Transcript mutation - ahsbognasbi4u

MUTATION
 a permanent change in the nucleotide sequence
of a cell’s DNA
 can be passed on to daughter cells
 typically neutral or harmful, rarely beneficial
►allow
species to change and adapt over time
►only those adapted to their environment will survive
► Multicellular
mutations:
organisms have two types of
 Somatic mutations
► passed
on during mitosis, but not to subsequent generations
 Germ-line mutations
► occur
in cells that give rise to gametes, passed to subsequent
generations
Mutations Can Be:
►
spontaneous
 take place naturally as a result of normal
molecular interactions (ex. DNA pol made a
mistake, 1/10–9)
►ex.
DNA replication, transposons (jumping genes)
► induced
 caused by agents outside the cell
 mutagen: a substance that increases the rate of
mutation
►
ex. nitrous acid (HNO2)
 can turn C in DNA into U
►
ex. benzpyrene, a component of cigarette smoke
 adds a large chemical group to G, making it unavailable for base pairing
►
ex. ionizing radiation (X-rays)
 produces highly reactive chemical species called free radicals, which can
change bases in DNA to unrecognizable (by DNA polymerase) forms
 It can also break the sugar–phosphate backbone of DNA, causing
chromosomal abnormalities
 UV is absorbed by thymine in DNA, causing it to form interbase covalent
bonds with adjacent nucleotides. This, too, plays havoc with DNA
replication.
► mutagens
 physical
►ex.
X-rays, UV
 chemical
►ex.
nitrites, gasoline fumes, cigarette smoke
Types of Mutations
1. single-gene mutations

a)
point mutation (mispairing)


b)
changes in nucleotide sequence of one gene
most frequent type
single base pair is substituted/inserted/deleted
frameshift mutation (strand slippage)

change of reading frame
► effect
can be minor, or not…
 depends on final consequence
(reading the code)
Nonsense
Missense
Silent
Neutral
i) silent mutation
► aa
sequence stays the
same
ii. missense mutation
► alters
aa sequence
of a protein
Single base change in hemoglobin gene causes
sickle cell anemia
wildtype
allele
wildtype
phenotype
mutant
allele
mutant
phenotype
iii. nonsense mutation
► mutation
that
inserts a “stop”
earlier than it was
iv. frame-shift mutation
► reading
frame shifts
►
Base substitutions (point mutations) ,insertions, and
deletions
Types of Mutations
2. chromosome mutations
 changes in chromosomes, can involve many
genes
 usually a consequence of cross-over gone
wrong (meiosis)
So…if this is dangerous, how do you
fix it?
ERROR CORRECTION
►
a human cell can copy its DNA in a few
hours
 if you were to type this, 1 letter per second, it
would take you close to 100 years
 200 books at 1000 pages each…
► error
total)
rate: 1/1 billion pairs (3 billion pairs
MECHANISMS OF REPAIR
DNA polymerase I and DNA polymerase II
- both proof-read and “fix” mistakes as new
DNA is being made
1.


99% of mistakes are caught this way
incorrect base is taken out, correct added
2.
-
Mismatch repair
similar in prokaryotes and eukaryotes
protein group replaces mismatched
nucleotide with correct one
Mutations and Evolution
► typically
►allow
neutral or harmful, rarely beneficial
species to change and adapt over time
• random accumulation of mutations (in the
extra copies of genes) can lead to the
production of new useful proteins and new
functions!
World map of human migrations, with the North Pole at center. Migration patterns are based on
studies of mitochondrial (matrilinear) DNA. Dashed lines are hypothetical migrations.
Numbers represent thousand years before present, with 2-4% mutation rate per 1 million years.
Our sense of smell sucks…
► 80 genes were lost in the human lineage after separation
from the last common ancestor with the chimpanzee. 36 of
those were for olfactory receptors.
Our immune systems are amazing, allowing us to live in very
large groups
► Genes involved in chemoreception and immune response
are overrepresented
We’re the “hairless ape”
► A gene for type I hair keratin was lost in the human
lineage. The loss of that particular gene may have caused
the thinning of human body hair. The gene loss occurred
relatively recently in human evolution—less than 240,000
years ago.
Our jaws are not all that useful
►
Stedman et al. (2004) stated that the loss of the
sarcomeric myosin gene MYH16 in the human lineage led
to smaller jaw muscles.
►
They estimated that the mutation that led to the
inactivation (a two base pair deletion) occurred 2.4 million
years ago, predating the appearance of Homo
ergaster/erectus in Africa.
 The period that followed was marked by a strong increase in
cranial capacity, promoting speculation that the loss of the gene
may have removed an evolutionary constraint on brain size in the
genus Homo.
► Compared
with
chimps, humans have
evolved weak jaw
muscles and jaw bones
– cooked food and
your brain?
► The
expansion of the
human brain may have
involved a snowball
effect, in which initial
mutations caused
further mutations that
enhanced the brain
even more
► Humans'
big brains
require extra energy –
three mutations may
have helped meet that
demand
► In
6 million years, our
diet gradually changed
from fruit and leaves
to starchy grains.
Genes involved in
digestion offer a
timeline to those
dietary changes
We can TALK
► Humans and Neanderthals also share the FOXP2
gene variant associated with brain development
and with speech in humans, indicating that
Neanderthals may have been able to speak.
► Chimps
have two amino acid differences in FOXP2
compared with human and Neanderthal FOXP2
► You
can teach a chimp
tricks, but it won't ever
talk. The human
"language gene" has
helped us learn the
rules of speech and
maybe even grammar