
• Human protein-coding genes appear to produce more than one protein product by alternative splicing.

Gene Classification

• Genomic DNA can be classified into two categories: unique or single copy, and repetitive sequence DNA.
• Unique DNA sequences encode information for specific protein products.
• The 20,000 to 25,000 genes within the human genome can be divided into four general categories:
  • Approximately 5,000 genes involved with genome maintenance.
  • Nearly 5,000 genes involved with signal transduction.
  • 4,000 genes involved with general biochemical functions.
  • The largest portion, 9,000 genes, involved in other activities.

Repeat Sequences

• Repeat sequences do not encode proteins but make up at least 50% of the human genome.
• These sequences are important for chromosome structure and dynamics.
• Repeat sequences can be classified into two main classes: satellite DNA and LINEs and SINEs.
• Satellite DNA is highly repetitive and tends to be clustered and repeated many times in tandem.
• Satellite DNA is categorized according to the number of base pairs within the repeat sequence:
  • Alpha satellite: 171 bp sequence.
  • Minisatellite: 20 to 70 bp in length.
  • Microsatellite: repeat units only 2, 3, or 4 bp in length.

LINEs and SINEs

• LINEs and SINEs are unclustered sequences found interspersed with unique sequences.
• They are transcribed into RNA and can be grouped according to their size.
• LINEs (long interspersed elements): 7,000 bp, 20 to 50,000 copies.
• SINEs (short interspersed elements): 90 to 500 bp, about 100,000 copies.

Gene Structure and Function

• A gene is the complete sequence region necessary for generating a functional product.
• This encompasses promoters and control regions necessary for transcription, processing, and translation.
• About 2% of the genome encodes instructions for the synthesis of proteins.
• Genes appear to be concentrated in random areas along the genome, with vast expanses of noncoding DNA between them.

Pseudogenes

• Pseudogenes are a type of evolutionary relic, indicating that the human genome is continually undergoing change.
• There are two main types of pseudogene:
  • Conventional pseudogene: a gene that has been inactivated due to mutation.
  • Processed pseudogene: derived from the mRNA copy of a gene by synthesis of a DNA copy which subsequently re-inserts into the genome.