Question

1. Origin and Fates of new genes:
   1. Outline the processes through which genes originate, and discuss cellular functions that can (a) enhance the origination of genes, and can (b) limit the evolution of new genes,
   2. Why are retroviral gene duplications often nonfunctional, once the process is complete? (remember your genetics on gene expression)
   3. Why do gene duplications through unequal crossing often produce functional genes?
   4. What potential fates can you predict for newly-arisen genes, and what stresses might result in a change of their relative frequency?   Explain
   5. Do protein-coding genes and genes that do not code for proteins arise at differing rates?  Explain the patterns we can see, and discuss why these patterns occur.

Answer 1

a)

• The process of the “birth” of a new gene has fascinated biologists for a long time, not least because new genes are thought to contribute to the origin of adaptive evolutionary novelties and thus lineage- or species-specific phenotypic traits. A major mechanism underlying the formation of new genes is gene duplication.
• A clear example of a gene duplication conferring an adaptive response to nutrient limitation is that of the yeast hexose transporter. Undergrowth conditions with low glucose, the appearance of a new hybrid copy from two closely related paralogues, HXT6 and HXT7, increases the level of expression of the hexose transporter and, crucially, the rate of glucose transport into the cell
• Eg: the most intriguing fate of a duplicate gene, occurred in the course of the recent duplication of a pancreatic ribonuclease gene in leaf-eating monkeys. Zhang et al. demonstrated that after duplication in an African leaf-eating monkey, the protein encoded by one of the copies of the ancestral RNASE1 gene rapidly adapted at specific sites to derive nutrients from bacteria in the foregut under the influence of strong positive selection (Zhang et al. 2002). Remarkably, both the duplication and subsequent adaptation of this gene were later shown to have occurred independently in a very similar manner in an Asian leaf-eating monkey (Zhang 2006). Thus, these RNASE1 duplications represent striking cases of convergent molecular evolution.

b)

• While these retrogenes seem to have evolved a variety of functional roles (a process that may have a mechanistic basis and was likely influenced by sexual selection, see below), the functions of a disproportionately high number among them are apparently associated with the transcriptional inactivation of the sex chromosomes in the male germline during and (to a lesser extent) after meiosis.
• Thus, it now seems clear that the many mammalian retrogenes that stem from the X have been fixed during evolution and shaped by natural selection to compensate for the transcriptional silencing of their parental (often housekeeping) genes during male germline silencing of the X.

c)

• Unequal crossing over is a type of gene duplication or deletion event that deletes a sequence in one strand and replaces it with duplication from its sister chromatid in mitosis or from its homologous chromosome during meiosis. Unequal crossing over is the process most responsible for creating regional gene duplications in the genome
• When unequal crossing over creates a gene duplication, the duplicate has 4 evolutionary fates. This is due to the fact that purifying selection acting on a duplicated copy is not very strong. Now that there is a redundant copy, neutral mutations can act on the duplicate. Most commonly the neutral mutations will continue until the duplicate becomes a pseudogene. If the duplicate copy increases the dosage effect of the gene product, then the duplicate may be retained as a redundant copy. Neofunctionalization is also a possibility: the duplicated copy acquires a mutation that gives it a different function than its ancestor. If both copies acquire mutations, it is possible that a subfunctional event occurs. This happens when both of the duplicated sequences have a more specialized function than the ancestral copy.
• e)
• recent work has uncovered a number of new protein-coding genes that apparently arose from previously noncoding (and nonrepetitive) DNA sequences. Probably the first such case described in the literature is presented by the Morpheus gene family that emerged in an Old World primate ancestor (Johnson et al. 2001). Although the details regarding the emergence of the original coding sequence remain unclear, the lack of any corresponding orthologous sequences outside of Old World primates suggests a de novo origin for this gene family.