prokaryotes and extrachromosomal genetics Flashcards
extrachromosomal genetics in eukaryotes
Not based on Mendels experiments
It was found that Stem and leaf colour traits in Mirabilis plant are only inherited from the MATERNAL PARENT
Various human genetic disease traits are also only inherited from the MATERNAL PARENT e.g.:
LHON: Leber’s Hereditary Optic Neuropathy
NARP: Neurogenic muscle weakness, Ataxia, and Retinitis Pigmentosa
MERRF: Myoclonic Epilepsy with Ragged Red Fibers
Both MITOCHONDRIA and CHLOROPLASTS contain small DNA genomes
Human mitochondrial DNA is a 16,569bp CIRCULAR DNA encoding 37 genes required for mitochondrial function (energy production)
Plant chloroplast DNAs are also circular (~150kbp) and encode genes required for photosynthesis and some flower colours
The maternally inherited human disease mutations map to mitochondrial genes and affect energy production damaging tissues critically dependent on energy supply such as nerve and muscle
-> mitochondrial DNA inherited from father -> leads to specific diseases also inherited
similarly, mutations affecting photosynthesis and chlorophyll production etc. (plant green colour) map to genes in chloroplast DNA.
MELAS: Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes
LHON: Leber’s Hereditary Optic Neuropathy DEAF: Deafness and/or dystonia syndromes
NARP: Neurogenic muscle weakness, Ataxia, and Retinitis Pigmentosa
MERRF: Myoclonic Epilepsy with Ragged Red Fibers
Why are traits encoded in mitochondrial/chloroplast genomes only maternally inherited?
ONLY the sperm nucleus, and NOT the sperm mitochondria, is transferred into mammalian egg cells to create a diploid fertilised zygote
Your mitochondria, and the genetic information they contain, only come from your Mum via her egg cell
In most plant species, the cytoplasm, chloroplasts and mitochondria derive only from the maternal egg cell and not the pollen
Why are individuals with mutations in genomes within these vital organelles not DEAD?
Very often they are
However, individual organelles, cells or tissues can exhibit HETEROPLASMY with respect to organelle genome mutations allowing the organism, as a whole, to survive albeit with altered phenotype.
Organelles such as mitochondria and chloroplasts divide haphazardly, growing and fragmenting within the cell and during cell division
DNA within these organelles divide in the same way
Some have a lot more DNA/organelles and others have less
Mutation in ONE copy of an organelle genome is not always bad – other normal copies still maintain function
however, if an organelle finds itself with ONLY mutated genomes, the function of that particular organelle may be compromised
homoplasmy and heteroplasmy
The haphazard nature of organelle division means that the following can occur:
Homoplasmy - individual organelles, cells, tissues or organisms can come to contain one exclusive type of organelle genome
Heteroplasmy -a mix of normal and mutant genomes
In plants, tissue level homo- and heteroplasmy in chloroplast mutations can underly VARIAGATION in colour
Patches of leaf tissue are white and contain totally non-functional mutant chloroplasts but also normal and green, or heteroplasmic and yellow.
Heteroplasmy in human mitochondrial disease mutations often means that mum and her different offspring can exhibit variable disease severity
Here, cells in the germline-generating tissue (ovary) are heteroplasmic and pass defective mitochondria to the egg cells. The rest of the tissue has normal mitochondria. Therefore = healthy mum; sick kids.
Describe the structure and gene composition of organelle genomes and how mutations can propagate within them leading to “homoplasmic” and “heteroplasmic” organelles, cells and tissues.
cures
Human egg cell components can be micro-manipulated and transferred between gametes
“Three parent baby” IVF technologies essentially allow transplant of healthy mitochondria into a germ line
ethical conderations!
other forms of Extrachromosomal inheritance
Current endosymbionts
Prions
Mitochondria and chloroplasts contain not only their own DNA, but also maintain specific REPLICATION, TRANSCRIPTION and TRANSLATION machinery
At the level of amino acid sequence and sub-unit organisation, these systems and enzymes appear BACTERIAL
Organelle endosymbioses are ancient landmarks in eukaryote evolution – but several intracellular bacterial “infections”/endosymbioses are ongoing right now:
70% of current arthropod species have stable intracellular Wolbachia bacterial “infections” within their cells. Genes encoded in these bacteria control some host phenotypes and the bacteria are transmitted maternally like mitochondria.
Briefly explain how bacterial infections/endosymbioses and prion proteins might also be considered as types of extra-chromosomal inheritance in eukaryotes. - prions
A rare class of heritable “mutations” in yeast (and other fungi) represent structural changes in a PROTEIN called a PRION rather than a change to bases in DNA
PRION- a normal cellular protein (often regulating other genes) but with TWO distinct physical forms: a normal form and an altered form that arise and interconvert spontaneously, but rarely.
If a [PRION+] protein form meets a molecule of the [PRION-] form, the [PRION-] gets converted to [PRION+] and the two [PRION+] factors can form a larger infectious protein AGGREGATE
The [PRION+] state can eventually dominate (converting all the available [PRION-] protein forms) leading to a complete switch in function of the original protein
The [PRION+] aggregates can persist and spread in both cytoplasm and nuclei and move from cell to cell during mitosis and meiosis
The prion and its phenotype therefore appears HERITABLE and transmitted from generation to generation
In fungi, environmental stress can lead to production of protein ”chaperones” which re-fold [PRION+] aggregates back to their normal state
Fungal prion systems appear to allow long-term heritable but reversible changes in cell function.
Prion proteins also exist in humans. They spread and transmit within cells and tissues and underly pathogenic states such as Kuru, Alzheimer’s disease and BSE (above). Human prion states do not transmit during meiosis fortunately
Explain the implications of mitochondrial genome mutations in terms of human disease, and briefly describe the therapeutic option arising from three parent IVF technology.
prokaryote reproduction and DNA shuffing
If prokaryotes only engaged in asexual/clonal reproduction, without any form of recombination, they would be unable to prevent an increase in “mutational load”
Although prokaryotes do not do MEIOSIS, they can still shuffle chunks of DNA to explore new combinations of genes and to “shuffle” good and bad alleles of genes(mutations).
They draw on three general features to facilitate what we observe as: Prokaryote Genetics
1. Prokaryotes are not always simple, single cells
2. Prokaryote genes can exist on chromosomes and also on extra chromosomal plasmids
3. Prokaryotes can exchange genes between cells via 5 methods
- Prokaryotes are not always simple, single cells
Prokaryotes can DIFFERENTIATE their cells to:
collect and distribute nutrients
adhere to, or penetrate surfaces
create protective goop
swim
disperse spores
e.g., Bacillus:
surfactin producer
miner
competent cell
endospore
cannibal
matrix producer
motile cell
dead cell
Many prokaryote cells adhere after binary fission to create AGGREGATES of cells with different mutually supportive functions which resemble complex tissues. When they accumulate on surfaces we refer to them as BIOFILMS.
aggregates can form from members of different species forming symbiotic or syntropic consortia of microbes each performing particular biochemical tasks and sharing metabolites
- Prokaryote genes can exist on chromosomes and also on extra chromosomal plasmids
Prokaryote cells often also contain extra-chromosomal DNA molecules called plasmids
As well as the chromosome Prokaryotic plasmids are also circular, gene dense DNA molecules but much smaller than the chromosome (~2 Kbp –500 Kbp in size)
Plasmids can occur at many copies per cell
Many different types of plasmid can be found in the same species but varying according to geographical location
Different types of plasmid can sometimes co-exist in the same cell.
Plasmids contain useful eg. Antibiotic resistance, but not essential genes as well as junk while chromosomal genes contains essential genes and junk
- Prokaryotes can exchange genes between cells vie 5 methods
normal bidirectional DNA replication
Used to copy both chromosomes and plasmids during prokaryotic cell division
Both prokaryotic chromosomes and plasmids have ORIGINS OF REPLICATION or ori sequences which provide an
initiation site for host cell replication enzymes
Prokaryotic replication forks progress around circular DNAs in opposite directions* eventually meeting to create two daughter circles
- Prokaryotes can exchange genes between cells vie 5 methods - conjugation
Up to 25% of plasmids found in nature are “CONJUGATIVE”; they carry a second ori called oriT, within a cluster of TRANSFER genes (denoted tra or trs)
Conjugation- precisely choreographed replicative transfer of plasmid DNA from one cell to another
Transfer genes encode plasmid-specific replication enzymes which recognise oriT and catalyse a cell-to-cell replicative transfer of the plasmid called CONJUGATION
This process is also sometimes termed “bacterial mating”
nomenclature:
Cells lacking a specific conjugative plasmid are termed: “Recipient” strains;
Plasmid - (“minus”) strains. E.g., “F.”
Cells that harbour a specific conjugative plasmid are termed: “Donor” strains;
Plasmid + (“plus”) strains. E.g., “F+”
CONJUGATION: Specific tra/trs genes on the plasmid encode proteins called PILINS that extrude from the cell to form long
tubes called PILI (PILUS = singular)
CONJUGATION: The pilus specifically recognises and adheres to the surface of plasmid “minus”/”recipient” strains and creates a channel between the two cells
The channel enzymes catalyse transfer of a single plasmid DNA strand from the “plus” to the “minus” strain.
ssDNA production initiates from the “origin of transfer” oriT
the ssDNA transferring to the “minus” strain and the ssDNA remaining in the “plus” strain are both re-copied back into dsDNA
at completion of the process, the plasmid
“minus” cell is converted into a plasmid “plus” cell!
- Prokaryotes can exchange genes between cells vie 5 methods - transposition
Groups of prokaryotic genes are often embedded within stretches of DNA which behave as TRANSPOSIBLE ELEMENTS
TRANSPOSABLE ELEMENTS are MOBILE DNA sequences that are able to JUMP (“transpose”) from one location within a DNA molecule to another within a cell
The simplest types of transposable elements in prokaryotes are called INSERTION SEQUENCES (IS) -of which there are many different types
An IS contains a single gene (tnp) encoding molecules of a TRANSPOSASE enzyme which recognises two flanking short DNA sequences which are identical but inverted with respect to each other – called: INVERTED REPEATS
The transposase enzymes catalyse TRANSPOSITION - A DNA sequence “jump” reaction
These jump events are not common but do occur at a significant rate: 1 jump every 1000 – 10,000 cell divisions in bacteria.
Some transposable elements jump from one region of DNA to another (NON-REPLICATIVE transposition)
Other transposable elements are REPLICATIVE - they create a new COPY of the element during the jump
TWO Insertion Sequences of the same type can easily end up on either side of a normal prokaryotic gene/group of genes
transposase enzymes can get confused over which PAIR of inverted repeats to act on - and can jump both ISs plus the intervening gene
A Transposable Element carrying extra genes is called a TRANSPOSON (Tn)
