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The Genetics of Evolution

We are the Results of Ancient Selection

The discovery of neutral evolution has actually provided a powerful tool for determining whether a particular gene has been under natural selection pressure or not. By comparing the ratio of non-silent to silent mutations in a particular gene, scientists can determine whether that gene has been under selective pressure.

Purifying Selection
If a gene codes for a protein so vital that even small changes to its function are lethal, then only non-lethal mutations will accumulate.
One might reasonably expect a such a critical protein to have NO non-silent mutations, though it may have some silent ones.
This gene has undergone purifying selection, which has, figuratively "purified" the gene by removing any deleterious variations.

In a gene that has undergone purifying selection, the ratio of nonsilent to silent mutations (NS/S) should be ZERO. (NS, the numerator, is zero)


Neutral Genetic Drift
If a gene is not influenced at all by natural selection, one would expect silent and non-silent mutations to accumulate at an equal rate, since neither kind of mutation matters to the gene's function (or lack thereof).

In a gene changing only due to random chance (genetic drift), the ratio of nonsilent to silent mutations (NS/S) should be ONE (NS = S).


Positive Selection
If a gene product's function is a little less rigid, then mutations may be tolerated, resulting in new alleles of that product/protein. Some of the non-silent mutations may result in alleles that function better under certain conditions than other alleles, and these will be naturally selected.

In a gene changing due to natural selection, the ratio of nonsilent to silent mutations (NS/S) should be GREATER THAN ONE (NS > S).


Positive Selection in the Primate Genome: Making us Human?
A study examining entire genomes of monkeys and apes found that of more than 10,000 genes examined, 9.8% of the proteins were conserved, with NO non-silent mutations, and 2.2% of the proteins showed evidence of positive selection.

A protein known as Forkhead box protein P2, or FOXP2 is widely distributed among vertebrates, and existing in various forms in mammals.

In the central nervous system (brain and spinal cord), the FOXP2 protein

  • Baby mice with normal FOXP2 genes squeak to get their mother's attention and care. Scientists have artificially "knocked out" the FOXP2 gene in mice and produced baby mice unable to squeak normally. (How might this be a selective disadvantage?)

  • Humans with mutant versions of FOXP2 have severe language and speech disabilities, and are unable to understand grammar or language construction.

  • FOXP2 in mice and great apes is nearly identical in both gene sequence and function.

  • In humans, however, two non-silent mutations that have occurred somewhere in the past 6 million years have modified the proteins function in a major way that is not fully understood.

    Could our species' capacity for language--one of the things that makes it so unique--be due to just two small mutations?

    By performing studies like this, and finding genes that show strong evidence of natural selection, we may be able to home in and discover their functions.

    But even more interesting to the evolutionary biologist, studying changes in genes can allow us to monitor how they have evolved from ancestral genes through a process of accidental duplication followed by recruitment for a new function

    Gene Duplication and Gene Recruitment: Step One

    One often hears the anti-evolution claim that "you can't add genetic information" to the genome.

    This is entirely wrong.

    Just as morphological innovations come from pre-existing structures, new genes also come from pre-existing genes.

    Recall that before any cell divides, it must duplicate all its structures to make two new, identical copies of itself during mitosis. This includes the important process of DNA replication.

    And as we already know, mistakes can be made during (1) DNA replication or during (2) crossing over at meiosis (unequal crossing over). Possible results:

    And any of these mutations can be

    Genomes of living species bear copious evidence of permanent inactivation of once-functional genes. These are called pseudogenes. They can be recognized by the presence of the usual "start" and "stop" codons at either end. They are no longer transcribed or translated. Let's focus for a moment on a relatively common phenomenon for which we see evidence in many species' genomes, duplication

    This could result in the overproduction of the gene products of the duplicated genes.
    But each of these duplicated genes is now subject to mutations that could well leave the original gene intact.
    In effect, these "extra" genes become the raw material for new functions that arise via mutation.

    Is gene duplication beneficial? Deleterious? Neutral?
    The actual identity of the gene products and their functions will determine this.
    If the duplication is lethal, then the organism will not pass it on. End of story. But what if the duplication is NOT lethal?

    Here are three possible scenarios, post-gene duplication...


    The enlistment of a changed/mutated version of a gene for a function that's different or somewhat different from the original function is known as gene recruitment.

    Gene Duplication --> Gene Recruitment --> Evolutionary Innovation

    In our own lifetime, we have seen both wild and laboratory incidences of mutations leading to evolutionary innovation and natural selection.
    We also can see evidence that similar sequences of gene duplication followed by gene recruitment (i.e., using the duplicate gene for a somewhat changed or entirely new function) has been instrumental in the evolution of such diverse, complex structures as snake venom delivery apparatus and vertebrate eyes.

    6. PCP-feeding Sphingobium

    Pentachlorophenol (PCP) is a toxic, carcinogenic compound first developed as a fungicide in the 1930s.
    It has since contaminated soils and entered water tables, where it can be ingested by living organisms, including humans.

  • Sphingobium species are ubiquitous soil bacteria.
  • A strain was discovered that could break down PCP into harmless components, and harvest the energy of the covalent bonds. The bacteria were using the PCP as food.
  • They were able to do this with special enzymes that
  • The new enzymes are chemically very similar to enzymes that break down amino acids in the original (wild type) Sphingobium.
  • The metabolic enzyme pathway required to break down PCP probably occured in several steps, but it is fully functional now
  • This happened since the 1930s, when PCP first entered the environment.
  • The bacteria are now using new genes--derived from pre-existing enzyme-coding genes--to make PCP-cutting enzymes.

    Evolution of Genes from Pre-existing Genes

    Gene duplication is not the only mechanism by which genomes can increase in size and change in function.
    In some cases, gene rearrangement can instigate the evolution of a gene with an entirely new function. Definition:

    Modification of Gene Expression Can Change Phenotype

    Mutations that change the identity of a protein are not the only way to change phenotype. Sometimes, a mutation can change the timing of gene expression, and/or the degree to which a gene is expressed. This can sometimes have dramatic results.

    Recall the Central Dogma of gene expression:

    DNA is transcribed into RNA, and RNA is translated into protein

    Transcription Factors

    Recall that a transcription factor is a protein that binds to a specific DNA sequence and controls how that segment of DNA is read.

    Our Friend the Gene.

    Remember that all these stretches are nucleotide sequences, and they can mutate.

    Watch a short, clear video of transcription to get an idea of how this works.

    Mutations in any of these regions can increase the production of a gene product, decrease it, or shut it off.

    Early Development

    As a zygote develops and undergoes its orderly cleavages, the DNA in each new cell is repackaged and modified:

    As the genetic instructions guiding a vertebrate embryo's development change in each new cell, the cells themselves follow those instructions, and are modified...

    All of this is governed by instructions on the DNA. Each cell has the same genome, but different genes are active and inactive in each type of cell.

    Hox Genes and Genetic Toolkits

    Every animal embryo has a set of genes that determines its body axes, morphology, segmentation, limbs, and other features. This has been called the Genetic Toolkit.

    Among these are the Hox Genes that determine the identity of the body segments in animals as diverse as fruit flies and mammals. How did these toolkits expand to make such different organisms? Duplication and Recruitment, as we have seen before. The Hox genes in fruit flies and mammals are homologous: inherited from a common ancestor.

    In the two major lineages of animals, protostomes and deuterostomes, whom we have met before, major organ systems (circulatory, digestive, and nervous) are reversed in body position:

    Yet the genes that determine where these systems will develop are HOMOLOGOUS.

    Changing Gene Activity Can Change Phenotype

    We've already seen the variety of beak shapes and sizes in Darwin's finches. How can such major differences happen?

    The second column shows developing beaks of bird embryos. Dark areas indicate cells expressing a gene product known as BMP4 ("Bone Morphological Protein 4").

    The third column shows developing beaks of bird embryos. This time they are stained to show expression of a gene product known as calmodulin.

    Red areas show regions of very high levels of expression.

  • Low level of BMP4 promotes a long, narrow beaks.
  • High level of BMP4 promotes a wide, deep beak.
  • Calmodulin controls the length of the beak. (low levels = short; high levels = long)

    Both bmp4 and calmodulin genes control other embryo development functions.
    In some cases, a simple change that changes the activity of a promoter, enhancer or repressor can make a huge difference in a system like this one.

    Another example can be seen in the different expression of two proteins--BMP2 and Shh--in disks of skin cells called placodes in embryonic reptiles (including birds).

    Different levels of expression of the two proteins in placodes can cause development of scales, tubular feathers, branched feathers, or a feather with a central rachis.

    Modern kiwis have simple tubular feathers, and are flightless.
    It's possible that the first feathers were tubular structures that aided in insulation, and that small mutations caused them to "feather".

    Convergent Evolution

    The evolution of two unrelated lineages towards a similar or parallel form is known as convergent evolution. A few examples...

    The developmental genetic programming for these convergences must often start with different "raw materials."

    New structures and genes must arise from ones that already exist.
    There is no end to the grandeur of evolution.