1. Molecular and Genomic Evolution

2. Molecular and Genomic Evolution
Genomes and Their Evolution
The Evolution of Macromolecules
Determining and Comparing the Structure of Macromolecules
Proteins Acquire New Functions
The Evolution of Genome Size
The Uses of Molecular Genomic Information

3. Genomes and Their Evolution
An organism’s genome is the full set of genes it contains.
In eukaryotes, most of the genes are found in the nucleus, but genes are also present in plastids and chloroplasts.
Genes are shuffled in every generation of sexually reproducing organisms via meiosis and fertilization.

4. Genomes and Their Evolution
For a gene to be passed on to successive generations, the individual with that gene must survive and reproduce.
A gene’s capacity to cooperate with different combinations of other genes will likely increase its probability of transmission.
The genes of an individual can be viewed as interacting members of a group in which there are divisions of labor and strong interdependencies.

5. Genomes and Their Evolution
Studies of genomic evolution look at the genome of an organism as an integrated whole and attempt to answer questions such as:
How do proteins acquire new functions?
Why are the genomes of different organisms so variable in size?
How has the enlargement of genomes been accomplished?

6. The Evolution of Macromolecules
The molecules of interest to molecular evolutionists are nucleotides, nucleic acids, amino acids, and proteins.
Molecular evolutionists investigate the evolution of these macromolecules to determine how rapidly they change and why they have changed.
Knowledge of the rate of change of a given macromolecule is crucial to attempts to reconstruct the evolutionary history of groups of organisms.

7. The Evolution of Macromolecules
Nucleic acids evolve when nucleotide base substitutions occur.
Substitutions can change the amino acid sequence, and thus the structure and function, of the polypeptides.
By characterizing nucleic acid sequences and the primary structures of proteins, molecular evolutionists can determine how rapidly these macromolecules have changed and why they changed.

8. The Evolution of Macromolecules
Molecular evolution differs from phenotypic evolution in one important way: In addition to natural selection, random genetic drift and mutation exert important influences on the rates and directions of molecular evolution.
A mutation is any change in the genetic material.

9. The Evolution of Macromolecules
Many mutations, called silent or synonymous mutations, do not alter the proteins they encode.
This is because most amino acids are specified by more than one codon in the universal genetic code.
For example, leucine is specified by six different codons: UUA, UUG, CUU, CUC, CUA, and CUG.
Since silent mutations are unlikely to be influenced by natural selection, they are free to accumulate in a population over time at rates determined by rates of mutation and genetic drift.

10. The Evolution of Macromolecules
A nonsynonymous mutation does change the amino acid sequence.
For example, UUA to UUC would result in a phenylalanine rather than a leucine in the protein.
Nonsynonymous mutations are usually deleterious, but those that don’t alter the protein’s shape may be selectively neutral.
Most natural populations of organisms harbor much more genetic variation than would be expected if genetic variation were influenced primarily by natural selection.

11. Figure 26.1 When One Base Does or Doesn’t Make a Difference

12. The Evolution of Macromolecules
In 1968, Motoo Kimura proposed the neutral theory of molecular evolution.
The neutral theory postulates that, at the molecular level, the majority of mutations are selectively neutral.
If so, the majority of evolutionary changes in macromolecules, and much of the genetic variation within species, result from neither positive selection of advantageous alleles nor stabilizing selection, but from random genetic drift.

13. The Evolution of Macromolecules
Using the rationale that the rate of fixation of mutation is theoretically constant and equal to the neutral mutation rate, the concept of the molecular clock was developed.
The concept of the molecular clock states that macromolecules should diverge from one another at a constant rate.

14. Determining and Comparing the Structure of Macromolecules
Biologists must determine the precise structure of macromolecules to investigate patterns of molecular evolution.
PCR allows biologists to amplify ancient DNA to concentrations that can be used in experiments to determine its sequence.
When the amino acid sequences of proteins from different organisms have been determined, they can be compared by sequence alignment.

15. Figure 26.2 Amino Acid Sequence Alignment (Part 1)

16. Figure 26.2 Amino Acid Sequence Alignment (Part 2)

17. Determining and Comparing the Structure of Macromolecules
Once the amino acid sequences have been aligned, they can be compared.
A similarity matrix can be constructed by adding up the number of similar and different amino acids in the sequences.
The longer the molecules have been evolving separately, the more differences they will have.
Substitution rates are highest at codon sites that do not change the amino acid being expressed, and in pseudogenes.

18. Figure 26.3 Rates of Base Substitution Differ

19. Determining and Comparing the Structure of Macromolecules
The much slower rate of mutation at sites that do affect molecular function is consistent with the view that most nonsynonymous mutations are disadvantageous and are eliminated from the population by natural selection.
In general, the more essential a molecule is for cell function, the slower the rates of its evolution.
A molecule that illustrates this principle is the enzyme cytochrome c, a component of the respiratory chain in mitochondria.

20. Figure 26.4 Amino Acid Sequence of Cytochrome c (Part 1)

21. Figure 26.4 Amino Acid Sequence of Cytochrome c (Part 2)

22. Determining and Comparing the Structure of Macromolecules
To function as a molecular clock, a macromolecule would need to evolve at an approximately constant rate in all evolutionary lineages.
Cytochrome c sequences have evolved at a relatively constant rate.
Many other proteins show similar consistency in the rate at which they have changed over time, but not all molecules change at the same rate.

23. Figure 26.5 Cytochrome c Has Evolved at a Constant Rate

24. Determining and Comparing the Structure of Macromolecules
Organisms with short generation times generally have faster rates of molecular evolution than organisms with longer generation times.
Shorter generations result in more rounds of DNA replication and thus more opportunity for errors in replication.
The rate of substitution per base per year in introns is 2 to 4 times greater in rodents than in primates.

25. Proteins Acquire New Functions
Evolution would not have been possible if proteins were unable to change their functional roles.
Evidence indicates that all living organisms arose from a single ancestral lineage.
Thus the many thousands of different functional genes that exist today must have arisen from a small number of ancestral genes.

26. Proteins Acquire New Functions
The most important process enabling proteins to acquire new functions appears to be gene duplication.
Gene duplication may involve part of a gene, a single gene, parts of a chromosome, or whole chromosomes.
Polyploidy, the duplication of an entire genome, has been important in speciation.
Autopolyploid individuals avoid imbalances in gene expression because all of their chromosomes are duplicated.

27. Proteins Acquire New Functions
Evolution of a new function for a protein:
Lysozyme is an enzyme found in almost all animals; it digests bacterial cell walls and is the first line of defense against invading bacteria.
In mammals, a mode of digestion known as foregut fermentation has evolved twice. Bacteria in the foregut break down ingested plant matter by fermentation.
In foregut fermenting animals, lysozyme has been modified to play a nondefensive role.
The enzyme ruptures some of the bacteria that live in the foregut, releasing nutrients that the animal absorbs.

28. Table 26.1 Similarity Matrix for Lysozyme in Mammals

29. Proteins Acquire New Functions
Five amino acid substitutions are shared by foregut fermenters (cow and langur).
The substitutions make it more resistant to the pancreatic enzyme trypsin and the acidic conditions of the stomach.
Similar substitutions of hoatzin lysozyme have occurred to provide a similar function as cow and langur lysozyme.
These three groups of animals independently evolved a similar molecule that enables them to recover nutrients from their fermenting bacteria.

30. The Evolution of Genome Size
The size and composition of the genomes of many species show much variation.
Multicellular organisms have more DNA than single-celled organisms.
Generally, more complex organisms have more DNA than less complex organisms.

31. Figure 26.7 Complex Organisms Have More Genes than Simpler Organisms

32. The Evolution of Genome Size
Some of the apparent differences in genome size disappear when the portion of DNA that actually codes for RNA or protein is compared.
The size of the coding genome varies in a way that makes sense:
Eukaryotes have more coding DNA than prokaryotes.
Plants have more than single-celled organisms.
Vertebrates have more than nonvertebrates.

33. The Evolution of Genome Size
Most of the variation in genome size is due to the amount of noncoding DNA an organism has.
Much of the noncoding DNA may consist of pseudogenes that are carried with the genome because the cost of doing so is small.
Some of the DNA consists of transposable elements that spread through populations because they reproduce faster than the host genome.

34. Figure 26.8 A Large Proportion of DNA Is Noncoding

35. The Evolution of Genome Size
Retrotransposons are being used by scientists to determine the rates at which species lose DNA.
The most common type carries long terminal repeats (LTRs) at each end.
Occasionally, LTRs join together in the host genome, causing the DNA between them to be excised and leaving one of the LTRs behind.
The number of these “orphaned” LTRs in a genome is a measure of how many retrotransposons have been lost.
Scientists can use the number of LTRs present in the genomes of different organisms to compare their rates of DNA loss.

36. The Evolution of Genome Size
Two identical copies of a gene can have one of three different fates:
Both copies may retain their original function.
One copy may become incapacitated by the accumulation of deleterious mutations and become a pseudogene.
One copy may retain its original function while the other accumulates enough mutations that it can perform a different function.
The third is the most significant for evolution.

37. The Evolution of Genome Size
The frequency of gene duplications and their outcome can be assessed by counting the number of synonymous nucleotide base changes in the genome and then comparing that with the number of base changes causing protein alterations.
The rates of gene duplication are fast enough for a yeast or Drosophila population to acquire several hundred duplicate genes over the course of a million years.
Although most duplicate genes disappear rapidly on an evolutionary time scale, some duplications lead to the evolution of genes with new functions.

38. The Evolution of Genome Size
Several rounds of duplication and mutation may lead to formation of a gene family, a group of homologous genes with related functions.
There is evidence that the globin gene family arose by gene duplication.
To estimate the time of the first globin gene duplication, a gene tree can be created.
Based on the gene tree, the two globin gene clusters are estimated to have split about 450 mya.

39. Figure 26.9 A Globin Family Gene Tree

40. The Uses of Molecular Genomic Information
Molecules that have evolved slowly can be used to estimate relationships among organisms that diverged long ago.
• Molecules that have evolved rapidly are useful for studying organisms that share recent common ancestors.
To determine the molecular evolutionary relationships of all existing animals, a molecule that all organisms possess must be used, such as rRNA.

41. The Uses of Molecular Genomic Information
rRNA has evolved very slowly because even minor changes in its base sequence result in inactive ribosomes.
Differences among the rRNAs of living organisms can be used to estimate the timing of lineage splits.
Molecular, morphological, and fossil data are regularly used in combination to create a phylogeny.
The more characters that are used to create a phylogeny, the more accurate it will be.

42. The Uses of Molecular Genomic Information
Genes found in different organisms that arose from a single gene in their common ancestor are called orthologs.
Genes that are related through gene duplication events in a single lineage are called paralogs.
All of the genes in the engrailed gene family are orthologs.
Paralogous engrailed genes have been generated in some lineages as a result of duplication events.

43. Figure 26.10 Phylogeny of the Engrailed Genes

44. The Uses of Molecular Genomic Information
Understanding the genomes of pathogens and the organisms that carry them has already had medical benefits.
The determination of the genomes of Anopheles and Plasmodium has allowed scientists do develop transgenic mosquitoes that express an anti-Plasmodium molecule that makes them inefficient vectors of malaria in the lab.
Information provided by the genomic sequence of Treponema pallidum, the bacterium that causes syphilis, is being used to develop a vaccine against this disease.

45. The Uses of Molecular Genomic Information
The AIDS epidemic reminds us that molecular data, while providing powerful tools in our struggle with diseases, cannot solve all medical problems.
A highly active antiretroviral therapy (HAART) is generally used to treat AIDS patients.
Unfortunately, strains of resistant HIV develop in the blood of most patients that receive HAART.
The combination of a high mutation rate and no repair mechanism means that a new mutant is generated every time HIV replicates its genome.

46. The Uses of Molecular Genomic Information
Scientific understanding of the evolutionary patterns of life on Earth and how the agents of evolution governed those patterns is advancing more rapidly than ever.
By combining molecular data with information from the fossil record, biologists are developing an increasingly comprehensive picture of the evolution of life on Earth.