7 minutes
Published September 2015

How Does New Genetic Information Evolve? Part 1: Point Mutations

Description

Point Mutations

This film is the first of a two part series on the evolution of new genetic information. Here we focus on Point Mutations - the simplest natural mechanisms known to increase the genetic information of a population.

Our second film of the series will focus on duplication events - natural mutations that increase the total amount of genetic information of an individual.

Point mutations are small, natural edits in the DNA code of an individual. These edits can be passed from parent to child. Because they are mere edits, point mutations usually do not increase the total amount of information in an individual. As new information is gained, old information is lost. Point mutations do, however, increase the total amount of information within a population.

In this film you will see several examples of beneficial point mutations which have enhanced a creatures abilities or even given rise to entirely new abilities. The first two examples were directly observed in bacteria by scientists in the lab. The third is a case found in domestic dogs, the last example was discovered in several species of wild animal.

Details about mutation examples in this film:

Example 1: an observed point mutation is shown to increase the reproduction speed of E. coli in lab conditions 

Papers:

Dr Richard Lenski has been studying the evolution of bacteria in an experiment which has now been running for over 25 years! It's called the E. coli Long-term Experimental Evolution Project. Our first mutation example in the film outlines one of the many discoveries made by Lenski’s lab. A mutation known as allele pbpA-5 increased the reproduction rate of E. coli within the lab environment, allowing it to eventually out-compete all non-mutant individuals. This mutation is detailed in the second paper referenced above. 

Results strongly suggest that the pbpA-5 mutation occurred sometime after generation 500, and achieved total takeover (also known as fixation) by generation 2,000. In a previous paper (the first one cited above) they report the estimated generation rate for their non-mutant bacteria as being ~6.6 generations per day. Assuming the mutation may have occurred as early as generation 501, and takeover occurred as late as generation 2,000, the takeover would have occurred in less than one year - 228 days at most.

This mutation made the bacteria extremely efficient at reproduction in the lab where the mutation evolved. It's important to note, however, that this mutation seems to have weakened the bacteria's ability to survive in several wild environments. Tradeoffs like this are typical of point mutations - that which is beneficial in one environment might be a disadvantage in another.

Example 2: Gain-of-Function Mutation Observed In Salmonella Bacteria

Papers:

In 1976, David C. Old and Robert P. Mortlock reported a mutant version of Salmonella which evolved in one of their labs. The specific mutation was never isolated in the DNA due to sequencing limitations of that era, but the ease at which it evolved (they were able to coax it's evolution several times when starting with non-mutant Salmonella) suggests that it was a simple point mutation. The mutated strain of Salmonella typhimurium had gained the ability to detect and digest its normal food source (fucose) and a new foreign food source (d-arabinose) which wild-type Salmonella can not recognize as food. 

According to Michael Behe who revisited the discovery in 2010, this mutation is a rare example of a what he calls a “gain-of-functional-coded-element” mutation. This means that not only is it a gain of information for the population, like many point mutations are, it’s also a gain of information for the individual. It qualifies as such because the organism’s regulatory protein that initiates digestion appears to have gained an additional binding site for the new food source. 

Michael Behe’s classification of this mutation is significant because he, being both a solid biochemist and an Intelligent Design advocate, has created the strictest possible classification system for mutations.

Of this mutation Behe says: 

“An interesting variation on this pattern is reported in Chapter 5 by Lin and Wu (1984) [the book then refers to the 1976 study]. Mutants of E. coli and S. typhimurium (S. enterica var Typhimurium) gain the ability to metabolize the unusual substrate d-arabinose by altering the specificity of a regulatory protein. Normally, the enzyme fucose isomerase is induced in these bacteria when some fucose enters the cell and binds to a positive regulatory protein, which then turns on the gene for the isomerase. The regulatory protein of some mutants, however, responds to both fucose and d-arabinose. It turns out that the unusual substrate d-arabinose can be metabolized by enzymes of the fucose pathway, and, because the protein has apparently gained an additional binding site for the novel substrate, the mutation is classed as gain-of-FCT.”

See Michael Behe's paper for more information. In the paper he points out that most point mutations either modify existing information (meaning no net gain of info for the individual, only for the population) or they result in a loss of function by break a binding site which is not needed in a particular environment. 

Example 3: Evolution of new information for long hair in domestic dogs

Papers:

This study aimed to discover the mutations which code for three unique fur traits in domestic dogs: 

  • Furnishings (abnormally long facial hair) like that found in the Schnauzer
  • Long fur like that found in the Rough Collie
  • Curly fur like that found in the Poodle

Various combinations of these three traits are responsible for almost all variation of fur type found in dogs. 

In our film we focus on the second mutation - long fur - which appears to have been caused by a single point mutation in the FGF5 gene. This mutation turned a single G to a T in the genetic code. Evidence suggests that this mutation is the most common mutation for increasing fur length, though others do appear to exist. 

The long fur mutation is absent from all studied wolf populations and therefore appears to have evolved after the domestication of dogs.

Example 4: Resistance to toad toxins in wild lizard, snake and mammal populations

Several species of Toad produce a chemical in their skin called bufotoxin which kills most animals who try to eat them. It works by attaching to and clogging the Sodium-Potassium Pumps found in the membranes of animal cells. 

The Sodium-Potassium Pump is a protein machine which evolved early in animal history. Its exact amino acid sequence, shape, and function has been highly conserved by natural selection. The protein is nearly identical in almost all animals. That said, several different types of point mutations which change the amino acid sequence of the protein can occur without causing major damage to the pump. 

Dr Nicholas Casewell and colleagues have recently discovered that amino acid substitutions in two spots of the pump, make it so that bufotoxins cannot attach to and clog it. These mutations have have become fixed in several populations of predator animals that live along side toads, allowing them to eat the toads without consequence. 

Hedgehogs, after killing a toad for a meal, have even been observed rubbing the toxins on their own skin and fur, making them toxic to predators as well! 

Other Notes: 

What is the Human Mutation Rate?

Here you will find a series of review articles by Laurence A. Moran. In the series he summarizes several recent studies on Human Mutation Rates: Estimating the Human Mutation Rate

These studies give us a variety of mutation rate estimations which range from 56 to 160 point mutations per generation. In our film, we chose to say "roughly 70 point mutations" per generation as this is a conservative estimate close to the mid range of most studies.

Are Mutations Truly Random?

Point mutations are largely random in that they can occur anywhere within the genome and are not reasonably predictable. Certain parts of the genetic code, however, are naturally more vulnerable to mutation than others. Furthermore, the cells of some organisms, including certain human cells, have the ability to increase the relative mutation rates of specific genes when needed. This appears to be done by simply neglecting to repair natural damage to those stretches of DNA though other mechanisms may also be involved. 

Research into the human immune system has found that B cells (those which produce antibodies for the immune system) can purposely increase the mutation rate of their antibody genes by up to 1 million fold. They do this without increasing the mutation rates of their normal housekeeping genes. This high mutation rate allows them to quickly evolve an antibody that will effectively detect a specific invader.

Bacteria appear to have a similar mechanism allowing them to increase or decrease the mutation rates of specific stretches of DNA. The mechanisms involved are only just beginning to be understood.