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.

What happens when DNA coils around histones/ 8 nucleosomes, and what does tightening and loosening of this coil mean? In interphase, the chromatin fiber is organized in looped domains, each containing about 50-200 kilobases of DNA, that are attached to a central scaffold of non-histone proteins. High levels of gene expression require local uncoiling of the chromatin fiber to give the 10 nm nucleosomal filaments. The diagram does not show structural RNAs that can be important in chromatin.

How does complementation in DNA differ from that of RNA? Transcription results in the synthesis of an RNA transcript in the 5'→3' direction and U replaces T.

Explain the fidelity of DNA polymerase. The classical DNA-dependent DNA polymerases are high-fidelity polymerases—they insert the correct base with high accuracy; however, we also have many non-classical DNA-dependent DNA polymerases that exhibit comparatively low fidelity of DNA replication but have roles in certain types of DNA repair and in maximizing the variability of immunoglobulins and T-cell receptors.

Explain the activities at the replication fork? The enzyme DNA helicase opens up a replication fork, where synthesis of new daughter DNA strands can begin. The overall direction of movement of the replication fork matches that of the continuous 5'→3' synthesis of one daughter DNA strand, the leading strand. Replication is semi-discontinuous because the lagging strand, which is synthesized in the opposite direction, is built up in pieces (Okazaki fragments, shown here as fragments A, B, and C) that will later be stitched together by a DNA ligase.

Description of DNA Replication? The parental DNA duplex consists of two complementary DNA strands that unwind to serve as templates for the synthesis of new complementary DNA strands. Each completed daughter DNA duplex contains one of the two parental DNA strands plus one newly synthesized DNA strand, and is structurally identical to the original parental DNA duplex.

Describe DNA and RNA bases, complementation pattern and bonds? Adenine and guanine are purines with two interlocking rings based on nitrogen and carbon atoms (numbered 1 to 9. Cytosine and thymine are pyrimidines with a single ring. Adenine, cytosine, and guanine are found in both DNA and RNA, but the fourth base is thymine in DNA and uracil in RNA (they are closely related bases—carbon atom 5 in thymine has an attached methyl group, but in uracil the methyl group is replaced by a hydrogen atom). In the A-T base pair, the adenine is connected to the thymine by two hydrogen bonds. In the G-C base pair, three hydrogen bonds link the guanine to the cytosine; a G-C base pair is therefore stronger than an A-T base pair. δ+ and δ- indicate fractional positive charges and fractional negative charges

All nucleic acid strands are polymers of a repeating unit, explain? All nucleic acid strands are polymers of a repeating unit, a nucleotide that consists of a sugar with an attached base and phosphate. The sugar-phosphate backbone is asymmetric because phosphate groups connect the carbon 5' of a sugar with the carbon 3' of the neighboring sugar. This results in asymmetric ends: a 5' end where the carbon 5' is attached to a phosphate group only, and a 3' end where the carbon 3' is attached to a hydroxyl group only