(a) What is DNA transcription? Explain the process of DNA transcription in eukaryotes. (20 marks) (b) What is primary and…

(a) DNA transcription in eukaryotes (20 marks)

Transcription. Transcription is the synthesis of an RNA molecule from a DNA template by RNA polymerase. The template (antisense) strand is read 3′→5′ and the RNA grows 5′→3′, so it is complementary and antiparallel to the template and identical to the coding (sense) strand, with U in place of T. The primary product is a precursor RNA (pre-mRNA, or hnRNA).

Eukaryotic process. Transcription is in the nucleus, in chromatin, and uses three RNA polymerases: Pol I makes the large rRNAs (18S, 5.8S, 28S) in the nucleolus, Pol II makes pre-mRNA, snRNA and miRNA, and Pol III makes tRNA and 5S rRNA.

• Promoter: the core promoter has the TATA box (about −25 to −30), the initiator (Inr) and other elements, and enhancers and silencers act from a distance through the Mediator and activators. Nucleosomes are remodelled and histones acetylated to open the chromatin.
• Initiation: general transcription factors assemble on the promoter. TFIID, through its TBP, binds the TATA box, then TFIIA and TFIIB join, then Pol II with TFIIF, and then TFIIE and TFIIH, forming the pre-initiation complex. TFIIH is a helicase that melts the DNA to form the open complex, and a kinase that phosphorylates serine 5 of the C-terminal domain (CTD) of Pol II, releasing it from the promoter.
• Elongation: Pol II moves along the template with elongation factors, and phosphorylation of serine 2 of the CTD recruits the processing factors.
• Co-transcriptional processing: a 5′ cap is added early, introns are spliced out by the spliceosome (snRNPs), and the 3′ end is cleaved at the AAUAAA signal and given a poly-A tail.
• Termination: after the poly-A site is passed, an exonuclease (Xrn2/Rat1) degrades the remaining RNA and dislodges the polymerase (the torpedo model).

Contrast with prokaryotes. Bacteria have a single RNA polymerase that is directed by a sigma factor, with no capping or splicing, coupled to translation, and terminating by Rho-dependent or intrinsic (hairpin) signals.

(b) Sex determination and its hormonal regulation in humans (15 marks)

Primary sex determination is the decision of gonadal sex. It is genetic: the SRY (testis-determining factor) gene on the Y chromosome triggers SOX9 and the development of the embryonic gonad into a testis, with Sertoli and Leydig cells. In XX embryos without SRY, genes such as WNT4, RSPO1 and FOXL2 direct the gonad to become an ovary.

Secondary sex determination is the development of the internal ducts, the external genitalia and, later, the secondary sexual characters, and depends on gonadal hormones.

Hormonal regulation.

• In the male foetus, Sertoli cells secrete anti-Müllerian hormone (AMH), which makes the Müllerian ducts regress. Leydig cells secrete testosterone, first stimulated by hCG and then LH, which preserves the Wolffian ducts to form the epididymis, vas deferens and seminal vesicles.
• Testosterone is converted by 5α-reductase into dihydrotestosterone (DHT), which forms the penis, scrotum and prostate.
• In the female, no AMH is produced, so the Müllerian ducts form the fallopian tubes, uterus and upper vagina. Without testosterone the Wolffian ducts regress, and without DHT the external genitalia become the clitoris and labia.
• At puberty, GnRH, FSH and LH lead to secondary sexual characters, through testosterone in males and oestrogen in females.

Disorders show the role of hormones, such as androgen insensitivity (a 46,XY person with a female phenotype) and 5α-reductase deficiency.

(c) Speciation and the role of continental drift (15 marks)

Speciation is the evolution of new species from an ancestral population. In the biological species concept (Mayr), a species is a group of interbreeding natural populations that are reproductively isolated from others. Modes are allopatric (geographic isolation), peripatric, parapatric and sympatric (as by polyploidy). Isolating mechanisms are pre-zygotic (habitat, seasonal, behavioural, mechanical and gametic) and post-zygotic (hybrid inviability or sterility, as in the mule).

Continental drift. The break-up of Pangaea, and then of Gondwana, split once-continuous populations by vicariance, in which a barrier divides a range. The separated populations, in different environments, diverged genetically, leading to allopatric speciation over millions of years.

Evidence and examples.

• The lungfishes are found in Australia (Neoceratodus), Africa (Protopterus) and South America (Lepidosiren), a Gondwanan distribution.
• Marsupials diversified in Australia after it separated from Antarctica and became isolated, while placental mammals radiated elsewhere.
• Ratites (ostrich, rhea, emu, cassowary and kiwi) are traditionally linked to the break-up of Gondwana, though molecular studies show dispersal has also been important.
• Cichlid fishes in Africa, South America and India, and the southern beeches (Nothofagus), have a Gondwanan pattern. The lemurs of Madagascar evolved in isolation after the island separated, colonised by rafting.
• The northward drift of India and its collision with Asia later allowed the mixing of faunas and further speciation.

Continental drift thus produced large-scale vicariance, and isolated biotas evolved separately.