3.3 meiosis

Question 1

what is meiosis?

Answer 1

• the process by which sex cells (gametes) are made in the reproductive organs
• reduction division of a diploid germline cell into four genetically distinct haploid nuclei
• 2 cellular divisions:
  1. meiosis I: 1st meiotic division separates pairs of homologous chromosomes to halve the chromosome number (diploid → haploid)
  2. meiosis II: 2nd meiotic division separates sister chromatids (created by replication of DNA during interphase)

Question 2

outline the differences between mitosis and meiosis

Answer 2

MITOSIS:

• 1 division
• diploid cells produced
• no crossing-over in prophase
• no chiasmata formation
• homologous pairs do not associate and line up at equator in metaphase
• sister chromatids separate in anaphase

MEIOSIS

• 2 divisions
• haploid gametes produced
• crossing-over in prophase I
• chiasmata form
• homologous pairs associate as bivalents and line up at equator in metaphase I
• homologous pairs separate in anaphase I and sister chromatids separate in anaphase II

Question 3

what do all chromosomes in meiosis consist of?

Answer 3

• 2 sister chromatids
• meiosis preceded by interphase, during which dna is replicated (in the S phase) to produce 2 genetically identical copies
• 2 identical dna molecules identified as sister chromatids, held together by a single centromere
• sister chromatids separated during meiosis II, following separation of homologous chromosomes in meiosis I

Question 4

what is the purpose of the halving of the chromosome number?

Answer 4

• halving of chromosome number allows sexual life cycle with fusion of gametes
• fertilisation essential in sexual reproduction, as 2 gametes will fuse to form a zygote that will develop into an organism
• key advantage of sexual reproduction is genetic variation as 2 different gametes with different genetic makeup is involved
• for fertilisation to occur to form a normal diploid zygote, each gamete must be haploid, meaning that each will have half the normal number of chromosomes and half the amount of dna
• halving is not a random halving of chromosomal number, but rather that no homologous pairs are present in the gamete
• if chromosome number was not halved in gametes, total chromosome numbers would double each generation (polyploidy)

Question 5

outline the overall process of meiosis, including meiosis I and meiosis II

Answer 5

• meiosis consists of 2 divisions, both of which follow the same stages as mitosis (prophase, metaphase, anaphase, telophase)
• preceded by interphase, in which DNA is replicated to produce chromosomes consisting of two sister chromatids
• 2nd growth phase called interkinesis may occur between meiosis I and II, however no DNA replication occurs

MEIOSIS I

• 1st meiotic division is a reduction division (diploid → haploid) in which homologous chromosomes are separated
  1. P-I: chromosomes condense, nuclear membrane dissolves, homologous chromosomes form bivalents, crossing over occurs
  2. M-I: spindle fibres from opposing centrosomes connect to bivalents (at centromeres) and align them along the middle of the cell
  3. A-I: spindle fibres contract and split the bivalent, homologous chromosomes move to opposite poles of the cell
  4. T-I: chromosomes decondense, nuclear membrane may reform, cell divides (cytokinesis) to form 2 haploid daughter cells

MEIOSIS II

• • NO DNA REPLICATION OCCURS PRIOR TO START OF P-II
• 2nd division separates sister chromatids (chromatids may not be identical due to crossing over in prophase I)
  1. P-II: chromosomes condense, nuclear membrane dissolves, centrosomes move to opposite poles (perpendicular to poles in P-I)
  2. M-II: spindle fibres from opposing centrosomes attach to chromosomes (at centromere) and align them along the cell equator
  3. A-II: spindle fibres contract and separate the sister chromatids, chromatids (now called chromosomes) move to opposite poles
  4. T-II: Chromosomes decondense, nuclear membrane reforms, cells divide (cytokinesis) to form 4 haploid daughter cells
• final outcome of meiosis is production of 4 haploid daughter cells
• cells may all be genetically distinct if crossing over occurs in prophase I (causes recombination of sister chromatids)

Question 6

what is crossing over?

Answer 6

• in prophase I, homologous chromosomes undergo process called synapsis, where they pair up to form bivalent (or tetrad)
• homologous chromosomes held together at points called chiasmata (singular: chiasma)
• crossing over of genetic material between non-sister chromatids can occur at these chiasmata
• as a result of this exchange of genetic material, new gene combinations formed on chromatids (recombination)
• once chiasmata are formed, homologous chromosomes condense as bivalents and then separated in meiosis
• if crossing over occurs then all 4 haploid daughter cells will be genetically distinct (sister chromatids are no longer identical)
• crossing over btwn non-sister chromatids results in recombination of alleles

Question 7

what is random assortment?

Answer 7

• during metaphase I, homologous chromosomes line up at equator as bivalents in 1 of 2 arrangements:
  1. maternal copy left / paternal copy right
  OR
  2. paternal copy left / maternal copy right
• orientation of pairs of homologous chromosomes is random, as is subsequent assortment of chromosomes into gametes
• final gametes differ depending on whether they got the maternal or paternal copy of a chromosome following anaphase I
• as this random assortment occurs for each homologous pair, the number of possible gamete combinations are dependent on the number of homologous pairs
• gamete combinations = 2^n (where n represents the haploid number)
• known as independent assortment as each pair of homologous chromosomes assorts (gets distributed) independently of other chromosomes

Question 8

how is genetic variation achieved in organisms?

Answer 8

• advantage of meiotic division and sexual reproduction is that it promotes genetic variation in offspring
• 3 main sources of genetic variation arising from sexual reproduction are:
  1. crossing over (in prophase I)
  2. random assortment of chromosomes (in metaphase I)
  3. random fusion of gametes from different parents

1. CROSSING OVER
   - involves exchange of segments of dna between homologous chromosomes during prophase I
   - exchange of genetic material occurs between non-sister chromatids at points called chiasmata
   - as consequence of this recombination, all 4 chromatids that comprise the bivalent will be genetically different
   - chromatids that consist of a combination of DNA derived from both homologous chromosomes are called recombinants
   - offspring with recombinant chromosomes will have unique gene combinations that are not present in either parent
2. RANDOM ORIENTATION / ASSORTMENT
   - when homologous chromosomes line up in metaphase I, their orientation towards opposing poles is random
   - orientation of each bivalent occurs independently, meaning different combinations of maternal / paternal chromosomes can be inherited when bivalents separate in anaphase I
   - total number of combinations that can occur in gametes is 2n: where n = haploid number of chromosomes
   - humans have 46 chromosomes (n = 23) and thus can produce 8,388,608 different gametes (223) by random orientation
   - if crossing over also occurs, number of different gamete combinations becomes immeasurable
3. RANDOM FERTILISATION
   - fusion of 2 haploid gametes results in the formation of a diploid zygote
   - zygote can then divide by mitosis and differentiate to form a developing embryo
   - meiosis results in genetically distinct gametes; random fertilisation by egg and sperm will always generate different zygotes
   - identical twins are formed after fertilisation, by the complete fission of the zygote into 2 separate cell masses

Question 9

what is non-disjunction?

Answer 9

• refers to chromosomes failing to separate correctly, resulting in gametes with 1 extra, or 1 missing, chromosome (aneuploidy)
• failure of chromosomes to separate may occur via:
  1. failure of homologues to separate in anaphase I (resulting in 4 affected daughter cells)
  2. failure of sister chromatids to separate in anaphase II (resulting in only 2 daughter cells being affected)
• if zygote is formed from a gamete that has experienced a non-disjunction event, resulting offspring will have extra or missing chromosomes in every cell

Question 10

how does down syndrome come about?

Answer 10

• individuals with down syndrome have three copies of chromosome 21 (trisomy 21)
• 1 of parental gametes had 2 copies of chromosome 21 as a result of non-disjunction
• other parental gamete was normal and had a single copy of chromosome 21
• when the 2 gametes fused during fertilisation, the resulting zygote had 3 copies of chromosome 21

Question 11

what may increase the chances of non-disjunction (esp regarding that for down syndrome)?

Answer 11

• studies show that chances of non-disjunction increase as age of parents increase
• particularly strong correlation between maternal age and occurrence of non-disjunction events
• due to developing oocytes (cell in ovary which may undergo meiosis to form ovum) being arrested in prophase I until ovulation as part of process of oogenesis
• other studies also suggest that:
• risk of chromosomal abnormalities in offspring increase significantly after a maternal age of 30
• higher incidence of chromosomal errors in offspring as a result of non-disjunction in meiosis I
• mean maternal age is increasing, leading to increase in the number of down syndrome offspring

Question 12

what is karyotyping?

Answer 12

• process by which chromosomes are organised and visualised for inspection
• typically used to determine gender of unborn child and test for chromosomal abnormalities
• cells harvested from foetus before being chemically induced to undertake cell division (so chromosomes are visible –> prophase)
• stage during which mitosis is arrested will determine whether chromosomes appear with sister chromatids
• finally, chromosomes stained and photographed, before being organised according to structure
• visual profile generated is called a karyogram

Question 13

what are the different ways cells can be obtained for karyotype analysis?

Answer 13

1. CHORIONIC VILLI SAMPLING
   - chorion: part of placenta of baby and contains many cells with villi
   - involves removing a sample of the chorionic villus cells (placental tissue) via a tube inserted through the cervix / needle inserted into uterus
   - can be done at ~11 weeks of pregnancy with a slight risk of inducing miscarriage (~1–2%)
2. AMNIOCENTESIS
   - involves extraction of small amount (20 ml) of amniotic fluid (contains fetal cells) with a needle
   - amniotic fluid contains cells from fetus, which can be used for karyotyping
   - usually conducted later than CVS (~16 weeks of pregnancy) with a slightly lower risk of miscarriage (~0.5–1%)

Question 14

compare somatic and germline mutations

Answer 14

• somatic mutations – occur in a single body cell and cannot be inherited (only tissues derived from mutated cell are affected)
• germline mutations – occur in gametes and can be passed onto offspring (every cell in the entire organism will be affected); thus half of gametes carry mutation