The Human Genome
Human genome – complete nucleic acid sequence
Present as DNA within 23 chromosomes pairs in cell nuclei and as a small molecule in individual
mitochondria
Human genome contains protein-coding DNA and non-coding DNA
First draft sequence completed by Human Genome Project published in 2001 – consists of 3 billion DNA
base pairs
DNA and RNA
• RNA may be hereditary material at early stage of evolution
• Genetic information stored in DNA
• DNA molecules more chemically stable, can be copied more faithfully and transmitted to daughter
cells
• In humans (and eukaryotes), DNA found mainly in chromosomes of nucleus but each
mitochondrion also has a small DNA molecule
Chromosomes
• Total length of human genome is 1m – most cells are diploid so twice this in diploid cells
• Average sized chromosome has a single double DNA helix with 140million nucleotides per strand,
4.8cm long
• Cell nucleus is only 10um diameter
• Functions
o Faithful transmission of genetic information
o Appropriate expression of genetic information
• DNA is complexed with various proteins to form chromatin
• Chromatin undergoes various levels of coiling and compaction
• Cells undergoing division, chromatids attach to centromeres and become highly condensed so
genes cannot be expressed
• Chromatids can be seen under a microscope most clearly when contracted during division
(metaphase highest resolution)
• During interphase, most chromosome regions highly extended allowing genes to be expressed
• Chromatin that is extended is called euchromatin and contains active (expressed) genes
• Heterochromatin remains highly condensed throughout cell cycle and is genetically inactive
• Can see more bands on chromosome when chromatin extended (higher resolution) – during
interphase or just at beginning of division
• Gene loci described as being within a band
o Visible band probably has 8-10million base pairs of DNA and may contain 10-100+ genes
o Every band has a number, originally numbered out from centromere
o Major, sub and sub-sub bands
▪ Centromere – point of attachment to mitotic spindle
▪ Telomere – structures to protect ends of chromosomes
▪ Heterochromatin – late replicating uniformly stained regions, often
polymorphic in size
▪ Short arm – p arm
▪ Long arm – q arm
, Gene – discrete segments 0f DNA that are used to direct the synthesis of two types of products, proteins
and RNA; a part of a DNA molecule that serves as a template for making a functionally important RNA
molecule
Coding RNA (mRNA) – contain a sequence that can be decoded to make a polypeptide sequence used in
synthesis of proteins
Non-coding RNA – do not serve as a template for making polypeptides, involved in regulation of gene
expression
Types of DNA sequences
• Human genome has single copy sequences of DNA and various sequences in multiple copies ranging
from 2 copies to millions
• Genes are present in single copy and low copy number sequences
• Repetitive DNA can be disturbed throughout genome as interspersed repeat elements or partly in
blocks of tandemly repetitive DNA
• Interspersed repeats present both between genes and within genes in introns
Class Copy number Distribution % of genome
Single copy 1 Euchromatin 50%
Low copy repeat 2-20 Euchromatin 10%
Moderate repeat 500 Single copies scattered throughout genome 25%
Highly repeated 10,000-500,000+ Clustered in heterochromatin as satellite 15%
DNA and interspersed throughout genome
Human gene structure
• Features of a gene described in
sequence of the DNA strand contains the
same sequence as the mRNA – sense strand
• Sense strand is complementary to the
antisense strand
• Transcribed portion composed of exons
and introns
• Introns are removed form primary mRNA transcript and exons spliced together to form mature
mRNA
• Introns are a lot bigger than exons
• Signal for start of translation (AUG in RNA/ATG in DNA) does not occur at first nucleotide of
transcript – 5’ untranslated region (5’-UTR) first
• ATG codon not necessarily in first exon
• Provides different opportunities for gene regulation involving alternative promoters and alternative
first exons
• Last exon contains 3’-UTR that can be quite long making last exon long
• 5’ end of gene is rich in dinucleotide CG (CpG) – CpG island
• Promoter regions are often CG-rich
• Before Human Genome Project completed, CpG islands were a good signpost for the start of a gene
Protein-coding genes
• 22,000 protein-coding genes in human genome (2% of entire genome)
• Many less complex species have similar or higher number of coding genes
o Nematode worm has a genome of 100 million base pairs with 20,470 coding genes
o Tomatoes have 35,000 coding genes
• Large number of proteins synthesised due to alternative splicing or pre-mRNA (not gene number)
• Distribution across chromosomes is non-random
• Chromosomes 1, 17 and 19 have a high gene density
Human genome – complete nucleic acid sequence
Present as DNA within 23 chromosomes pairs in cell nuclei and as a small molecule in individual
mitochondria
Human genome contains protein-coding DNA and non-coding DNA
First draft sequence completed by Human Genome Project published in 2001 – consists of 3 billion DNA
base pairs
DNA and RNA
• RNA may be hereditary material at early stage of evolution
• Genetic information stored in DNA
• DNA molecules more chemically stable, can be copied more faithfully and transmitted to daughter
cells
• In humans (and eukaryotes), DNA found mainly in chromosomes of nucleus but each
mitochondrion also has a small DNA molecule
Chromosomes
• Total length of human genome is 1m – most cells are diploid so twice this in diploid cells
• Average sized chromosome has a single double DNA helix with 140million nucleotides per strand,
4.8cm long
• Cell nucleus is only 10um diameter
• Functions
o Faithful transmission of genetic information
o Appropriate expression of genetic information
• DNA is complexed with various proteins to form chromatin
• Chromatin undergoes various levels of coiling and compaction
• Cells undergoing division, chromatids attach to centromeres and become highly condensed so
genes cannot be expressed
• Chromatids can be seen under a microscope most clearly when contracted during division
(metaphase highest resolution)
• During interphase, most chromosome regions highly extended allowing genes to be expressed
• Chromatin that is extended is called euchromatin and contains active (expressed) genes
• Heterochromatin remains highly condensed throughout cell cycle and is genetically inactive
• Can see more bands on chromosome when chromatin extended (higher resolution) – during
interphase or just at beginning of division
• Gene loci described as being within a band
o Visible band probably has 8-10million base pairs of DNA and may contain 10-100+ genes
o Every band has a number, originally numbered out from centromere
o Major, sub and sub-sub bands
▪ Centromere – point of attachment to mitotic spindle
▪ Telomere – structures to protect ends of chromosomes
▪ Heterochromatin – late replicating uniformly stained regions, often
polymorphic in size
▪ Short arm – p arm
▪ Long arm – q arm
, Gene – discrete segments 0f DNA that are used to direct the synthesis of two types of products, proteins
and RNA; a part of a DNA molecule that serves as a template for making a functionally important RNA
molecule
Coding RNA (mRNA) – contain a sequence that can be decoded to make a polypeptide sequence used in
synthesis of proteins
Non-coding RNA – do not serve as a template for making polypeptides, involved in regulation of gene
expression
Types of DNA sequences
• Human genome has single copy sequences of DNA and various sequences in multiple copies ranging
from 2 copies to millions
• Genes are present in single copy and low copy number sequences
• Repetitive DNA can be disturbed throughout genome as interspersed repeat elements or partly in
blocks of tandemly repetitive DNA
• Interspersed repeats present both between genes and within genes in introns
Class Copy number Distribution % of genome
Single copy 1 Euchromatin 50%
Low copy repeat 2-20 Euchromatin 10%
Moderate repeat 500 Single copies scattered throughout genome 25%
Highly repeated 10,000-500,000+ Clustered in heterochromatin as satellite 15%
DNA and interspersed throughout genome
Human gene structure
• Features of a gene described in
sequence of the DNA strand contains the
same sequence as the mRNA – sense strand
• Sense strand is complementary to the
antisense strand
• Transcribed portion composed of exons
and introns
• Introns are removed form primary mRNA transcript and exons spliced together to form mature
mRNA
• Introns are a lot bigger than exons
• Signal for start of translation (AUG in RNA/ATG in DNA) does not occur at first nucleotide of
transcript – 5’ untranslated region (5’-UTR) first
• ATG codon not necessarily in first exon
• Provides different opportunities for gene regulation involving alternative promoters and alternative
first exons
• Last exon contains 3’-UTR that can be quite long making last exon long
• 5’ end of gene is rich in dinucleotide CG (CpG) – CpG island
• Promoter regions are often CG-rich
• Before Human Genome Project completed, CpG islands were a good signpost for the start of a gene
Protein-coding genes
• 22,000 protein-coding genes in human genome (2% of entire genome)
• Many less complex species have similar or higher number of coding genes
o Nematode worm has a genome of 100 million base pairs with 20,470 coding genes
o Tomatoes have 35,000 coding genes
• Large number of proteins synthesised due to alternative splicing or pre-mRNA (not gene number)
• Distribution across chromosomes is non-random
• Chromosomes 1, 17 and 19 have a high gene density
