Wednesday, 23 December 2020

Structure and Organisation of Chromosomes

 During nucleotides polymerization two strands of DNA come together to form a long double helix, with millions of base pairs. But to go from this to a more complete understanding of all the chromosomes in every one of your cells is a pretty big leap.

  DNA is not just floating around the nucleus in the double helix form. DNA is typically coiled up to save space, because there is so much of it to store. DNA strands are wrapped around proteins called histones, and these DNA-histone complexes are called nucleosomes. Then, this undergoes further supercoiling until we get chromosomes of the familiar shape.

  In a human diploid cell, which is every cell in your body except for reproductive cells, there are two versions of every chromosome, one maternal and one paternal, which makes two sets of 23 chromosomes, or 46 in total. Each chromosome will duplicate through DNA replication to give two identical sister chromatids.

Homologous pair of chromosomes contains the same genes, but different alleles for that gene, one from each parent, so these are not precisely identical to one another. But each chromosome consists of two identical sister chromatids, which will be pulled apart during mitosis. So that each daughter cell can have a complete set of chromosomes.

  When Mendel spoke of genes, it was an abstract concept, as no one knew about DNA at that time. But later in the century when microscopes became powerful enough to see chromosomes and watch mitosis take place, scientists began to see that Mendel had been exactly right, and they developed the chromosome theory of inheritance.
 
They realized that the genes we learned about from Mendelian genetics are actually long stretches of DNA that code for various proteins. These genes have specific locations on specific chromosomes, and each chromosome in a homologous pair has the same gene at the same spot. This new understanding explained all of Mendel’s observations.

   In meiosis, homologous pairs of chromosomesare separated, which accounts for the law of segregation. Only one allele for a particular gene will show up in a gamete, not both. And the fact that homologous pairs are arranged only during this process accounts for the law of independent assortment, because if two genes are located on two different chromosomes, the combination of alleles for those two genes that ends up in a particular gamete will be totally random as well.

  So before DNA structure was fully understood, we knew that chromosomes contained genes. Now we understand, each chromosome contains hundreds or even thousands of genes. Even still, genes only comprise around one to one and a half percent of the genome. So rest is, in between all the genes is noncoding DNA. This is the majority of the DNA, which doesnot code for any proteins.

However, this area still serves a varietyof functions, like
• Transcribing RNA’s other than mRNA,
• Serving as origins of replication,
• Regulating gene expression,
• Comprising centromeres as well as telomeres.
 
  Telomeres, are found at the ends of each chromosome, and they are sections of DNA where, in humans, the sequence TTAGGG is repeated hundreds of times. This is because with every round of DNA replication, the enzymes involved can’t quite copy the last couple bases, so this extra padding is present so that even after many rounds of replication, the ends haven’t shortened so much that the genetic information present within an actual gene starts to get eroded away, which would be harmful to a cell. If this does happen, it is called replicative senescence.

In some cells, an enzyme called telomerase regularly extends the telomeres, which buys a cell a little more time. Beyond telomeres, some are as of noncoding DNA are called transposons. These are sequences that can change position within a genome.

Key difference between the chromosomes of human males and females.

There is a pair of sex chromosomes present in each cell, and for a female these are both X chromosomes, with the familiar shape. But for a male, one of these is X and oneof these is a Y chromosome, which is much smaller.
  During meiosis, all egg cells get X chromosomes, since that’s all there is in the parent cells of a female, but sperm cells can end up with either an X or a Y,
since they are both present in diploid cells for the male.

A cell or zygote that inherits two X chromosomes upon fertilization will become a female, and one that gets an X and a Y will become male. These two chromosomes are partially homologous,but obviously the Y chromosome is missing genes that are present on the X chromosome, as the Y is much smaller. This means that males have only one allele for certain genes where females will have two. These are called X-linked genes, because theyare present only on the X chromosome and not the Y.
 
  In such a case, if the singular allele is recessive, a male will express the recessive phenotype, as there is no dominant allele present to override this. There are a number of disorders that are attributed to X-linked genes, such as color-blindness and hemophilia.

We should also note that females, with two X chromosomes, typically have one of these largely inactivated in each cell, and the inactive one is chosen at random, so some cells have an active X chromosome that camefrom the mother, and some from the father.

This results in phenotypes like two colors of fur on female cats, because some of the cells have an X chromosome active with anallele for one color of fur, and other cells have the other X chromosome active, which has the other allele, and corresponds to a different color. A replicated chromosome consisting of two sister chromatids, is made of looped domains wrapped around a scaffold. These looped domains can be unwound to reveala fiber of nucleosomes, which result when DNA wraps around histones to form tiny beads. 

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