Biochem: Evolution and Bioinformatics

homologous proteins …

proteins derived from a common ancestor

the two classes of homologs:

orthologs and paralogs

orthologs are …

proteins with similar or identical function in two different species 

paralogs are …

proteins with similar or identical function in the same organism

orthologs arise from …

speciation

paralogs arise from …

gene duplication

homologous proteins (especially orthologs) are expected to share …

similar 3D structure, biological function, and enzymatic mechanism

similarity between 2 proteins can be determined by …

their 3D structure and their aa sequence

Angiogenin is _____ identical to RNAse

35%

the general rule for proteins in terms of meaningfulness …

>25% = meaningful

<15% is not meaningful 

any 2 alpha helices are probably ____ identical

20%

if you want to know whether the alpha chain hemoglobin is homologous with the structure of human myoglobin, you would …

look at the 3D structure

since myoglobin is bigger than hemoglobin, when comparing the two, it’s necessary to …

introduce a “gap” in Hb to represent the part of the Mb structure missing in the alpha chain of Hb

introducing a “gap” give us …

38 identical resides (or 25.9% identity)

every “gap” decreases the …

score of the alignment

if the alignment is better than the scrambled matches …

the alignment is significant 

BLAST analysis is used to …

see if a protein is present in other organisms

Using a BLAST analysis allows us to …

determine the frequency with which a given amino acid can be functionally “replaced” by each of the other amino acids

identifying similar amino acids give us …

much more useful information than only comparing identical amino acids 

BLOSUM62 matrix is used for …

assigning similar aa substitutions

identity alone isn’t good enough to see …

significant homology between more-distantly related proteins

3D structure is better than aa sequence at …

predicting homology 

function of leghemoglobin:

sequester oxygen

leghemoglobin is found in the …

root nodules of LEG-uminous plants, where nitrogen fixation is carried out by symbiotic Rhizobium bacteria

leghemoglobin prevents oxygen from …

getting into the delicate apparatus while at the same time providing sufficient oxygen to the bacteria in the nodules

hexokinase is the …

first enzyme of glycolysis

TBP is a …

TATA Box binding protein

TBP has a repeated sequence of ..

30% identity over 90 residues 

convergent evolution (as it relates to proteins):

proteins of different origin with the same properties

chymotrypsin and subtilisin both …

cut peptide bonds in proteins

have a “change relay network” involving Ser-His-Asp where residues have same spatial arrangement

the fold of chymotrypsin is …

different from the fold of subtilisin, even though they share many factors like an active site and mechanism

RNA structure is …

conserved, just like protein sequence

fossil records confirm that …

mutation rates are constant over time

the length of the branch connecting a pair of proteins (in an evolutionary tree) is …

proportional to the number of aa differences between the two sequences

modern fish with jaws, scales and paired fins have …

tetrameric Hb

the ancestors of modern fish have monomeric globin and the tetramer of jawed fish …

evolved later

the fossil record indicates that the jawless fish diverged from the bony fish about …

400 M years ago

tetrameric Hb evolved …

350 M years ago

evolutionary trees show evidence of …

horizontal gene transfer

Galdieria, a red algae, picked up …

a gene it needed from bacteria, even though when comparing genomes, they seem to fit in with other eukaryotes

doing a comparison based on a certain gene that is involved with arsenic transport within Galdieria is direct evidence of …

horizontal gene transfer

Neanderthal is more closely related to _______ than it is to humans

Denisovans

H. sapiens did not descend from _________; we simply share a common ancestor with them

Neanderthals

Svante Paabo:

completed the very difficult task of sequencing the entire genomes of the European Neanderthals and the Asian Denisovans, just from fragments of bone and teeth

Neanderthal DNA is present in humans, in some capacity, suggesting that …

H. sapiens and Neanderthals must have interbred at some point after their split 570K years ago

synteny:

order of genes along a chromosome 

when comparing chromosome #2 in humans and chimps …

human chromosome #2 is much larger, whereas in chimps, they have 2 smaller chromosomes as #2

Neanderthals and Denisovans have __________

the long Chromosome 2

Chromosomes of humans and ____ do not show as much synteny 

mice

although we share most of our genes with mice …

when mapping the locations of the genes on the chromosomes, it shows just how far we are from rodents

aptamers:

polynucleotides (usually RNA) that have the ability to bind specific ligands

the ability of aptamers to bind to specific ligands is due to …

the huge variety of structures that RNA can assume

in order to find the molecule that binds to a specific ligand, you have to …

start with a large number of candidate RNAs and apply a “selection”

(Aptamers): when applying a pool of RNAs of random sequence to an ATP-affinity column …

the non-binders flow through and are discarded, while the RNAs that were bound were eluted (amplified) and repeated

eluted:

amplified under mutagenic conditions 

(Aptamer Affinity Column): after repeating the sequence …

molecules that were left were found to be related in sequence and predicted a secondary structure —> furthered confirmed by NMR