BIOL1020 - Lecture 14 - Phenotypic variation and inheritance

inheritance or heredity:

> some traits (physical or biochemical characteristics) are heritable - they are passed on from one generation to the next.

>related individuals look more alike than unrelated ones.

the phenomenon by which offspring resemble their parents

why offspring are not identical

> inherited characteristics are determined by genes

all individuals of a species have the same base set of genes

variation is due to gene mutation

variants of the same gene - alleles - account for variant traits.

> genotype is the allelic constitution of an individual (can refer to one, a few, or many loci)

the trait value of an individual (under the combined influence of genotype an environment)

> e.g., brown eyes/blue eyes

changes in genotype arise from mutation of genomic DNA

> mutations are changes in the DNA sequence

> point mutations - single nt changes

insertions or deletions

translocations, deletions or duplications - large scale chromosomal changes.

- silent, mis-sense and non-sense

mutations can be in the coding region or the non-coding region of DNA.

mutations can occur in somatic cells or germ cells.

a reciprocal translocation

> the ABL oncogene from chromosome 9 is replaced with a segment from chromosome 22.

>chromosome 22 now has the ABL gene and is now called BCR-ABL.

>this is called the Philadelphia chromosome.

>causes an over proliferation of cells, thus leukaemia

> spontaneous mutations result from internal cellular processes

- mis-incorporation of nucleotides during DNA replication

- these are mainly due to very rare errors during DNA replication (and the molecular DNA repair machinery in the cell takes care of most of them)

- in humans mutation rate is ~ 1 in every 2x10^8 base, or about 100-200 mutations accumulating from one generation to the next.

- errors during meiosis causing chromosomal abnormalities (wrong pairing up of homologous chromosomes)

induced mutations result from external mutagens

- e.g., UV light, mutagens such as chemicals (represses repair)

> loss of function mutations

- interfere with the ability of a gene to code for a fully functioning protein

- or can be regulatory mutations affecting gene’s promoter

- mis-sense - changes amino acids

- non-sense - produces a stop codon

silent mutations

- have no affect on protein function

gain of function

- these are usually dominant and result in a protein with altered functionality.

sickle cell disease:

> in the gene sequence for hemoglobin, an A is swapped for a T, causing the sequence to change from thr pro glu glu to thr pro VAL glu

> this single nt change leads to sickle cell anemia

> somatic mutations occur in the soma, the cells of the boy not involved in producing sex cells

germ line mutations happen in the germ cells, and are therefore inherited.

most mutations occur in the soma

cancer

> cancer is the outcome of mis-regulation of the cell cycle caused by genetic mutations

some forms of breast cancer and ovarian cancer. E.g., BRC1 and BRC 2 genes.

> reproduction

> bacteria have other strategies

> they are highly genetically variable

mutations and rapid reproduction (which propagates new mutations clonally)

horizontal DNA transfer and genetic recombination

> spontaneous mutation occurs in E.coli gene 1 x 10^7 per cell division

but 2 x10^10 new cells each day in a persons intestine.

therefore 2000 bacteria with mutations in a given gene each day

note that the 2000 bacteria may carry mutations in the same gene, but they are not the same mutation.
E.coli genes, therefore up to 4300 x 2000 = 9 million E.coli variants per human host per day

CONJUNCTION

> transfer by direct cell to cell contact via a pilus and a conjugative plasmid

TRANSFORMATION

> uptake and incorporation of naked DNA

TRANSDUCTION

> transfer of chromosomal or plasmid DNA from cell to cell by a bacterial virus (bacteriophage)

> sex pili allow bacteria to exchange DNA via conjunction (the closest a bacterium can get to sexual reproduction)

Plasmid mediated DNA transfer

conjugative plasmids are capable of initiating plasmid transfer from cell to cell by direct contact - conjugation (no ‘chromosomal’ DNA gets exchanged)

plasmids that promote conjugation may be referred to as fertility factors (or F - plasmids), they initiate the pilus formation and the transfer of its own copy into the recipient cell.

CHARACTERISITICS:

F plasmids are large (often > 25kbp)

broad host range (horizontal gene transfer between species)

often contain multiple antibiotic resistance genes

learn diagram from Grace

> transformation with naked DNA

some bacteria take up DNA from the environment and integrate it into their chromosome.

e.g., Streptococcus pneumoniae

limited DNA of same (or closely related) species

relies on “recombination” with “homologus” DNA sequence in the genome also used today to transform plasmid DNA into bacteria.

griffith in the 1920s

> learn heather’s diagram, but pretty much mediated via bacteriophages

> mechanism of DNA transfer within the cell.

transposons are lengths of DNA that can ‘jump’ from one site to another

contain genes that promote integration and ‘excision’

- can integrate into the DNA - genomic or plasmid

- can cut themselves out of the DNA - excise

- can reintegrate somewhere else

many transposons contain genes that encode for resistance to antibiotics

when a transposon is carried on a conjugative plasmid these resistance genes can spread rapdily throughout bacterial populations

common in hospitals (antibiotic rich environments)

eukaryotes and prokaryotes

mobile genetic elements

transposition genes can insert themselves around the gene for antibiotic resistance, then when they excise again, they carry the sandwiched antibiotic-resistance gene along with them.