NaimExplain

Somatic recombination in the IGH gene of B cells is used to make cell-specific immunoglobulin heavy chains. The human IGH gene has multiple but slightly different repeats for each of four types of gene segments: V (first part of variable region), D (diversity region), J (joining region), and C (constant region; each of the C gene segments has a coding sequence split by introns). An immunoglobulin heavy chain is made by bringing together coding sequences from one each of these four types of segments (shown here as filled boxes). Two sequential somatic recombinations produce first D-J joining, then a mature, functional VDJ coding sequence unit, which is effectively a large novel exon. Another type of somatic recombination (known as class switching can change the position of C gene segments so that other C gene segments can be used instead of Cμ to give alternative classes of immunoglobulin.

General effect of a selective sweep for an advantageous DNA variant. (A) Heterozygosity profile before selection. Imagine that an advantageous DNA variant has just occurred on a founder chromosome 22. We might expect significant heterozygosity, as shown by the six representative chromosome 22s. (B) Heterozygosity profile after positive selection over many generations. Vertical transmission of the founder chromosome 22, recombination, and continued positive selection for the advantageous variant will result in an increased frequency of the advantageous DNA variant plus closely linked DNA variants, causing reduced heterozygosity for that chromosome segment.

Human-specific amino acids in the FOXP2 protein: an example of positive selection fostering language acquisition? The FOXP2 gene has been very highly conserved: the chimpanzee, gorilla, and macaque have the same FOXP2 protein sequence, and the substitutions shown refer to changes from that common sequence. Thus, the mouse protein is identical except for one conservative substitution. Given the extraordinary level of evolutionary conservation, it is very unusual to find two amino acid substitutions in the short evolutionary branch leading to modern humans and Neanderthals. These changes affect specifically cortico-striatal circuits involved in developing motor and cognitive skills

Example of abnormal phenotypes in DNA-repair disorders. 1. Extensive skin cancer in xeroderma pigmentosum. 2. Accelerated aging in Werner syndrome. 3. Characteristic quadriradial and triradial chromosome formations in Fanconi anemia cells after treatment with mitomycin C.

Describe mitochondrial DNA (mtDNA) replication? Instead of two copies, mitochondrial DNA (mtDNA) replication is stochastic. When a mitochondrion increases in mass in preparation for cell division, the overall amount of mitochondrial DNA increases in proportion, but individual mtDNAs replicate unequally. Variants of mtDNA can arise through mutation so that a person can inherit a mixed population of mtDNAs (heteroplasmy). Unequal replication of pathogenic and nonpathogenic mtDNA variants can have important consequences.

Describe the complete cell cycle including when the single strand becomes two strands and what role cohesins and centromere play throughout? The cell cycle consists of four major phases (in the additional G0 phase a cell exits from the cell cycle and remains suspended in a stationary phase that resembles G1). the two double helices are held tightly together along their lengths by binding proteins called cohesins, and the chromosome now consists of two sister chromatids each having a DNA double helix. The sister chromatids becomes more obvious in late S phase when most of the cohesins are removed except for some at the centromere, which continue to hold the two sister chromatids together. The sister chromatids finally separate in M phase to form two independent daughter cells.

Explain human telomere structure? Human telomere structure. A tandem array of roughly 2000 copies of the hexanucleotide TTAGGG is followed by a single stranded protrusion (by the G-rich strand). The single-stranded terminus can loop back and invade the double-stranded region by base pairing with the complementary C-rich strand.