Saturday, 27 July 2013
Genome- The Code of Us
The genome is like a page of printed music, the page is a material object but the notes and scores are coherent with realisations in space and time; in a range of ways but in a range of limited ways. Our species is one amongst many and the code of us is what the genome contains; in the beginning was the word and the word was with our genes. The typical inventory of a human genome contains both moderately repetitive and highly repetitive DNA, namely functional classes of dispersed gene families (e.g. globin, actin), tandem gene family arrays (ribosome, histone and tRNA genes). It also contains the highly repetitive minisatellites (most of the heterochromatin around centromeres), telomeres and microsatellites (distributed throughout genome). Components with unknown function or vestigiality include the long and short interspersed elements (LINEs and SINEs) as well as pseudogenes. Many of the variations between individual genomes come in the form of single-nucleotide polymorphisms (SNPs), which are single-base differences; such SNPs in recombination-poor areas such as mtDNA and Y-chromosomes tend to remain together and define a person's individual haplotype (co-inherited genetic polymorphisms). Another important haplotype is the major histocompatibility complex (MHC); in the genome MHC proteins, which are clustered on chromosome 6, are especially polymorphic and help the host to identify foreign proteins and activate innate immunity by T-cell receptors. Dynamic components of the genome (those that can move around in it) are found in all organisms: retrotransposons (class I) copy themselves through an RNA intermediary and comprise many degenerate retroviruses, transposons (class II) encode transposase which cuts and pastes it some place else in the sequence, they contain upside-down repeats at their ends which are targets of the cut and paste process. Interestingly, retroviruses (which use reverse transcriptase) is susceptible to errors in the transcription process and thus inactivates them and integrates them into the host genome, such endogenous retroviral insertions (ERVs) are specific to species and if two species share the same ERVs in identical mutation points, it is evidence of common ancestry. Other examples of shared mutations includes the pseudogene responsible for the silencing of the enzyme L-gulonolactone oxidase; which is involved in vitamin C synthesis, such is evidence for common descent between humans and other simians. Repeated copying of sections of the genome can produce large volumes of homologues such as the super-family of G-protein-coupled receptors (GPCRs), 700 of which are in the human genome. But what makes us different to chimpanzees is more subtle, differing in our sequences by around 13 Mb, we diverge in terms of transcription factors like FOXP2 (responsible for language). But this is a classic paradox, given that yeast can survive a sacrifice of 80% of their genes while the 13Mb (4%) variation between humans and chimpanzees cause profound change in the phenotype. Let's examine the progress made in genome sequencing: Sanger's method uses DNA polymerase to create a new strand of DNA; the polymerase needs a supply of nucleotide triphosphates and the enzyme adds to the growing primer strand, this leads to the polymerase chain reaction (PCR) which amplifies small quantities of DNA. The whole-genome shotgun approach involves sequencing random fragments of the DNA and putting them back in the right order again, such overcomes the tedious nature of making a map as the basis for the assembly of partial sequences.