no similarity vs no homology If two (complex) sequences show significant similarity in their primary sequence, they have shared ancestry, and probably similar function. THE REVERSE IS NOT TRUE: PROTEINS WITH THE SAME OR SIMILAR FUNCTION DO NOT ALWAYS SHOW SIGNIFICANT SEQUENCE SIMILARITY for one of two reasons: a) they evolved independently (e.g. different types of nucleotide binding sites); or b) they underwent so many substitution events that there is no readily detectable similarity remaining. Corollary: PROTEINS WITH SHARED ANCESTRY DO NOT ALWAYS SHOW SIGNIFICANT SIMILARITY.

Simplify the display  Show only alpha carbons  Turn off show backbone oxygen  Color secondary structure  Turn 3 D display on

betaTB and betaE with RMS coloring compared to betaDP  Magic fit -> fit molecules -> RMS coloring  RED: Long wavelength = long distance between structures  BLUE: Short wavelength = short distance between structures  If you need to switch the reference layer, you can do so in the SwissModel menu

The 3 point alignment tool  If you want to compare the structure of very dissimilar proteins that use a similar substrate, sometimes it helps to align the substrates.  This can be done through the 3 point alignment tool.

The central dogma Why might this be wrong or incomplete

Replication lagging and leading strand - strand bias

Transcription

 Prokaryotes  Eukaryotes

RNA processing  Intron types  RNA can be the catalyst Simple illustration of a pre-mRNA, with introns (top). After the introns have been removed via splicing, the mature mRNA sequence is ready for translation (bottom).

RNA enzymes:

Ribosome

Self-splicing introns

Group II intron

The RNA world concept  What arguments support an “RNA world” preceding a two biopolymer world?

Cenancestor (aka MRCA or LUCA) as placed by ancient duplicated genes (ATPases, Signal recognition particles, EF) The “Root” strictly bifurcating no reticulation only extant lineages based on a single molecular phylogeny branch length is not proportional to time The Tree of Life according to SSU ribosomal RNA (+) PHYLOGENY: from Greek phylon, race or class, and -geneia, born. “the origin and evolution of a set of organisms, usually of a species” (Wikipedia);

Tree, Web, or Coral of Life? Charles Darwin Photo by J. Cameron, 1869 Page B26 from Charles Darwin’s ( ) notebook (1837) “The tree of life should perhaps be called the coral of life, base of branches dead”

Which Type of Coral?

Darwin’s coral was a red algae (Bossea orbignyana) From Florian Maderspacher: “The captivating coral--the origins of early evolutionary imagery.” Curr Biol 16: R The captivating coral. According to the ideas of Horst Bredekamp, parts of the diagram in Darwin's origin of species (centre) more or less directly reflect the branching properties of a specimen Darwin collected himself.

The Coral of Life (Darwin)

Gene Transfer and Phylogenetic Reconstruction: Friends or Foes? Popular view  Gene transfer is a disruptive force in phylogenetic reconstruction. New view  Events of ancient gene transfer are valuable tools for reconstructing organismal phylogeny.

1. Any ancient gene transfer to the ancestor of a major lineage implicitly marks the recipient and descendents as a natural group. 2. The donor must exist at the same time or earlier than the recipient. Ancient HGTs

Gene “ping-pong” between different lineages can be used to build correlations between different parts of the tree/net of life. Presence of a transferred gene is a shared derived character that can be useful in systematics.