AERIAL
ANCESTORS?
Page
3:
Reliability of Molecular Phylogenies
CASE
STUDY IN MOLECULAR EVOLUTION NO. 2
Written
by Harold B. White, Sept
1995, revised February 2013
C-667
BIOCHEMICAL EVOLUTION, SPRING 2013
Proteins
and DNA sequences provide
rich sources of phylogenetic information. Although the rate at which
orthologous proteins evolve in divergent lineages is more or less
constant, the
process is not metronomic and selection can alter the rates of
evolution
significantly. Such rate changes create dilemmas such as you have
discovered in
deciding whether an ancestor of humans could fly. How big a
problem is
this?
Assignment
Part 1: Constructing a Protein Phylogeny.
Within
your group, select four
species (each representing different taxa at the Order level or above)
for
which there are many protein or gene sequences known. Each group
should
pick a different set of four organisms. Then each person should
pick a
different protein, but one that has been sequenced from each of the
taxa
selected by the group and one that has a known three dimensional
structure.
Then construct a phylogeny based on the four sequences. Thus one person
might
be investigating lactate dehydrogenase sequences from human, chicken,
alligator, and a fish while another group member in that group might be
analyzing cytochrome c from the same set of species. Please help each
other
locate sequences, run the BLAST
program (available through the National Center for Biotechnology
Information, NCBI, at <http://www.ncbi.nlm.nih.gov/BLAST/>),
construct
phylogenies, and discuss what you find in your group. If you have
trouble
selecting a protein or gene, Doolittle (19)
provides a list of 57 enzymes that have been sequenced from a variety
of
organisms. Also remember that the genomes
for many organisms are now known.
Assignment
Part 2: Protein Structure, Function, and Evolution
Phylogenetic
trees for proteins are based on linear
sequences that are compared and scored for their similarity. While this
may
show how orthologous proteins in different species are related, they
tell
little if anything about the evolutionary importance of the amino acid
substitutions that have occurred in different lineages.
A protein’s function depends on its folded
three-dimensional structure. Ideally, one would like to see how changes
in the
primary structure map onto the three-dimensional structure. By
comparing many
aligned sequences, the degree to which each residue in the sequence is
conserved can be scored and represented by a color on a
three-dimensional
structure (20,
21,
22).
Part 2 of your assignment is to take your protein and create an image
(or
images) displaying the degree to which amino acids are conserved in its
structure. A web-server to do this
is
available.
Assignment
due Friday, 8 March:
Take
your results from Parts 1 &
2 and write a report on the phylogeny and evolution of your protein.
Include
phylogenetic diagrams and a three dimensional image of your selected
protein.
Discuss its rate of evolution, utility as a proxy for species
relationships,
and whether or not the pattern of amino acid replacements reveals
anything
about function or the process of molecular evolution.
19.
Doolittle, R. F., Feng, D-F., Tsang, S., Cho, G. and
Little, E. (1996) Determining divergence times of the major kingdoms of
living
organisms with a protein clock. Science
271, 470 - 477.
20. Glaser,
F., Pupko, T., Paz, I., Bell, R. E., Bechor-Shental,
D., Martz, E., and Ben-Tal. N. (2003)
Proteins
by Surface-Mapping of Phylogenetic Information.
Bioinformatics
19(1), 163–164
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Using Hemoglobin to Track Blood Lines