ORIGINS OF GENETIC VARIABILITY Flashcards
WHAT IS GENETIC VARIABILITY?
presence of genetic differences
-individuals differing in genotype / many alleles
WHAT DEC/INCREASES ALLELE FREQUENCIES?
natural evolution
-the fittest will survive
DEFINE EVOLUTION.
change of alleles in a population from one generation to an other
GIVE EXAMPLES OF SOURCES OF GENETIC VARIABILITY.
-segregation of alleles in meiosis and their combination in gametes
-diffuse centromeres
-mutations
-sexual reproduction / random mating
-recombination as a result of crossing over between homologous chromosomes in meiosis
WHAT IS CLOSELY LINKED TO GENETIC VARIABILITY?
the cell cycle
DEFINE THE CELL CYCLE.
- continuously repeating process, during which a somatic cell grows, duplicates material and then divides.
- 1 cycle= time between one mitotic division to the other
DISCUSS INTERPHASE.
- G1 → growth
- S → DNA synthesis
- G2 → growth and preparation for mitosis
- G0 → “break
-microtubules extend from these centrosomes
-chromosomes threadlike structure of chromatid
-nucleolus and nuclear envelope distinct
DISCUSS MITOSIS.
-cell division (a single cell divides into two identical daughter cells)
-for growth and to repair broken down cells
DISCUSS PROPHASE AND PROMETAPHASE.
PROPHASE :
-condensation of chromosomes
-nuclear envelope breaks down
-formation of mitotic spindle
PROMETAPHASE:
-further condensation of chromosomes
-mitotic spindle attaches to kinetochores on chromosomes (found in centromeres)
DISCUSS METAPHASE.
-maximally condensed chromosomes
-chromosomes line up neatly end-to-end along the centre (equator) of the cell.
-centrioles are now at opposite poles of the cell with the mitotic spindle fibres extending from them
-checkpoint
DISCUSS ANAPHASE.
-sister chromatids are then pulled apart by the mitotic spindle which pulls one chromatid to one pole and the other chromatid to the opposite pole
DISCUSS TELOPHASE.
-at each pole of the cell a full set of chromosomes gather together.
-membrane forms around each set of chromosomes to create two new nuclei (nuclear envelope and nucleolus reform)
-single cell then pinches in the middle to form two separate daughter cells each containing a full set of chromosomes within a nucleus (cytokinesis)
WHAT ARE CHECKPOINTS?
check cell cycle for mistakes
-DNA damage in G1
-Incomplete replication in G2
-Bad attachment between the mitotic spindle and chromosomes during metaphase and anaphase
WHAT IS G0 OF INTERPHASE?
found outside the cell cycle and only highly differentiated non-dividing cells (e.g.
neurons) are found in his phase
WHAT IS THE PRINCIPLE OF MAINTAINING A CORRECT CELL CYCLE?
phosphorylation and dephosphorylation of various proteins
WHAT IS CYCLIN DEPENDENT KINASE?
kinases which regulate the passage of cells through the cycle
-dependent on cyclins
-positive and negative regulation
WHAT IS THE DIFFERENCE BETWEEN THE POSITIVE AND NEGATIVE REGULATION OF THE CELL CYCLE?
POSITIVE: allows passage of cells
cyclin E binds to CDK2 → protein synthesis of necessary proteins → next phase
NEGATIVE: does not allow passage of cells
error occurs → checkpoint releases factor p53 → stops cell cycle, DNA reparation
WHICH 2 MOLECULES ARE INVOLVED IN CARRYING ON THE CELL CYCLE?
Rb (retinoblastoma)
- tumor suppressor protein (dysfunctional in some major cancers)
- prevent excessive cell growth → prohibits cell cycle progression with mistakes
E2F
-transcription factor
-Rb binds to E2F1 → blocks transcription
WHAT ARE THE CENTROSOMAL PROTEINS AND THEIR FUNCTIONS?
A: GAMMA TUBULIN
-site of microtubule growth (mitotic spindle origin)
B: PROTEIN NuMA
-reorganizes and stabilizes mitotic spindle at -end
C: KINETOCHORE PROTEINS
- motor proteins: dynein, dynactin, kinesins
- regulatory proteins: kinases, phosphates, etc.
- Kinetochore proteins encoded by MAD and BUB genes ensure and monitor attachment of kinetochores to mitotic spindle
WHAT ARE SPINDLE CHECKPOINTS?
- control correct attachment of chromosomes and mitotic spindle
- responsible for correct transition from metaphase to anaphase
WHAT IS THE ANAPHASE PROMOTING COMPLEX?
- sister chromatids are held together through cohesion proteins
- cohesion proteins can be spliced by separase (enzyme)
- separase is inhibited by securin
- APC activates breakdown of securin → releases separase → breaks down cohesin
→ chromatids are divided
WHAT IS MEIOSIS?
cell division of gametes results in four daughter cells each with half the number of chromosomes of the parent cell
EXPLAIN PROPHASE OF MEIOSIS 1.
PROPHASE = homologous chromosomes must pair and exchange genetic information
Leptotene = two chromatids of each homolog (black, wavy lines) are associated with a chromosome core, beginning of condensation
Zygotene = chromosomal cores become parallel aligned and commence ‘zipping up’
by means of the interaction of transverse filaments with the core proteins, building of synaptonemal complex
-pairing of bivalents (pair of homologous chromosomes, held together by at least one DNA crossover)
Pachytene = - crossing-over and exchange of DNA between paired chromosomes (non-sister chromatids)
- checkpoint → meiosis only proceeds if synapsis and recombination are complete
Diplotene = separation of bivalents
-bivalents may hold together where DNA exchange is occurring → chiasmata
Diakinesis = homologous chromosomes are still connected by at least 1 chiasma, maximal chromosome condensation
-nucleolusdisappears, the nuclear envelopedisintegrates and the centrioles
move to the equator of the cell
EXPLAIN THE MECHANISM OF MEOITIC RECOMBINATION.
homologous recombination (HR) includes the formation of double stranded DNA breaks
-exonuclease cleaves nucleotides of one strand at each broken end of a DSB leaving the single-stranded tail at the 3‘ end
-these sequences now hold the ability to exchange places and during DNA exchange an unstable state forms - Holliday junction
-DNA polymerase β fills the gaps in the first molecule (in which DSBs were formed) using the other DNA molecule as a template.
Resolution of an unstable molecule (cut by topoisomerase) may result in recombination (crossing-over)
-Numerous proteins are involved in each of these processes
WHAT IS A BIVALENT?
the association of a pair of homologouschromosomesphysically held together by at least one DNA crossover.
-This physical attachment allows for the alignment and segregation of the homologouschromosomesin the first meiotic division
EXPLAIN METAPHASE, ANAPHASE AND TELOPHASE OF MEIOSIS 1.
METAPHASE = chromosome pairs on equator, centromers don´t split
ANAPHASE = separation of homologs at opposite poles (randomly in terms of parental origin)
TELOPHASE = nuclear envelope reappears, spindle disappears, nuclei form, cytokinesis
WHAT IS THE END PRODUCT OF MEIOSIS 1?
2 haploid cells
WHAT IS THE END PRODUCT OF MEIOSIS 2?
4 haploid cells
DISCUSS SPERMATOGENESIS.
-begins at puberty
-mitotically division → formation of spermatogonia
-spermatogonia grow → form primary spermatocytes
-primary spermatocytes (2n) → 2x secondary spermatocytes (n, two chromatids) → 4x spermatids (n, one chromatid) → sperm
DISCUSS OOGENESIS.
-starts during embryonic development
-mitotic division → oogonia
-oogonia grows → primary oocyte (formed during 3. month of life)
-primary oocytes continue to meiosis 1 → stay in prophase until puberty = diakinaze stage
-puberty: meiosis 1 is completed → secondary oocyte + polar body
-division stops until fertilization
WHAT ARE THE DIFFERENCES BETWEEN MALE AND FEMALE GAMETOGENESIS?
WHEN IS THE INCREASED RISK FACTOR OF NONDISJUNCTION?
M1 and ovulation
-increased risk in older women
WHAT IS NONDISJUNCTION?
the failure of homologous chromosomes or sister chromatids to separate properly during cell division
M1 = CHROMOSOMES
M2 = CHROMATIDS
NAME AND EXPLPAIN 3 ERRORS IN MEOISIS.
NONDISJUNCTION: two chromosomes dont split → move into one cell together
-one gamete with 22 chromosomes (=nullisomic = abortion unless monosomy X - Turner syndrome 45, X0)
-one gamete with 24 chromosomes (=disomic = trisomy, most famous = trisomy 21 (Down-syndrome) )
UNEQUAL CROSSING OVER: part of DNA is missing or duplicated
-inversion of chromosome
ERROR IN CENTROMERE SPLITTING: results in Isochromosome
-EG: long arm of X-chromosome remains, short arm is lost
WHAT ARE THE RESULTS OF MEIOSIS?
-reduction of diploid chromosomal number to haploid
- segregation of alleles in MI, MII (Mendel’s law)
- random assortment of homologs into gametes (according to parental origin)
- increased genetic variability through crossing over
NAME AND EXPLAIN 3 ERRORS OF MITOSIS.
DISPERMY: fertilization of an ovum by two sperm → triploidy (69 chromosomes)
CHIMAERAS: fertilization of ovum and polar body (by sperm with different gonosome)
ENDOREDUPLICATION = failure of cytokinesis leads to tetraploidy
NAME AND EXPLAIN 4 ERRORS OF MITOSIS.
DISPERMY: fertilization of an ovum by two sperm → triploidy (69 chromosomes)
NONDISJUNCTION: anaphase lag = monosomy/trisomy
- postzygotic - mosaic of 2 cell lines with different karyotype
CHIMAERAS: fertilization of ovum and polar body (by sperm with different gonosome)
ENDOREDUPLICATION = failure of cytokinesis leads to tetraploidy (92 chromosome)
WHAT IS PARTHENOGENESIS?
spontaneous division of an unfertilized egg
-karyotype = 46,XX
-result is not-life compatible organism
-leads to origin of ovarial teratoma
-Partial mole = triploid product with additional set of paternal chromosomes
-due to : dispermy or duplication of sperm chromosomes in ovum with completely destroyed female nucleus
WHAT IS GYNOGENESIS IN PARTHOGENESIS?
-ovarial teratoma (benign tumor) = division of ovum without fertilization
-duplication of chromosomes
-karyotype - 46,XX
WHAT IS ANDROGENESIS IN PARTHENOGENESIS?
hydratiform mole = complete
-pathological pregnancy / hypertrophy of trophoblast / fetal tissues not present
WHEN DOES FERTILIZATION TAKE PLACE IN MEIOSIS?
metaphase M II
EXPLAIN GAMETOGENESIS.
the development and production of the male and female germ cells required for the formation of a new individual
-meiosis via gonads
1: migration of primordial germ cells to gonads during early fetal development
2: multiplication via mitosis - referred to as gametogonia when they reach the gonadal ridge in late embryonic stage
3: from gametogonia - spermatogenesis and oogenesis can take place
WHAT DO ABNORMAL GAMETES PRODUCE WHEN THEY FERTILIZE WITH NORMAL GAMETES?
monosomy or trisomy
