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2016‐12‐15
Dec 3, 2016
Chromatin (Greek: attract dyes): the material of which the chromosomes of eukaryotes are composed (proteins & DNA).
Chromatid:
The DNA molecule of a chromosome Golden Rule: 1 double stranded DNA molecule per Chromatid
Sister Chromatid: a sister chromatid refers to either of the two identical copies (chromatids) formed by the replication of a chromosome. Sister chromatids are joined together by a centromere. Chromosome homologs, chromatids & double stranded DNA molecules
Fantasy species with only two chromosome pairs:
1N = 2 (gamete)
2N = (zygote)
4N = 8 (G2/M cell)
What is a DNA molecule? A piece of double stranded DNA (i.e. a double helix of DNA)
What is the difference between a chromosome and a chromatid? A replicated chromosome is made up of two chromatids which are joined by the centromere. The chromatids separate from each other during mitosis and is dispersed as chromatin during mitosis.
What are chromosome homologs? One chromosome of each homologous pair comes from the female (maternal chromosome) and one comes from the male (paternal chromosome). Homologous chromosomes are very similar but not identical. Each carries the same genes, but the alleles may differ. Crossing over occurs between chromosome homologues (NOT between sister chromatids).
Gene versus Allele: A gene is a stretch of a DNA that encodes a particular protein (and thereby determines a particular trait). Genes within a species may vary in nucleotide sequence and variants of a particular gene are called alleles. Thus, alleles refer to different versions of the same gene. Genotype refers to differences in alleles which in turn determines particular traits (i.e. the phenotype).
Greek: khrōma = color, soma = body  chromosome refers to a colored body (in English)
Chromosome homologs, chromatids & double stranded DNA molecules
The depicted human chromosomes (1 – 22, Y and X) represent (unreplicated)
homologous pairs. The picture is an electronic montage. Note that metaphase chromosomes exist as sister chromatids that are joined at the centromere.
Human species:
Reminder of central terms Allele ( ): different versions of the same gene. Differences in alleles determines a phenotype.
G1 cell
*
**
Homologous Chromosomes
( : different alleles) S‐phase 1N = 23 (gamete)
2N = 46 (zygote)
Cohesion:
Protein complex that joins sister chromatids
4N = 92 (G2/M cell)
Gamete: egg or sperm
(1N = haploid  haplotype)
Zygote: fertilized egg
(2N = diploid  genotype)
Kinetochore:
Protein complex at which microtubules attach to chromosomes
Chromosome numbering:
From the largest to the smallest, with the exception of sex chromosomes (Y & X)
Centromere:
Chromatid region at which kinetochores assembles during mitosis Sister chromatids in the same cell (Two “identical” DNA molecules) * *
** **
Mitosis G1 cells
Sister *
*
**
chromatids segregated to daughter cells **
*Paternal and **Maternal homologue of a given chromosome
Meiosis results in unique combinations of alleles
1. The independent assortment of 2. Exchange of homologous chromosomal the maternal and paternal homologs
regions by homologous recombination
Homolog alignment and crossing‐over during meiosis
Three sites of crossover
1 2
3 chromosome pairs  23 possible mixes
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3
Haplotypes: (1‐3‐2), (2‐4), (3‐1), (4‐2‐3)
Thus, none of the original parental haplotypes prevail after recombination
Based on Fig
21-13
Mol Biol of the Cell
Figure 21-6 Molecular Biology of the Cell
Adopted from Figure 21-10 Molecular Biology of the Cell
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2016‐12‐15
Homolog alignment and crossing‐over during meiosis
A chiasma involves cutting and ligation of paternal‐maternal chromatids Swapping of DNA strands Adopted from Figure 21‐6 Molecular Biology of the Cell
Q1: Mules result when a horse mates with a donkey. A donkey sperm cell contains 31 chromosomes and a horse egg cell contains 32, therefore the zygote would have 63. The zygote can develop normally via mitosis, but the mule offspring is sterile. Explain why mitosis is normal in cells that contain horse and donkey chromosomes, but meiosis is not. Answer: Each chromosome is on it’s own in mitosis‐chromosome replication and separation occurs independently for each horse and donkey chromosome. In meiosis, homologous chromosomes must pair in Prophase I to provide tension in the microtubule spindle. Crossing‐over is required for pairing (and attachment). Most horse and donkey chromosome are too different for homologous pairing to occur. In addition, the number of horse and donkey chromosomes are different (31/32).
bivalent
A new haplotype
(new combination of alleles on a given chromosome)
Chromosome attachment in meiosis I and meiosis II
Consider the following statement:
“Mutations of genes result in a new species”
Correct or false?
Sister chromatin kinetochores of are joined during meiosis I
Prometaphase I
MetaphaseAnaphase II: Proteolysis of the residual cohesin results in sister chromatid separation (note ) Meiosis I
Metaphase  Anaphase I: Proteolysis of cohesions along the sister chromatid arms unglues the arms. This resolves the crossovers, allowing the duplicated homologs to separate. At metaphase I, cohesins are protected by Shugoshin‐2 mediated recruitment of a phosphatase sister chromatids remain attached. Meiosis II
Note ‐ fused kinetochores
of sister chromatids
Meiosis I
Adopted from Figure 21-12
Molecular Biology of the Cell
Anaphase I
Chromosome homologues are joined by chiasmata
Sister chromatids are joined by cohesion at the centromere
‐ Note during meiosis II, but not meiosis )
Prometaphase II
Sister chromatids remains joined by cohesion
Anaphase II
Meiosis II Note ‐ attachment of sister chromatid as in mitosis. Meiosis specific cohesion has to be phosphorylated for cleavage by separase  cleavage at meiosis II, but not meiosis I
Meiosis versus mitosis
• During meiosis I, sister chromatids are linked to microtubules in the same direction (joined kinetochores until meiosis II)
• The sister chromatids of a chromosome are linked by cohesion during both mitosis and meiosis. Linkage of chromosome homologs during meiosis I is mediated by chiasma
• During anaphase I of meiosis, centromeric cohesin is protected (by Shugoshin‐2), which keep the sisters chromatids together
Q2: Is it possible to have gametes with the exact same set of chromosomes as one of the original gametes from your mother or father? Answer: There need to be crossing‐over events between the homologous chromosomes in meiosis I to keep the tension in the spindle. In addition, the paternal and maternal chromosomes are separated randomly. Thus, while an individual chromosome (haplotype) may be identical, it seems essentially impossible for the whole set to be identical to one of the original gametes.
kinetochores of sister chromatids are separated as during mitosis
Aneuploidy and human genetic disorders
Monosomy
45 chromosomes: 44 + X (Turners syndrome)
Trisomy
47 chromosomes: 46 + extra 21 (Downs syndrom)
46 + extra 18 (Edwards syndrom)
46 + extra 13 (Pataus syndrom) 44 + XXX (trippel X syndrom)
44 + XXY (Klinefelters syndrom)
44 + XYY Cause of monosomy and trisomy: Nondisjunction of a given chromosome during meiosis. In most cases this results in death of the early fetus.
Aneuploidy is in most cases caused by numerical errors in the egg. This can be attributed to differences between oogenesis and spermatogenesis in mammals.
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