Medical genomics – lecture 6 – Forces that shape the genome
Genetic code is almost universal.
Structure of genome differs in species, because there are forces that shape the
genomes of individual species. (e.g. duplication events. Multiple copies are formed
some evolve into new genes other lose their function and become pseudogenes)
Describe; how differences have appeared in the organization of genomes in the 3
domains of live
The three domains of life
1. Bacteria; unicellular. DNA organized in circular chromosome and plasmids
2. Archaea; unicellular, most are extremophiles (live in harsh environment). DNA
organized in circular chromosome and plasmids
3. Eukaryotes; unicellular, plants and animals.
Bacteria no introns, archaea some, eukaryotes a lot
Bacteria no TATA-box (promote gene transcription), archaea some, eukaryotes a lot
Variations in genome size and complexity
Genome size differs, before genome was sequenced the genome size could be
determined, because the genetic material was established (vastgesteld)
Genome complexity;
• Prokaryotes (bacteria, archaea; unicellular); as much genes as proteins
• Eukaryotes; not as much genes as proteins --> C-value paradox. Genome A is
bigger than b, but B is complexed. C-value paradox; genome size differ and
does not correlate with organism’s complexity.
This is become eukaryotes have a lot of non-coding DNA in the genome
Why do eukaryotic genomes contain more non-coding DNA
Prokaryotes have preference to delete non-coding regions. Eukaryotes doesn’t have
this.
Genome duplications in plants and animals
Genome duplications plays major force in the evolution.
Organisms can develop new functions for duplicates.
Evidence for genome duplication;
• Endopolyploidy; more than 2 sets of chromosomes (3n etc.) -->replicate the
genome without cell division.
• Polyploidy; more than 2 sets of chromosomes (3n etc.)
It is in the haploid genome also possible to found evidence for multiplication of
chromosomes. Look at blocks, matching blocks means reorganization. They
can estimate the age of duplication events. Evidence of >4 genome
duplications.
It occurs during wrong mitosis.
, Non-coding DNA
95% of human genome is non-coding DNA (this varies)
• Isochores
• Pseudogenes
• Repeats (minisatellites and microsatellites)
• Mobile elements (transposons and retroviruses)
Junk DNA; regions in the genome that do not contains any genes and are useless.
Isochores
Spots where the base-pair composition may vary in different regions of the genome
from the average.
• High content of CG; high gene density
• Low content of CG; low gene density
Pseudogenes
During the duplication there are 2 possible outcomes; it goes well (paralogs) or it has
a lot of mutations (pseudogenes, has loss of function)
2 forms pseudogenes;
1. Processed (bewerkt) (retrotransposed); lack promotor and
introns. First was mRNA --> cDNA --> incorporated into
the DNA
2. Unprocessed; can exist because of single functioning
copy of a gene is sufficient (voldoende)
Repeats
Tandem (in the same direction) repeats; repeated units of identical DNA sequences.
Often present in heterochromatin. Based on length;
1. Microsatellite; 1-6 nucleotides
2. Minisatellite; 7-100 nucleotides
Microsatellites (or simple sequence repeats SSRs)
Found in prokaryotes and eukaryotes
Varies between persons. Some have 8 others 12.
This variability is caused by slipped-strand mispairing.
The repeats have no special function (but mutations
involving in trinucleotide repeats are responsible for
different neurological diseases in humans)
Trinucleotide repeats and human disease
Special type of microsatellite is trinucleotide repeats.
Responsible for 14 neurological diseases (Huntington), these mutations found in both
coding and non-coding regions.
Huntington is caused by the protein huntingtin. In this protein there are too much
repeats of CAG, this will lead to making the wrong protein. Normally 6-25 CAGs,
disease 36-121 repeats.
Genetic code is almost universal.
Structure of genome differs in species, because there are forces that shape the
genomes of individual species. (e.g. duplication events. Multiple copies are formed
some evolve into new genes other lose their function and become pseudogenes)
Describe; how differences have appeared in the organization of genomes in the 3
domains of live
The three domains of life
1. Bacteria; unicellular. DNA organized in circular chromosome and plasmids
2. Archaea; unicellular, most are extremophiles (live in harsh environment). DNA
organized in circular chromosome and plasmids
3. Eukaryotes; unicellular, plants and animals.
Bacteria no introns, archaea some, eukaryotes a lot
Bacteria no TATA-box (promote gene transcription), archaea some, eukaryotes a lot
Variations in genome size and complexity
Genome size differs, before genome was sequenced the genome size could be
determined, because the genetic material was established (vastgesteld)
Genome complexity;
• Prokaryotes (bacteria, archaea; unicellular); as much genes as proteins
• Eukaryotes; not as much genes as proteins --> C-value paradox. Genome A is
bigger than b, but B is complexed. C-value paradox; genome size differ and
does not correlate with organism’s complexity.
This is become eukaryotes have a lot of non-coding DNA in the genome
Why do eukaryotic genomes contain more non-coding DNA
Prokaryotes have preference to delete non-coding regions. Eukaryotes doesn’t have
this.
Genome duplications in plants and animals
Genome duplications plays major force in the evolution.
Organisms can develop new functions for duplicates.
Evidence for genome duplication;
• Endopolyploidy; more than 2 sets of chromosomes (3n etc.) -->replicate the
genome without cell division.
• Polyploidy; more than 2 sets of chromosomes (3n etc.)
It is in the haploid genome also possible to found evidence for multiplication of
chromosomes. Look at blocks, matching blocks means reorganization. They
can estimate the age of duplication events. Evidence of >4 genome
duplications.
It occurs during wrong mitosis.
, Non-coding DNA
95% of human genome is non-coding DNA (this varies)
• Isochores
• Pseudogenes
• Repeats (minisatellites and microsatellites)
• Mobile elements (transposons and retroviruses)
Junk DNA; regions in the genome that do not contains any genes and are useless.
Isochores
Spots where the base-pair composition may vary in different regions of the genome
from the average.
• High content of CG; high gene density
• Low content of CG; low gene density
Pseudogenes
During the duplication there are 2 possible outcomes; it goes well (paralogs) or it has
a lot of mutations (pseudogenes, has loss of function)
2 forms pseudogenes;
1. Processed (bewerkt) (retrotransposed); lack promotor and
introns. First was mRNA --> cDNA --> incorporated into
the DNA
2. Unprocessed; can exist because of single functioning
copy of a gene is sufficient (voldoende)
Repeats
Tandem (in the same direction) repeats; repeated units of identical DNA sequences.
Often present in heterochromatin. Based on length;
1. Microsatellite; 1-6 nucleotides
2. Minisatellite; 7-100 nucleotides
Microsatellites (or simple sequence repeats SSRs)
Found in prokaryotes and eukaryotes
Varies between persons. Some have 8 others 12.
This variability is caused by slipped-strand mispairing.
The repeats have no special function (but mutations
involving in trinucleotide repeats are responsible for
different neurological diseases in humans)
Trinucleotide repeats and human disease
Special type of microsatellite is trinucleotide repeats.
Responsible for 14 neurological diseases (Huntington), these mutations found in both
coding and non-coding regions.
Huntington is caused by the protein huntingtin. In this protein there are too much
repeats of CAG, this will lead to making the wrong protein. Normally 6-25 CAGs,
disease 36-121 repeats.
