Inheritance of Genes:
- The transmission of traits from one generation to the next is called inheritance, or heredity . However, children are not identical copies of their parents – reproduction therefore introduces variation .
- Parents endow the offspring with encoded information in the form of hereditary units called genes , written in the language of DNA, a polymer of four different nucleotides.
- Inherited information is passed on in the form of each gene’s specific sequence of DNA nucleotides.
- In animals and plants, reproductive cells called gametes are the vehicles that transmit genes from one generation to the next. During fertilization , male and female gametes, known as sperm and eggs , unite, passing on genes of both parents to their offspring.
- The DNA of a eukaryotic cell is packaged into chromosomes , which each consist of a single long DNA molecule, elaborately coiled in association with various proteins called histones.
- Every species has a characteristic number of chromosomes – for example, humans have 46 chromosomes in their somatic cells , all cells of the body except for gametes and their precursors.
- A gene’s specific location along the length of a chromosome is called the gene’s locus .
Asexual and Sexual Reproduction:
- Only organisms that reproduce asexually have offspring their exact genetic copies of themselves. In asexual reproduction , a single individual (like a yeast cell or an amoeba) is the sole parent and passes copies of all its genes to its offspring without the fusion of gametes, giving rise to a clone .
- Genetic differences occasionally arise in asexually reproducing organisms as a result of changes in the DNA called mutations.
- On the other hand, in sexual reproduction , two parents give rise to offspring that have unique combinations of genes inherited from the two parents. Offspring of sexual reproduction vary genetically from their siblings and both parents.
- The key to this genetic variation is the behavior of chromosomes during the sexual life cycle.
Chromosomes – Maternal/Paternal and Diploid/Haploid:
- A karyotype is a display of condensed chromosomes arranged in pairs.
- We inherit one chromosome of a pair from each parent from the fusion of gametes discussed earlier, thus the 46 chromosomes in our somatic cells (in humans) are actually two sets of 23 chromosomes, a maternal set (from our mother) and a paternal set (from our father).
- The two chromosomes of a pair – maternal and paternal – have the same length, centromere position, and staining pattern. These are called homologous chromosomes .
- The two chromosomes referred to as X and Y are an important exception. They are referred to as sex chromosomes – typically, human females have a homologous pair of X chromosomes (XX), while males have one X and one Y chromosome (XY), which are mostly nonhomologous. The other chromosomes are called autosomes .
- Any cell with two chromosomes is called diploid cell and has diploid number of chromosomes, abbreviated 2n .
- Note that the cell which has passed the S phase of interphase in which DNA has been replicated is still referred to as diploid, or 2n , since it only has two sets of information regardless of the number of chromatids, which are merely copies of the information in one set.
- Unlike somatic cells, gametes contain a single set of chromosomes (abbreviated n ) and are called haploid cells .
- Each sexually reproducing species has a characteristic diploid and haploid number, for humans 2n is 46 and n = 23, for Drosophila (fruit flies) 2n is 8 and n is 4, while for dogs, 2n is 78 and n is 39.
Sexual Life Cycles:
- The human life cycle begins when haploid sperm from the father fuses with the haploid egg from the mother. This union of gametes, culminating in the fusion of their nuclei, is called fertilization . The resulting fertilized egg, or zygote , is diploid because it contains two haploid sets of chromosomes.
- Mitosis of the zygote and its descendent cells generates all the somatic cells of the body, passing the chromosome set of the zygote to the somatic cells.
- The only cells in the human body not produced by mitosis are the gametes, which develop from specialized cells called germ cells in the gonads – ovaries in females and testes in males.
- Gamete formation involves a type of cell division called meiosis , which reduces the chromosome number from 2n to n in the gametes, counterbalancing the doubling that occurs at fertilization (which restores the diploid condition).
- Fertilization and meiosis alternate in sexual life cycles, maintaining a constant number of chromosomes in each species from one generation to the next.
- Although the alternation of meiosis and fertilization is common to all organisms that reproduce sexually, the timing of these two events in the life cycle varies, depending on the species. These variations can be grouped into three main types of life cycles:
- In humans and most other animals, gametes are the only haploid cells, and undergo no further cell division prior to fertilization. After fertilization, the diploid zygote divides by mitosis, producing a multicellular diploid organism.
- Plants and some species of algae exhibit a second type of life cycle called the alternation of generations . This type includes both diploid and haploid stages that are multicellular.
- The multicellular diploid stages called the sporophyte . Meiosis in the sporophyte produces haploid cells called spores .
- Unlike the gametes, a haploid spore doesn’t fuse with another cell. Instead, it divides mitotically, generating a multicellular haploid stage called the gametophyte .
- Cells of the gametophyte give rise to gametes by mitosis, and fusion of two haploid gametes at fertilization results in a diploid zygote which develops into the next sporophyte generation
- Therefore, the sporophyte generation preaches the gametophyte as its offspring, and the gametophyte generation produces the next sporophyte generation, as depicted below.
- Image Credit: “Alteration of Generations” by Peter Coxhead (Public Domain).
- The third type of life cycle occurs in most fungi and some protists (including some algae).
- After gametes fuse and form a diploid zygote, meiosis occurs without a multicellular diploid offspring developing.
- Meiosis produces not gametes, but haploid cells that then divide by mitosis and give rise to other unicellular descendants or a haploid multicellular adult organism. Subsequently, the haploid organism carries out further mitosis, producing the cells that develop into gametes.
- The only diploid stage found in these species is the single-celled zygote.
- All three types of sexual life cycles result in genetic variation among offspring.
- Meiosis is the type of cell division which results in gamete formation, and reduces the number of sets of chromosomes from 2n to n .
- Like mitosis, meiosis is preceded by the duplication of chromosomes. However, the single duplication is followed by two consecutive cell divisions, called meiosis I and meiosis II .
- For a single pair of homologous chromosomes and diploid germ cell, both members of the pair are duplicated, and copies sorted into four haploid daughter cells.
- Note that sister chromatids are two copies of one chromosome, closely associated via sister chromatid cohesion, while the two chromosomes of a homologous pair are individual chromosomes that were inherited from each parent with different alleles (different versions of a gene at corresponding loci).
- The stages of meiosis I and II are as follows:
- Image Credit: “Meiosis II: Figure 5” by OpenStax College, Biology (CC BY 3.0).
Crossing Over and Synapsis During Prophase I:
- After interphase, chromosomes have been duplicated and the sister chromatids are held together by proteins called cohesins .
- Early in Prophase I, the two members of a homologous pair associate loosely along their length. Each gene on one homolog is aligned precisely with the corresponding allele of that gene on the other homolog.
- The DNA of two nonsister chromatids – one maternal and one paternal – is broken by specific proteins at precisely matching points.
- The formation of a zipper like structure called the synaptonemal complex holds one homolog tightly to the other.
- During this association, called synapsis , the DNA breaks are closed so that each broken and is joined to the corresponding segment of the nonsister chromatid. Thus, a paternal chromatid is joined to a piece of maternal chromatid beyond the crossover point, and vice versa.
- These points of crossing over become visible as chiasmata after the synaptonemal complex disassembles. The multiple chiasma each help to keep the homologs attached as they move together to the metaphase I plate.
How does homologous recombination occur on a molecular level? (1) An enzyme called Spo11 introduces a double-stranded break (DSB) in one chromosome of the homologous pair. (2) The enzyme MRX resects the 5’ end of the DSB. Note that new nucleotides cannot be added to the 5’ end, they can only be added to the 3’ end. (3) Therefore, the longer 3’ overhangs invade the homologous helix, facilitated by Dmc1 and Rad51, forming a D-loop. (4) The 3’ end is extended, copying its homologous pair. (5) The 3’ end is captured by and ligated back to the original strand, forming two Holliday Junctions (HJs). (6) Depending on where the junctions are cut, non-crossover repair or crossover (such as in meiosis) can occur.
“During meiosis, homologous chromosomes are sorted into pairs, and then intimately align, before being correctly segregated, so that each gamete carries only a single copy of each chromosome. During leptotene each chromosome must find and recognize its homologue from among all the chromosomes present in the nucleus. The homologues then associate. During zygotene, a proteinaceous structure, known as the synaptonemal complex (SC), is assembled between the homologues as they align, in a process called synapsis. The SC is thought to act as a scaffold to facilitate crossovers between chromosomes.
Recombination is initiated by the formation of double strand breaks (DSBs) at leptotene, before the chromosomes have paired (Fig. 5). The DSBs allow one of the free 3’ ends to invade a homologous region on a chromosome from the other parent. This ‘strand invasion’ displaces one chromosome strand from the other parent forming a D-loop. The DSBs are repaired using homologous sequences on chromosomes from the other parent as template, and the free ends eventually ligate, leading to the formation of Holliday Junctions between the synapsed chromosomes. Each Holliday Junction can be resolved by cutting either horizontally or vertically and ligating. Horizontal cuts in both Holliday Junctions lead to non-crossover. However, if one junction is cut vertically and the other horizontally, this results in a crossover. Each crossover event forms a chiasma, which holds the homologues together after the SC is disassembled.”
Sung P, Klein H. Mechanism of homologous recombination: mediators and helicases take on regulatory functions. Nat Rev Mol Cell Biol. 2006 Oct;7(10):739-50. Epub 2006 Aug 23.
“Double-strand breaks (DSBs) can be repaired by several homologous recombination (HR)-mediated pathways, including double-strand break repair (DSBR) and synthesis-dependent strand annealing (SDSA). a) In both pathways, repair is initiated by resection of a DSB to provide 3′ single-stranded DNA (ssDNA) overhangs. Strand invasion by these 3′ ssDNA overhangs into a homologous sequence is followed by DNA synthesis at the invading end. b) After strand invasion and synthesis, the second DSB end can be captured to form an intermediate with two Holliday junctions (HJs). After gap-repair DNA synthesis and ligation, the structure is resolved at the HJs in a non-crossover (black arrow heads at both HJs) or crossover mode (green arrow heads at one HJ and black arrow heads at the other HJ). c) Alternatively, the reaction can proceed to SDSA by strand displacement, annealing of the extended single-strand end to the ssDNA on the other break end, followed by gap-filling DNA synthesis and ligation. The repair product from SDSA is always non-crossover.”
Further Reading: Cromie GA, Hyppa RW, Taylor AF, Zakharyevich K, Hunter N, Smith GR. Single Holliday Junctions Are Intermediates of Meiotic Recombination. Cell. 2006 Dec 15; 127(6): 1167–1178. doi: 10.1016/j.cell.2006.09.050 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803030/
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