Genetics Flashcards
define ‘atavism’
Atavism is the tendency to revert to ancestral type. In biology, an atavism is an evolutionary throwback, such as traits reappearing which had disappeared generations before. Atavism does not fit with the theory of mixing bloods.
what is Mendel’s First Law?
This is the law of segregation. During gamete formation, the alleles for each gene segregate from each other so that each gamete carries only one allele for each gene.
what is Mendel’s Second Law?
This is the law of independent assortment. During gamete formation, the segregation of alleles at one locus is independent to that at any other.
if the number of heterozygous loci is denoted by n, how many gamete types are there?
2^n
if the number of heterozygous loci is denoted by n, how many phenotypes are produced in the F2 generation?
3^n
define ‘heterosis’
Otherwise known as hybrid vigour, heterosis is the improved or increased function of any biological quality in a hybrid offspring.
define ‘codominance’
the phenotypic effects of a gene’s alleles are fully and simultaneously expressed in the heterozygote
give an example of codominance
sickle-cell anaemia - both normal and mutant haemoglobin types are produced in the heterozygote
define ‘multiple allelism’
more than two alleles at a single locus
give some examples of multiple allelism
human eye colour
clover leaf patterns
ABO blood system - A has n-acetyl galactosamine antigen; B has galactose antigen; AB has both; O has neither
define ‘lethal alleles’
alleles that are lethal in the homozygous ie. the dominant allele for the particular characteristic is recessive for viability
give some examples of lethal alleles
allele responsible for the yellow coat colour in mice
Manx cats
Brachydactyly
Achondroplastic dwarfism
define ‘pleiotropy’
the production by a single gene of two or more apparently unrelated effects
give some examples of pleiotropy
all blue-eyed white cats are deaf (due to the role of melanin in the ear)
tabby cats are unusually aggressive
sickle-cell anaemia causes many health complications, as well as conferring resistance to malaria
Drosophila white eye has an effect on the shape of spermatogonia (due to a mutation in a transporter protein that functions in many tissues)
define ‘gene interaction’
the collaboration of several different genes produces one phenotype
give some examples of gene interaction
sex limitation (due to the effects of testosterone) mouse coat colour
what does the A locus control in mouse coat colour?
A locus - determines the distribution of colour in hair shaft
A- = yellow band (agouti)
aa = no yellow band (black)
define ‘incomplete dominance’
the expression of the heterozygote is an intermediate between the dominant homozygotes
give some examples of incomplete dominance
Japonica mirabilis - cross between red and white produces pink flowers
Tay Sachs - heterozygotes have intermediate levels of the enzyme hexosaminidase A
Mendel’s peas were round or wrinkled depending on their levels of starch-branching enzyme; peas heterozygous at this locus appear round but have intermediate levels of the enzyme
what does the B locus control in mouse coat colour?
B locus - codes for the colour of the hair
B- = black
bb = brown
explain the interaction between the A and B loci in mouse coat colour
A-B- = agouti A-bb = cinnamon aaB- = black aabb = brown
what does the C locus control in mouse coat colour?
C locus = determines presence or absence of pigment
C- = pigmented
cc = albino
what does the D locus control in mouse coat colour?
D locus - controls expression of pigment (modifying locus)
D- = full expression of coat colour
dd = pale/milky colour
what does the S locus control in mouse coat colour?
S locus - controls pigment distribution on the body
S- = not spotted
ss = piebald
define ‘complementation’
two strains of an organism with different homozygous recessive mutations produce the same phenotype
give some examples of complementation
foxglove petal colour
Drosophila eye colour
deafness in humans
what are the phenotypes of the F1 and F2 upon crossing fox gloves?
F1 phenotype - all purple
F2 phenotype - 9 purple and 7 white
what is a complementation test?
To test for complementation, cross two homozygotes and observe the phenotypes of the resulting offspring. If there is complementation between the two alleles, the phenotype will revert to the wild type, since the offspring will be heterozygous at both loci.
define ‘epistasis’
an interaction between nonallelic genes in which the genotype at one locus affects the expression of alleles at another locus
define ‘chromosome puff’
a swelling at a site along the length of a polytene chromosome; the site of active transcription
define ‘polytene chromosomes’
over-sized chromosomes that have developed from standard chromosomes and are commonly found in the salivary glands of Drosophila melanogaster
what is a reciprocal cross?
A reciprocal cross is a pair of crosses between a male of one strain and a female of another, and vice versa
define ‘aneuploidy’
the deviation from an exact multiple of the haploid number of chromosomes
define ‘nondisjunction’
the failure of chromosomes to separate and segregate during meiosis
what was the result of a cross between a male with red eyes and a female with white eyes whose gametes had undergone nondisjunction?
gametes of male: X Y
gametes of female: XX O
offspring: XXX (dies) XXY (white-eyed female) XO (red-eyed male) YO (dies)
how is sex determined in Drosophila?
by the number of X chromosomes
1 X = male; 2 Xs = female
how is sex determined in humans?
by the presence of a Y chromosome that determines maleness
which genotypes are viable in humans?
XO and XXX are viable and female; XXY is viable and male; YO is not viable
what are the gametal genotypes of birds and butterflies?
males are homogametic WW and females are heterogametic WZ
describe the transmission of recessive sex-linked alleles
transmission through females; mainly affects males; for an affected male, all his daughters are carriers but none of his sons are affected
give some examples of recessive sex-linked diseases
Duchenne muscular dystrophy
Haemophilia
colourblindness
Lesch-Nyhan syndrome (disease of purine metabolism; low IQ, self-mutilation)
give an example of a dominant sex-linked disease
vitamin D-resistant rickets
describe the transmission of dominant sex-linked alleles
transmission through females and through males; males only transmit disease to daughters; females transmit disease to half of daughters and half of sons
what is Lyonisation?
the inactivation of an X chromosome early in development as a dosage compensation mechanism, resulting in the production of a Barr body
what is a Barr body?
a small, densely staining structure in the cell nuclei of females, consisting of a condensed, inactive X chromosome
give some examples of mosaicism
every adult female is a mosaic
eg. tortoiseshell cats - patches of orange and black fur; sex-linked red-green colourblindness
how does dosage compensation occur in Drosophila?
all X chromosomes are switched on, but those in males are set at an activity twice that of those in females
what can dosage compensation lead to in Drosophila?
leads to sex lethality, in which different alleles kill either the male or female depending on the under- or over-activation of genes on the X chromosome
define ‘genetic linkage’
the tendency of alleles that are located close together on a chromosome to be inherited together
who investigated coupling in sweet peas?
Bateson and Punnett
give an example of a pair of characters that Bateson and Punnett investigated
the flower colour and pollen grain length of sweet peas
what experimental abnormality is found in the case of linkage?
a parental excess and a recombinant deficiency
what is the problem of the Mendel design of cross to analyse coupling?
- phenotypically identical classes could disguise genetically heterogeneous ones
- it is also statistically inefficient
what is the Mendel design of cross?
selfing or intercrossing the F1 to produce the F2
why is the Mendel design of cross statistically inefficient?
- small numbers mean that a large deviation of observed away from expected is required to attain any significance with the 9:3:3:1 ratio of independent assortment
- it is more efficient to have a 1:1:1:1 ratio
what is a test cross?
an organism of dominant phenotype, but unknown genotype, is crossed with an organism of recessive phenotype (and genotype)
what is a back cross?
a hybrid organism is crossed with an organism genetically identical to its parents
what is demonstrated by a 9:3:3:1 ratio obtained by a Mendel cross?
independent assortment of alleles at two loci
how was it verified that the differences in expected ratios were not due to some adverse interaction of the mutations?
mutant/wildtype alleles were arranged in repulsion where they had previously been in coupling, giving the same result
what was Morgan’s hypothesis about coupling?
Morgan believed that the coupling was due to the physical proximity of the loci rather than due to the properties of the mutants themselves
which scientist investigated linkage using Drosophila?
Thomas Hunt Morgan
what are the subphases of prophase?
leptotene, zygotene, pachytene, diplotene, diakinesis
what occurs during leptotene?
chromosomes become visible as beaded threads
what occurs during zygotene?
- each homologous chromosome finds its pairs and lies alongside it
- the chromosomes are progressively ‘zipped up’ during synapsis to form a bivalent/tetrad, linked by a synaptomenal complex
what occurs during pachytene?
the paired structures condense and wrap around one another
what occurs during diplotene?
the tetrad opens out following the physical exchange of materials between the chromosome arms through the formation of chiasmata
what occurs during diakinesis?
the chromosomes contract and move towards a metaphase plate
what is a synaptomenal complex?
a protein structure that forms between homologous chromosomes and is thought to mediate chromosome pairing, synapsis and recombination
what is a tetrad/bivalent?
a pair of associated homologous chromosomes held together by a complex and formed during synapsis
what is the highest value that the frequency of recombination can assume?
50%
what is signified by a recombination frequency less that 50%?
the genes are on the same chromosome ie. they are linked
why doesn’t a recombination frequency of 50% prove that the genes are on separate chromosomes?
the genes could be far apart on the same chromsome and so display significant free recombination
what proof was provided by linkage that genes are located on the chromosomes?
number of linkage groups = number of chromosomes
who constructed the first genetic linkage map?
Alfred Sturtevant
what is a map unit?
a recombinant frequency of 1%
what cross is carried out in order to construct a linkage map?
a three-point cross in which triple heterozygotes are backcrossed to triple mutants
how can the order of the loci be established?
by comparing the parentals and double recombinants
what is the main limitation of the three-point cross?
it only works over short segments of chromosome, when one can reasonably assume that any recombinant genotype represents just 1 (not 3, 5 or 7) crossover events
what is the phenotypic result of an odd and even number of crossovers?
an odd number of crossovers gives a recombinant phenotype and an even number gives a parental phenotype
what is chiasma interference?
the influence of a chiasma on the probability of occurrence of another in close proximity
what is the effect of a positive chiasma interference?
a reduced probability of adjacent chiasma formation
how is a double recombinant frequency calculated, assuming independent assortment?
double recombinant frequency = recombinant 1 frequency x recombinant 2 frequency
what is the coefficient of coincidence?
measures strength of interference
= 1 - [observed / expected]
which chromosome is the smallest?
chromosome 21
define ‘metacentric’
the centromere is at the middle of the chromosome
define ‘acentric’
the centromere is to one side of the chromosome
define ‘telocentric’
the centromere is at one end of the chromosome
what is Feulgen reagent?
- DNA-binding chemical
- DNA is stained red
- semi-quantitative - intensity of dye can be measured to calculate amount of DNA
what is an ideogram?
schematic representation of chromosomes showing the relative size and banding patterns of each
what do dark bands signify?
heterochromatin - tightly-coiled DNA with few active genes and more A-T base pairs; found around the centromere and on the Y chromosome
which staining technique results in G-banding?
Giemsa staining; binds to phosphate groups of DNA, particularly in regions rich in A-T base pairs, to form an ideogram of dark and light bands
what distinguishes a particular chromosome?
- size
- centromere position
- arrangement of bands
what is endomitosis?
division of chromosomes that is not followed by nuclear division and that results in an increased number of chromosomes in the cell; produces polytene chromosomes
T/F - there is one gene per band
F - there are several genes within each band
what is FISH?
fluorescent in-situ hybridisation; identify the sequence of the particular gene product and manufacture a probe and its mirror image, labelled with fluorescent dye
what is somatic cell hybridisation?
- grow cell lineages in the laboratory
- make mixed cultures eg. of human and mouse cells
- treat with a virus eg. inactivated Sendai virus
- sometimes the cells fuse to form a somatic cell hybrid containing chromosomes from both species
- select for hybrid cells using a specific poison which only the hybrid cells survive
why is the (inactivated) Sendai virus used in somatic cell hybridisation?
the virus has two attachment sites that force cells to sit close to one another
how are hybrid cells selected for in somatic cell hybridisation?
- one cell lineage is deficient in one enzyme required to break down a particular poison
- the other cell lineage is deficient in another
- the poison requires both enzymes to be broken down
- only hybrid cells will have both enzymes and will survive
explain what can be identified by observing chromosomes ‘spat out’ by hybrid cells
- hybrid cells often spit out human chromosomes
- by considering phenotypic changes, the location of the particular chromosomes can be determined
how can parts of the human chromosome be integrated in the hybrid genome?
a particular chromosome can be fractionated by irradiation and added to culture; if a chromosome part is integrated, it can be inferred that there must be human genes located at the site of integration
define ‘haplotype’
a collection of alleles in a cluster of tightly-linked genes on a chromosome that are likely to be inherited together
what is haplotype mapping?
- aims to describe common patterns of human genetic variation
- identification of single nucleotide polymorphisms (SNPs)
- shortcut to full genome sequencing, since blocks can be identified by just one or two SNPs
- data presented as a Manhattan Plot
what is GWAS?
genome-wide association study; examination of many common genetic variants in different individuals to explore association with particular diseases
define ‘linkage disequilibrium’
the occurrence of combinations of genes in non-random proportions
what is unique about the Y chromosome?
almost no crossovers with the X chromosome except at each end; its haplotype is preserved with no recombinations
list some condition-dependent mutants and give examples
- heat-sensitive mutant eg. Drosophila
- light-sensitive mutant eg. artic hares (genes for pigment switched off as days shorten) and leaves (change in pigmentation as days shorten)
- nutritional-dependent mutant eg. Phenylketonuria
what is pharmacogenetics?
the branch of pharmacology that investigates the effect of genetic factors on reactions to drugs
give some examples of pharmacogenetic cases
- porphyria - usually mild/unnoticeable symptoms but barbiturate drugs precipitate symptoms
- 10% of the population lack the enzyme to metabolise codeine into morphine and so gain no relief from its administration
- the Leiden allele increases the risk of venous thromboembolism 6x
early contraceptive pills increased the risk 3x
those with the Leiden allele on the contraceptive pill had an increased risk 35x
explain the age-related effect of Huntington’s
autosomal dominant disease with a delayed age of onset means that an individual is unable to verify whether or not they have the disease for many years
who popularised the concept of regression towards the mean?
Francis Galton
what is the concept of regression towards the mean?
offspring measure closer to the average of the population than their parents do, rather than to measure as an exact intermediate between their parents
explain how some diseases present themselves related to a threshold
many diseases do not initially appear quantitative but have an underlying trait that is normally distributed and that only affects those over a certain threshold with the disease
eg. stoke - blood pressure
how many genotypes and phenotypes are available from 5 different loci, each with two possible alleles, + and - ?
there are three possible genotypes at each locus: ++,+-,–
number of genotypes = 3^5 = 243
but there are only 11 different phenotypes
define ‘mean’ and ‘variance’
mean = a measure of central tendency variance = a measure of spread
how is the variance calculated?
variance = Σ(x- x̄ )^2 / n
explain the association between phenotype, genotype and environment
phenotype = genotype + environment + genotype-environment interaction P = V(G) + V(E) + V(GE)
how is broad-sense heritability calculated?
H^2 = V(G) / V(P) = V(G) / V(G) + V(E) + V(GE)
what is broad-sense heritability?
the proportion of variation due to genetic variation;
a high heritability can be due to shared genes, shared environments or both
give an example of broad-sense heritability
- Achillea millefolium (yarrow plant) grows from sea level to 10 000 feet
- much variation in height at each elevation
- very different responses of genotype at different elevations = different norms of reactions
- modern maize grows better with fertiliser but worse without than older varieties
how is narrow-sense heritability calculated?
H^2 = V(A) / V(P) = V(A) / V(G) + V(E) + V(GE)
what is reflected by narrow-sense heritability?
narrow-sense heritability reflects the fact that heritability must be subdivided into:
- additive variance, V(A) - eg. one allele means one extra inch
- dominant variance, V(D) - eg. sometimes a ‘plus’ will be dominant
- interaction variance, V(I) - the effects of one gene may be affected by those of another
what is implied by a highly additive variance?
rapid response to selection;
this has NEVER been measured for any human character
what is meant by ‘correlation’?
the interdependence of variable quantities eg. the measurement of the association between height and weight
what is signified by the correlation coefficient?
r = 0 no correlatoin r = 1/2 intermediate correlation r = 1 perfect linear correlation r = -1 perfect linear inverse correlation -1 <= +1
how can homozygosity be attained in a line?
through inbreeding
which scientist measured correlation between relatives and what was the result?
Francis Galton;
there is greater similarity between members of the same family
how can it be determined whether or not the variance of a character has a genetic basis?
- breed from individuals with an extreme value of the character
- if no response to artificial selection, variation probably has no genetic basis
eg. John Maynard Smith tried to breed a line of flies in which one crossed left wing over right, and another in which the opposite was the case; no response = zero heritability
what is indicated by the rapid domestication of the Silver Fox by artificial selection?
there must be some genetic variation for such characters in the base stock
what is a selection response?
difference in the mean value of the character in the offspring of the selected parents compared to that of the parents themselves
what is a selection differential?
the extent to which the selected parents differ from the population mean
how is heritability related to selection?
H^2 = selection response / selection differential
what is indicated by the comparison of monozygotic (MZ) and dizygotic (DZ) twins?
- DZ twins are no more related than siblings but share the same environment
- MZ twins are genetically identical and share the same environment
- any great similarity between MZs when compared to DZs might indicate a character under the control of a gene
what is the problem with comparing MZ and DZ twins?
- MZ twins share an environment to a greater extent than do DZ twins
- MZ twins often emulate one another in their behaviour
who developed the concordance method for MZ/DZ twins?
Francis Galton
for which condition was there found to be considerable concordance? is there any problem with this conclusion?
schizophrenia;
but being an identical twin may exert stresses so that twins may have eg. low birth weight, high tendency for mental illness for unfavourable environmental reasons, often placental
why are DZ twins often more genetically similar than expected?
many twins undergo blood transfusion from their DZ pair during pregnancy or even partly fused as a chimera so that they do not recognise their twin’s tissue as foreign after birth
what leads to variation in MZ twins?
- resemblance/otherwise can be changed by the environment
- there are massive differences in time when twins split, affecting the final phenotype
when do mirror-image twins split?
after the development of the positional axis of the embryo
what are dichorionic and monochorionic MZ twins?
dichorionic = separate placentas
monochorionic = share the same placenta
dichorionic twins survive much better than do monochorionic twins;
a later split increases the likelihood of monochorionic MZ twins (and of them being conjoined)
what can arise as a result of monochorionic twins?
- twins may develop poorly since they are starved of blood supply and may also be born earlier ie. similarity due to prenatal environmental reasons rather than genetic ones
- twin to twin transfusion may occur, in which one twin takes blood from the other
- donor = anaemic and underweight; recipient = overweight with heart problems
what is an example of an epigenetic effect on twins?
eg. X chromosome inactivation
- in female twins, different proportions od paternal/maternal X chromosomes may be inactivated
- in one set of MZ twins, one twin was born with Duchenne muscular dystrophy, a sex-linked recessive disease
- would not expect either twin to contract disease
- twins were heterozygotes; the maternal X was inactivated in one twin (no effect) and the paternal in the other (leading to the particular condition)
when a plant heterozygote is selfed, what is the effect on the proportion of heterozygotes and on the allele frequency?
- the proportion of heterozygotes is reduced
- the allele frequency does not change
define ‘identical by descent’
used to describe a matching segment of DNA shared by two or more people that has been inherited from a recent common ancestor without any intervening recombination
define ‘homozygosity by descent’
possessing two genes at a given locus that are descended from a single source, such as may occur in inbreeding
how is F, the coefficient of inbreeding, measured?
F = ΣN (1/2)^n
where N = number of loops; n = number of ancestors in each loop
what happens to the value of F as the degree of kinship decreases?
the value of F decreases very rapidly, to be effectively outbred beyond second cousins or so
true or false: F can build up over generations
true
give an example of an effect of inbreeding
Syringomelia in King Charles spaniels - their brains are too big for their skulls, resulting in acute pain; an operation is performed to reduce the pressure
what is genetically interesting about the population of Finland?
- population of 5 million
- genetically distinct from all other European countries
- 33 recessive diseases are unique to Finland due to inbreeding
what is an example of a recessive disease unique to Finland?
vLINCL - variant late infantile neuronal ceroid lipofuscinosis
deinf ‘inbreeding depression’
when you are sad because you are inbred.
alternatively, the reduced biological fitness in a given population as a result of inbreeding
define ‘parthenogenesis’
asexual reproduction in which the embryo develops from an unfertilized egg cell
what does SCNT stand for?
somatic cell nuclear transfer
what is somatic cell nuclear transfer?
a donor nucleus from a somatic cell is implanted into an enucleated oocyte
define ‘anisogamy’
sexual reproduction involving two dissimilar gametes, differing in size and/or form
define ‘isogamy’
sexual reproduction involving gametes of similar morphology (shape and size)
what is unique about the species Drosophila bifurca?
the male fly produces sperm several times his own body length; up to 58 mm long
define ‘pseudoautosomal regions’
the pseudoautosomal regions, PAR1, PAR2, and PAR3, are homologous sequences of nucleotides on the X and Y chromosomes, allowing recombination during meiosis; genes in this region are not inherited in a strictly sex-linked fashion
where is PAR1 located?
at the terminal region of the short arms
where is PAR2 located?
at the tips of the long arms
how has the Y chromosome changed?
- lost thousands of genes and gained only a few in the process of decay
- much reshuffling, reduction, import of genes from elsewhere (most of which rust away)
what is the Y chromosome comprised of?
- around 80 functional genes
- a quarter of the chromosomes is made up of huge palindromes
describe the palindromes found on the Y chromosome
- eight massive palindromes
- made up of 3 million bases
- 99.97% identical in the mirror image
- many functional genes sit in double copy inside these - perhaps an unusual form of mutation repair?
what is SRY?
sex-determining region Y
- encodes DNA-binding protein (SRY protein)
- mutations lead to sex-related disorders
- may have arisen from gene duplications of X-chromosome-bound gene Sox3
- role in testes development
what is unique about the sex chrosomomes of the platypus?
the platypus has 5Xs and 5Ys, which form a chain during meiosis
what information is only passed through the female line?
that contained in the cytoplasm and in the mitochondria
give an example of an experiment that demonstrates that genetic information is stored in the cytoplasm
variegated patterns in Mirabilis jalapa - the phenotype of the progeny is that of the mother and the father’s phenotype has no effect
which scientist studied Miribalis jalapa for patterns of cytoplasmic inheritance?
Carl Correns
what did Carl Correns propose?
that the proposed gene for variegated patterns in Mirabilis jalapa was in the cytoplasm and hence passed on through matrilineal inheritance
what was the phenotype of progeny of variegated females of the species Mirabilis jalapa?
offspring were green/white/variegated depending on what part of the egg cytoplasm they had received; there is a segregation of cytoplasmic determinants during the development of the plant
give an example of a maternally inherited character
- the ‘poky’ mutant of Neurospora fungus has slow growth and small colonies
- gene in the mitochondria
- mitochondrion is the site of the cell’s energy metabolism and needed for growth
- mutants lack cytochromes
how are patterns of mating determined in Chlamydonas (unicellular freshwater algae)?
the algae have ‘mating types’ - they can only mate with an individual not of their own mating type
what could result in the uniparental inheritance of some characters in photosynthetic organisms?
- chloroplasts are passed down from only one parents
- genes are contained in chloroplast DNA and held in the cytoplasm
which scientist studied uniparental inheritance involving genes contained in chloroplast DNA?
Ruth Sager
define ‘cytonet’
- also known as ‘heteroplasmon’
- a eukaryotic cell whose non-nucleic (cytoplasmic) genome is heterozygous
- due to mutation in which cytoplasm is passed down by both parents
how can the frequency of cytohets be increased?
by treating with UV light
what is the non-nucleic genome?
the cytoplasmic genome, comprised of that of cytoplasmic organelles, chloroplasts and mitochondria
what is the difficulty of producing a linkage map of Chlamydonas and how can this be resolved?
- cannot produce a linkage map if only one parent passes on the genome
- need two independent genomes present together
- 1% of crosses results in cytohets, which can be use to make a linkage map of the genome
what is the difficulty of producing a linkage map of Chlamydonas and how can this be resolved?
- cannot produce a linkage map if only one parent passes on the genome
- need two independent genomes present together
- 1% of crosses results in cytohets, which can be use to make a linkage map of the genome
what was the problem when trying to identify the central locus when carrying out a three-point cross on Chlamydonas?
comparing the parentals to double recombinants did not produce any consistent result - the gene map was circular
describe the DNA found in mitochondria
- closed circles of DNA
- many copies present in each cell
- carry genes for transfer RNAs, ribosomal RNAs, cytochromes and other metabolic genes
- slightly different genetic code from nuclear DNA
- no introns
give an example of how the genetic code in the mitochondria is different to that in the nucleus
some codons code for amino acids in the mitochondria but are stop codons in the nucleus
why is it thought that the mitochondrial genome has no introns?
probably due to the different evolutionary history of the mitochondria from the nuclear genome (endosymbiosis)
describe the mechanism of infection by Wolbachia
- bacteria in insects is passed down through eggs, eg. in ladybirds
- some kill all males
- female larvae eat the corpses of their brothers to fain fitness
- this helps the bacteria, which are passed down through eggs, not sperm
- infection continues
give examples of mitochondrial inheritance in humans
Leber’s hereditary optic neuropathy
- congenital degeneration of the optic nerve, leading to blindness
- due to deletion of a section of mitochondrial DNA
myoclonic epilepsy with ragged-red fibres (MERRF)
- abnormal mitochondria with crystallin inclusions
which organelle is damaged through ageing and how can this be detected?
mitochondria - drooping eyelids through muscle weakness as a subtle early sign of disease
what is the impact of the bottleneck effect on the pattern of mitochondrial diseases among siblings?
- as cells divide, the mitochondria (500-2000 per cell) will be randomly divided between the two cells
- some cells will have many damaged mitochondria and other only a few
- some children will have very severe symptoms and their siblings, scarcely any
what is the probability of a woman with mitochondrial disease having affected children?
- likely to have all children affected to some extent
- not like a recessive disease, in which there is a 1/4 chance that each child will inherit the condition
where in the body are mitochondria seldom renewed?
in the brain and heart
true or false: sex is a mechanism for reshuffling genes through recombination
true
what are the qualities of a perfect Hardy-Weinberg population?
- all genes are equally likely to copy themselves (ie. no effect on physical fitness)
- no mutation
- no immigration
- random mating
state the Hardy-Weinberg equation
p^2 + 2pq + q^2 = 1
where p = dominant allele; q = recessive allele
what is the result of the Hardy-Weinberg equilibrium?
population stability
according to HW, how do genotype and allele frequencies change?
genotype frequencies change but allele frequencies do not
what is the incidence of rare alleles in a HW population?
the incidence of rare alleles is far higher in heterozygotes than in homozygotes
what factors affect the HW equilibrium?
- small populations
- inbreeding
- selection
- mutation
- migration
define ‘genetic drift’
variation in the relative frequency of different genotypes in a small population due to the chance disappearance of particular alleles as individuals die/fail to reproduce
what is the standard deviation of a HW population?
standard deviation = SQRT(pq/N)
where N = population size
when are shifts between generations largest in a HW population?
- when pq is large (eg. p = 0.5, q = 0.5) ie. at intermediate gene frequencies
- when N is small ie. slower divergence in larger populations
true or false: in a HW population, a lost gene can be recovered
false; once a gene is gone, it is gone forever
how is the harmonic mean calculated?
= k / [1/N1 + 1/N2 + 1/N3 + … + 1/Nk]
what is the advantage of calculating the harmonic mean instead of the ‘regular’ mean?
it shows the importance of bottlenecks on the population (which may be unknown/unknowable due to how long ago they occurred)
which genetic effects are demonstrated by the population of Tristan da Cunha?
- founder effect
- several secondary bottlenecks
- highest incidence in the world of retinoblastoma
- very high frequency of asthma
- due to genetic change without natural selection
what is a ‘bottleneck’?
a sharp reduction in population size due to environmental effects
what is the founder effect?
loss of genetic variation that occurs when a new population is established by a very small number of individuals from a larger population
which condition has a high incidence in Pingelap?
achromatopsia (colourblindness)
why is it that cheetahs can accept skin transplants from one another?
there is almost no genetic variation in cheetahs, possibly due to a population bottleneck
what is the effective population size?
the number of individuals in a population that contribute offspring in the next generation
why do bottleneck populations lead to inbreeding and what is the effect of this?
- small populations with no free choice of mates
- reduces the incidence of heterozygotes - homozygotes by descent
give an example of the high incidence of a disease due to the founder effect
high incidence of Ellis-van Creveld in the Amish population
define ‘genetic admixture’
a genetic admixture occurs when individuals from two or more previously separated populations begin interbreeding as a result of migration, resulting in the introduction of new genetic lineages into a population
define ‘genetic swamping’
the process that occurs two genetically isolated populations come into contact and the genes from a larger population dominate over the genes in the small population, reducing its genetic diversity
what is the effect of migration on gene frequencies
migration homogenises gene frequencies over time; if sufficient interbreeding, two populations will become the same, but can take a long time for recombination to break up blocks of linked genes
explain how markers along the genome can be used to assess the risk of hypertension for an individual with both European and African origins
- African-Americans have high levels of hypertension
- if sections of chromosome 6 or chromosome 21 is of African origins, higher risk
- an increased risk hints at the location of the gene responsible
what is assortative mating?
a non-random mating pattern in which individuals with similar genotypes and/or phenotypes mate with one another more frequently than would be expected under a random mating pattern
give of an example of positive assortative mating
sheep mate with sheep similar to themselves or that look like their mothers
what is the effect of negative assortative mating?
an increase in the number of heterozygotes over time
how may negative assortative mating have arisen?
perhaps it evolved as an anti-inbreeding mechanism, since inbreeding can expose hidden recessives
what are the chances of a child of unrelated parents surviving its first year? how does this change if the child’s parents are cousins?
- the child of unrelated parents is 98% likely to survive first year
- the figure drops to 96% for the child of cousins
- this represents a doubling of the mortality rate due to inbreeding
give an example of a trait for which there is random mating and of one for which mating is generally non-random in the human population
random mating for eg. blood groups
non-random mating for eg. skin colour
how do chimpanzees reduce the chances of inbreeding?
- behavioural mechanism to reduce excess homozygosity in offspring
- young males are driven out at puberty
- this reduces the chances of them mating with their sisters
how does sex avoid excess homozygosity in offspring?
- mechanism of self-incompatibility
- one genotype (male) can only mate with a different one (female)
why are many hermaphroditic plants self-sterile?
to avoid inbreeding by self-fertilisation
how do hermaphroditic plants avoid inbreeding?
- they are self-sterile
- if different individuals are two closely related, fertilisation does not occur
- this is enforced outbreeding to prevent the loss of genetic diversity
explain the mechanism of forced outbreeding in hermaphroditic plants
- depends on a system of self-incompatibility
- often involves many alleles at a locus
- if pollen and egg carry the same one, fertilisation fails
- pollen lands on the style and must grow a pollen tube to reach the egg
- pollen is haploid; the style tissue is diploid
- eg. a x ab fails; b x ab fails; c x ab succeeds
- this system requires at least three alleles
what is the effect of the forced outbreeding mechanism on a new allele
- any new allele is initially at a great advantage, since no plant will carry it
- advantage decreases as the allele becomes more common over generations (identity by descent)
define ‘frequency-dependent selection’
frequency-dependent selection is the term given to an evolutionary process where the fitness of a phenotype depends on its frequency relative to other phenotypes in a given population
what is the ‘Bruce effect’?
- female mice from one inbred line prefer males from another
- females even prefer to lie in bedding soaked with the urine of a different male
- if a pregnant female mated to a male from her own line is exposed to a new male from a different line, she reabsorbs her foetuses in order to mate with the new male
- mice can tell the kinship of potential partners by smell, particularly of urine
- mate choice mechanism is similar to the ‘self-not-self’ recognition in the immune system, but instructs to accept (not reject) a genetically different individual
what is an inbred line?
- homozygous at all loci
- different lines are fixed from different alleles
what is a major histocompatibility complex?
a set of cell surface molecules which control a major part of the immune system in vertebrates
how does the immune system relate to inbreeding?
- perhaps the immune system developed in part as a mechanism to prevent inbreeding
- some women have recurrent spontaneous abortions - they may have husbands with similar histocompatibility antigens to their own
give an example of a way in which humans have attempted to minimise the effects of inbreeding
- Tay Sachs is a (recessive) nervous degenerative disorder
- high frequency (1/16) of Tay Sachs carriers in the Jewish group Dor Yeshorim
- nearly all individuals carry the same mutation
- possibly due to a population bottleneck
- use of matchmakers to prevent two carriers for the condition from marrying
- anonymous testing of individuals
- idea of Rabbi Eckstein
how many women may Ashkenazi Jews be descended from?
four
what is reflected by the selective number (S)?
S reflects the ability of genotypes to contribute to the next generation
what is the nature of the selective number (S) for a recessive lethal allele?
S is negative and absolute
explain the allele frequencies for a recessive lethal using H-W
if a is lethal, frequency a = q / (1+q) and frequency p = p / (1+q)
what is a major failure of the eugenics argument related to selection against a recessive allele
selection against a recessive allele is much slower when rare; this is reflected by a curve of disappearance for a recessive lethal allele
at what speed do dominant alleles disappear?
very quickly
how much time does it take for a new recessive/dominant allele to increase in frequency?
recessive - takes a very long time
dominant - takes a much shorter time
give an example of the rapid spread of an advantageous dominant allele
the alleles for insectiside resistance spread quickly under selection
how can the Murray collection be used to demonstrate the phenomenon of antibiotic resistance?
- the collection includes reference strains of harmful bacteria gathered between 1914 and 1950
- lept in suspended animation
- all susceptible to every single antibiotic used today
how can resistance be spread?
- infectious third parties
- plasmids
- sections of mobile DNA inserted into genetic material
give an example of a bacteria with multiple resistance
Plague bacillus in Madagasar
- resistance to ampicillin. chloramphenicol, streptomycin, spectinomycin, kanamycin, tetracycline, suphonamides
- resistance genes to all seven on a single length of mobile DNA
give an example of natural selection in humans
the ACE gene
- long version and short version
- only those with two copies of the long version have climbed Everest without oxygen
- only those with two copies of the long version are able to improve their performance with training
- short version is common in Africa
- long version is increasingly more common the further away from Africa
- short homozygotes retain salt more - an advantage in the arid, hot conditions of Africa
- then, in colder/drier regions, perhaps the long version was favoured in high stress conditions with less need for salt retention
- perhaps short homozygotes are more likely to have a high blood pressure?
on average, how many new mutations are found in each child compared to its parents?
sixty
why is genetics important in early cancer diagnosis?
a genetic change is detectable long before symptoms appear
how can the age of body parts be checked?
by calculating how much radioactive carbon is lost when those body parts are exposed to a source of rdiation
how often are various tissues replaced?
- skin cells 2 week
- red blood cells 4 months
- liver not yet reached first birthday
what is the relationship between rate of regeneration and probability of cancer?
tissues that are regenerated more often have a greater rate of division and therefore a higher incidence of cancer due to mutations as the cells divide
how did de Vries discover mutation?
he repeated Mendel’s experiments using Oenothera lamarckiana and observed sudden heritable changes between generations
who discovered mutation?
Hugo de Vries
what is Oenothera lamarckiana?
the evening primrose
what is unique about the mutation rate of Oenothera lamarckiana?
uniquely high mutation rate due to system of chromosome breakage and rejoining
true or false: mutation is the raw material for evolution
true
give an example of ow immune defences are based on somatic mutations
the very rapid mutation rate of immunoglobin genes constantly produces new variant forms of antibody ready to attack any new antigen
give an example of a disease thought to be due to mutation alone
Proteus syndrome - causes bone overgrowth by somatic mutation
(Joseph Merrick, the elephant man)
what categories of mutations are found in Drosophila?
- morphological - loss-of-function (mostly) and gain-of-function
- conditional - show gene-environment interaction
give an example of a gain-of-function mutation in Drosophila
homeotic mutations such as antennapedia or bithorax
describe how the mutations in maize can be observed
- maize endosperm (tissue surrounding the embryo - visible as corn-on-the-cob) is triploid
- every corn-cob is a family of different individual seeds
- it is therefore possible to examine many individuals quickly, since the seed colour is affected
which scientist investigation mutation in maize?
Lewis Stadler
explain the locus-specific test for recessive mutations
- corn colour locus C = coloured; c = white
- cc female x CC male
= endosperm is triploid - one allele from the male and two from the female - without mutation, every kernel is Ccc (coloured)
- any mutation from C to c is visible as a white kernel
true or false: mutation rates at different loci are the same
false
describe a direct method of detecting mutations in mice
- mice homozygous recessive for several coat-colour mutations are crossed with mice wildtype at all loci
- if there is no mutation, all offspring should be heterozygous for all loci
- any mutation is visible as a change in coat colour
what is the effect of injecting a mouse pregnant with heterozygour offspring with a mutagen?
the offspring will be born with patches of coloured hair
what are the problems with counting human mutations?
- illegitimacy
- heterogeneity
- phenocopies
what is heterogeneity?
several diseases are phenotypically similar and therefore difficult to differentiate
explain the heterogeneity of polydactyly
polydactyly is due to mutations at many different loci, but mutation at a single locus gives a very high rate and so was initially believed to be the cause
define ‘phenocopy’
an individual showing features characteristic of a genotype other than its own, but produced environmentally rather than genetically
give an example of a phenocopy condition
some gene mutations give rise to shortened limbs (phocomelia), but thalidomide gave the same phenotype
name a factor that contributes to the intrinsic stability of genes
- the size of the gene
- larger genes eg. Duchenne muscular dystophy have higher mutation rates
name a factor that contributes to the intrinsic stability of genes
- the size of the gene - larger genes eg. Duchenne muscular dystophy have higher mutation rates
- certain sequences seem to mutate eg. human fingerprint has a 1% mutation rate
give one theory as to why so many millions of gametes are made
perhaps this is a mechanism for filtering out new harmful mutations and only allowing the ‘best’ sperm or egg to ‘win’
what is the difference between proofreading and repair?
- proofreading = false segments are detected and synthesis is stopped until the incorrect segment is removed
- repair = actual reversal of damage
what is the error rate of newly synthesised DNA?
1/10^9 nucleotides, but the majority are repaired or kill the cell
which scientist discovered that ionising radiation causes mutation?
Hermann Muller
what is the relationship between the wavelength and wave penetration?
as the wavelength gets shorter, the waves become more penetrating
how do gamma and x-rays act as ionising radiation?
they produce ions by colliding which atoms, which then produce free radicals in the cell, potentially damaging the DNA
which parts of the electromagnetic spectrum act as ionising radiation?
gamma rays, x-rays and the higher ultraviolet part of the spectrum
what is ‘target theory’?
the theory that organisms have ‘targets’, the injury of which leads to injury of the entire organism
what is the implication of target theory?
- even a small increase in x-ray dosage is dangerous if given over a long enough period
- there is no safe low level of x-rays
- inevitable increase in genetic load
define ‘genetic load’
the increase in human damage resulting in the decline of the species
what are the effects of irradiating a male and immediately mating to a female versus delaying mating for a few hours?
- immediate mating - approximately linear relationship of mutation incidence with dose
- delayed mating - low doses of x-rays much less effectiv in causing mutation, even resulting in repair
how many were killed in Hiroshima from radiation sickness?
80 000
which cancers had an increased incidence in survivors of Hiroshima?
lung and thyroid
how did Chernobyl compare to Hiroshima in terms of radiation?
at Chernobyl,
- at least 10 million people exposed to radiation
- far less immediate exposure
- fewer than 60 deaths
- total predicted death toll of 4000
what is the effect of UV light?
UV light causes thymine dimers, a powerful somatic mutation
what is Xeroderma pigmentosum?
individuals lack a particular repair enzyme and UV carcinogenesis is therefore lethal
who discovered that war gases cause mutations?
Charlotte Auerbach - she knew that war gases caused radiomimetic burns and found that these caused mutation
what is mustard gas?
mustard gas is an alkylating agent
define ‘alkylating agent’
a substance that causes the replacement of hydrogen by an alkyl group
define ‘base analog’
a chemical that can substitute for a normal nucleobase in nucleic acids
give an example of a base analog
5-bromouracil (5BU)
define ‘acridine’
a dye that inserts itself into the growing popypeptide chain, causing a frameshift
how was the system of the Ames test made more similar to humans?
by adding minced-up fresh rat liver, since enzyme may metabolise otherwise harmless chemicals to convert them into mutagens
give some examples of diseases that are characterised by a failure of DNA repair
Bloom’s syndrome, Werner’s syndrome, progeria
what is the relationship between germinal mutation and age of parents?
an increased parental age increases the likelihood of any offspring having such conditions as achondroplastic dwarfism, since there is an increase in mutation rate with age
what is the age difference between fathers of haemophiliacs and the average?
fathers of haemophiliacs are 11 years older than the average age
what is the increased incidence of achondroplasia in children of fathers of age 45 compared to those of fathers of age 25?
11 x
why is the incidence of many hereditary disorders increased by the age of the father?
- only one division in the germline is meiotic
- the rest (producing spermatogonia) are mitotic
- there are more mitotic divisions between sperm and sperm in older fathers than in young ones
why is the age of the mother less of a factor when considering the incidence of many hereditary disorders?
- set of eggs made at puberty
- released at intervals
- fewer cell divisions
- smaller accumulation of mutations
how could the cell act as a cellular clock? how is this differete in cancer cells?
- every time a cell divides, part of the telomere is lost (mutation)
- once this reaches a maximum, the cell stops dividing
- cancer cells do not have this mutational reduction in telomere length
- continue to divide uncontrollably
in which gender is there more mutation and in which is there more recombination?
there is more mutation in males and more recombination in females - more crossovers and more splicing (repair)
women fix men’s screwups
which scientist noted the similarity between European languages and those of Northern India?
William Jones
what was the suggestion of William Jones regarding the similarity of different languages?
he proposed that they had evolved and formed a reconstructed tree suggesting evolution from a common ancestor; inevitable faults in transmission from generation to generation
what was the widely-held theory concerning the origin of language before the proposal of Jones?
it was previously held that language is of divine origin, given to man during the episode of the Tower of Babel
when is it thought that the first language existed?
~50 000 years ago
what is the genetic relationship between humans and chimpanzees?
- we are a much diminished species when considering bodily attributes
- we have lost hundreds of genes since our split with our common ancestor
what are the main differences between chimpanzees and humans?
chimpanzees ————— humans
hairy and strong ———- same number of hairs but reduced thickness
powerful teeth ———- reduced teeth
huge jaw musculature ———- mutation in single gene that makes myosin, resulting in smaller muscle cells throughout
chimps eat twice as much in relation to body weight ———- intestine wall half the length
must chew ———- reduced stomach; cooking
raw food only ———- will starve on raw food
more sperm, more sperm competition ———- less sexually impressive; smaller testes
penis spines ———- loss of penis spines
less evolved brains ———- enormous increase in brain size per body mass
communication ———- speech
more variation based on geographical location ———- very little geographical variation
summarise evolution in three words
descent with modification
how many HIV virus particles are transmitted per sexual encounter?
one
what is the implication of natural selection on CCL3L1?
homozygotes for the allele will survive much longer than heterozygotes, and those with no alleles will die first
how many copies of the CCL3L1 allele do chimps and other primates have compared to humans?
many more copies and so are unaffected/affected only mildly by eg. SIV
give an example of how language can serve as evolution in the mind
- the incidence of HIV has been reduced through education programmes focusing on reducing promiscuity
- HIV has been largely contained by the development of anti-viral drugs
what is verbal dyspraxia?
the inability to understand grammar (FOXP2 gene)
