We can learn about how they evolve from studies of sequence divergence between proteins from homologous organisms.

Refers to any similarity between characteristics that is due to their shared ancestry.

Homologs produced by speciation. They tend to have similar function.

Homologs produced by gene duplication. They tend to have differing functions.

Homologs resulting from horizontal gene transfer between two organisms.

Orthologs

Paralogs

Xenologs

Early globin gene

mouse

ß-chain gene -chain gene

cattle ß human ß mouse ß human cattle

Orthologs () Orthologs (ß) Paralogs (cattle)

Homologs

Orthologous or Paralogous Homologs

The process of change in all forms of life over generations.

Adaptation.

Mutation (very slow).

Natural selection (causes adaptive evolution).

Nuetral drift (chance; causes nonadaptive evolution).

Four Force of Evolution

Is the change in living organisms that allow them to

live successfully in an environment.

The Oxford Dictionary of Science defines adaptation as

"Any change in the structure or functioning of an

organism that makes it better suited to its environment ."

Adaptation

Type of Mutation

Change in primary amino acid sequence

Mutation

A. Silent mutations

B. Point mutations

Type of Mutation

A. Silent mutations Code for the same amino acid.

B. Point mutations

Change in only one pair of nucleotid as follows:

Nonsense mutations: Code for a stop, which stop protein formation(UAA, UGA, UAG).

Frameshift mutation: Addition or deletion of bases leading to altered sequence beyond the sequence

change.

Missense mutations: Code for a different amino acid.

a process causing heritable traits that are helpful for survival and reproduction to become more common in a population, and harmful traits to become more rare.

Natural Selection

This occurs because individuals with advantageous traits are more likely to reproduce,

so that more individuals in the next generation inherit these traits.

Genetic drift results from the role probability plays in whether a given trait will be passed on individuals survive and reproduce.

Neutral Drift

Is an dependent process that produce random changes in the frequency of traits in a population.

In a large population this will not have much effect in each generation because the random nature of the process will tend to average out.

But in a small population the effect could be rapid and significant.

Evolution

Chemical Evolution

Structural Evolution

The evolutionary aspects of amino acid sequences. Evolutionary changes, which stem from random muational events, often alter a protein’s primary structure.

Chemical Evolution

Transport oxygen through body . Has 4 subunits: α2β2. Contained in red blood cells at high concentration. RBC is flexible biconcave disks and has to contort to fit through small sized capillary sections.

Sickle Cell Anemia :The Influence of Natural Selection

Hemoglobin

Sickle Cell Anemia :The Influence of Natural Selection

RBC assume crescent-like shape under low oxygen concentration. More rigid and hinders free passage. Molecular disease :Term coin by Linus Pauling. Caused by mutant hemoglobin.

Sickle cell anemia

Replacement of a negatively-charged glu in the standard HbA by a neutral val in HbS results in a protein with a slightly reduced negative charge.

Electrophoretic studies show that sickle cell hemoglobin HbS is two units more positive than HbA (normal).

Sickle cell trait follow Mendelian genetics. Homozygotes have hemoglobin with all HbS Heterozygotes have approx. 40% HbS. Such people have sickle cell trait and can lead normal life. Anthony Allison Led to discovery that individuals heterozygote are resistant to malaria.

Sickle cell confers resistance to malaria

Malaria caused by protozoan Plasmodium Falciparum.

Plasmodia increase acidity of erythrocytes they infect by ~0.4 PH units. This causes erythrocytes to adhere to proteins lining capillary walls and thus avoid removal from spleen.

Normally, ~2% of erythrocytes of those with sickle cell trait are sickle under low oxygen tension.

How does Sickle Cell Confer resistance to Malaria?

With sickle cell trait, the decrease in pH causes increase in sickled cell shape of up to ~40%. This causes preferential removal of infected cells. The sickling induced by this low oxygen environment cells may mechanically and/or metabolically disrupt the parasite. Heterozygotes have advantage in surviving malaria.

How does Sickle Cell Confer resistance to Malaria?

Environment With Malaria Parasite HbA HbA are normal but die of malaria HbS HbS die HbA HbS display symptoms of sickle cell anemia but are resistant to malaria

Sickle Cell Anemia and Malaria

Environment Without Malaria HbA HbA are normal HbS HbS die HbA HbS display symptoms of sickle cell anemia

Species Variations in Homologous Protein :The Effects of Neutral Drift

To examine homologous proteins and study an example of an orthologue.

To use the Biology Work Bench to comparin Cytochrome C from a variety of different species.

To apply genetic understanding to explain how different orthologues proteins can arise.

Cytochrome c: an Orthologue

Cytochrome c has a single polypeptide chain an ancient protein, developed early in the evolution of life.

It occurs in mitochondria as part of the electron transport chain.

Consist of 103 or 104 residues, but in other phyla has up to 8 additional residues at its N-terminus.

It has changed little in millions of years of evolution.

Elucidated the amino acid sequences of cytochromes c from over 100 widely diverse eukaryotic species ranging in complexity from yeast to humans.

The sequences from 38 of these organisms are arranged in table so as to maximize the similarities between vertically aligned residues .

Man, chimpanzee DTLMEYLENPKKYIPGTKMIFVG

Rhesus monkey DTLMEYLENPKKYIPGTKMIFVG

Horse ETLMEYLENPKKYIPGTKMIFAG

Donkey ETLMEYLENPKKYIPGTKMIFAG

Cow, pig, sheep ETLMEYLENPKKYIPGTKMIFAG

Dog ETLMEYLENPKKYIPGTKMIFAG

Rabbit DTLMEYLENPKKYIPGTKMIFAG

Calif. gray whale ETLMEYLENPKKYIPGTKMIFAG

Great gray kangaroo DTLMEYLENPKKYIPGTKMIFAG

Chicken, turkey DTLMEYLENPKKYIPGTKMIFAG

Pigeon DTLMEYLENPKKYIPGTKMIFAG

Pekin duck DTLMEYLENPKKYIPGTKMIFAG

Snapping turtle ETLMEYLENPKKYIPGTKMIFTG

Rattlesnake DTLMEYLENPKKYIPGTKMVFTG

Bullfrog DTLMEYLENPKKYIPGTKMIFAG

Tuna DTLMEYLENPKKYIPGTKMIFAG

Dogfish ETLRIYLENPKKYIPGTKMIFAG

Samia cynthia (moth) DTLFEYLENPKKYIPGTKMVFAG

Tobacco hornworm moth DTLFEYLENPKKYIPGTKMVFAG

Screwworm fly DTLNPKLENPKKYIPGTKMIFAG

Drosophila (fruit fly) DTLFEYLENPKKYIPGTKMIFAG

Baker’s yeast NNMSEYLTNPKKYIPGTKMAFGG

Candida krusei (yeast) PTMSDYLENPKKYIPGTKMAFGG

Neurospora crassa (mold) NTLFEYLENPKKYIPGTKMAFGG

Wheat germ NTLYDYLLNPKKYIPGTKMVFPG

Buckwheat seed DTLYEYLLNPKKYIPGTKMVFPG

Sunflower seed NTLYDYLENPKKYIPGTKMVFPG

Mung bean KTLYDYLENPKKYIPGTKMVFPG

Cauliflower KTLYDYLENPKKYIPGTKMVFPG

Pumpkin KTLYDYLENPKKYIPGTKMVFPG

Sesame seed NTLYDYLENPKKYIPGTKMVFPG

Castor bean NTLYAYLENPKKYIPGTKMVFPG

Cottonseed NTLYDYLENPKKYIPGTKMVFPG

Abutilon seed NTLYDYLENPKKYIPGTKMVFPG

1 6 10 14 17 18 20

Human Gly Asp Val Glu Lys Gly Lys Lys Ile Phe Ile Met Lys Cys Ser Gln Cys His Thr Val Glu Lys

Pig - - - - - - - - - - Val Gln - - Ala - - - - - - -

Chicken - - Ile - - - - - - - Val Gln - - - - - - - - - -

Dogfish - - - - - - - - Val - Val Gln - - Ala - - - - - - Asn

Drosophila

<<

< - - - - - - - - Leu Val Gln Arg Ala - - - - - - Ala

Wheat <<

< - Asn Pro Asp Ala - Ala - - - Lys Thr - - Ala - - - - - Asp Ala

Yeast <<

< - Ser Ala Lys - - Ala Thr Leu - Lys Thr Arg - Glu Leu - - - - - -

In table indicates that cytochromes c is an evolutionarily conservative protein. a total of 38 of its 105 residues (23 in all that have ben sequenced)are invariant and most of the the remaining residues are conservative substituted.

In contrast, there are 8 position that each accommodate six or more different residue and, accordingly, are described as being hypervariable.

However, the biochemical significance of most of the

invariant or conservatively substituted residues of cytochrom c can only be profitable assessed in term of the protein s three dimensional structure .

The easiest way to comare the evolutionary differnces between two homologous protein is simply to count the amino acid differences between them .

we can tabulation of amino acid sequances differences among 22 of the cytochromes c listed in table.

Thus primate cytochromes c more nearly resemble those of other mammale than they dof,or example, those of insect(8-12 differences for mammals vs 26-31 for insect).similarly, the cytochromes c of fungi differ as much from those of mammals (41-47) or higher plants (47-54).

We can analysis of data such as those in table aphylogenetic tree can be constructed that indicates the ancestral relationships among the organisms which produced the protein .

Displays a phylogenetic tree (a diagram illustrating the evolutionary relationships among a group of organisms) constructed from the sequences of cytochrome c.

The tree has been deduced by computer analysis of these sequences to find the minimum number of mutational changes connecting the branches.

Similar tree have been derived for other protein. Each branch point of a tree indicates the probable existence of common ancestor for all the organisms above it.

The relative evolutionary distances between neighboring branch point are expressed as the number of amino acid differences per 100resides of the protein .

This furnishes a quantitative measure of the degree of relatedness of the various species that macroscopic toxonomy cannot provide .

Evolutionary trees constructed in this manner, that is, solely on the basis of amino acid differences occurring in the primary sequence of one selected protein, show remarkable agreement with phylogenetic relationships derived from more classic approaches and have given rise to the field of molecular evolution.

Evolution of

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References

1.X. Gu, "Statistical methods for testing functional divergence after gene 2.duplication" Mol. Biol. Evol. 16:1664-1674 (1999). 3.www_bio_mtu_edu-campbell-401l10f4_gif. 4.http--www_asa3_org-aSA-PSCF-1992-PSCF12-92MillsFig3_jpg.mht 5.http--anthro_palomar_edu-synthetic-images-map_of_sickle_cell_frequencies_gif.mht 6.http--fig_cox_miami_edu-~cmallery-150-gene-sf12x16_jpg.mht 7. http--mvl_chem_tu-berlin_de-ak_hildebrandt-hildebrandt-images-Cyt_1_jpg.mht . 8. http--www_detectingdesign_com-images-Methinks cytochrome%20c_jpg.mht 9. http--dbs_umt_edu-courses-fall2006-bioc380-lectures-009-images-cyt-c-seq_jpg.mht 10.http--www_muhlenberg_edu-depts-biology-courses-bio152 BioinformaticsLab-symptoms_gif.mht 11.http--academic_brooklyn_cuny_edu-biology-bio4fv-pag molecular%20biology-mutation-neutral_jpeg.mht 12.http://philosophy.wisc.edu/forster/220/notes_4.html

13.lhttp://philosophy.wisc.edu/forster/220/notes_4.html

Thank you