What's New In Science - Understanding Evolution Through Genomes

Randal Voss - The human genome project pushed science to develop novel DNA sequencing approaches that rapidly and inexpensively allow decoding of whole genomes. This effort is finely resolving details of genome structure, variation, and function at a rapid pace, and this massive amount of information is beginning to reveal new insights about the way genomes evolve. An important early message deriving from this work is that we need to look beyond natural selection, the predominant evolutionary process that we teach our students, to understand how genomes evolve. We need to better emphasize in our curricula the role of non-adaptive processes – mutation, genetic drift, and recombination – and how they also shape evolution.

Q&A:

Are there conditions which are more favorable for mutations to occur?

Yes. It has long been known that short-wave length radiation (e.g. UV, x-rays) can damage DNA and cause mutations. Also, when cells are stressed, oxidizing molecules (i.e. Reactive Oxygen Species) are created that are damaging to DNA. In some organisms it has been shown that stress increases the activity of transposable elements in the genome - in other words, they are are more likely to jump from one place in the genome to another, potentially disrupting gene sequences where they land. Recent studies of mutation rates between human male and female germ lines show a higher mutation rate in males vs females. Also, the mutation rate in somatic human cells is considerably higher than in germinal cells. And it has long been known that some regions along chromosomes are more mutable than other regions. There are other examples.

How large of an effect do genomes truly have in understanding evolution?

During evolution, genetically-based characteristics of populations change over time. The genetically-based characteristics of populations are encoded in the genome. Thus it stands to reason that we need to understand how genome evolve to understand how the characteristics of species evolve.

Can we understand evolution without reference to genomes?

Of course. Charles Darwin originated the theory of evolution by natural selection without knowledge of DNA. We can infer (without knowledge of genomes) that evolution happened in the past by comparing skulls of modern humans to the skulls of our close extinct relatives, like Homo erectus. It doesn't require that we compare the genomes of H. sapiens and H. erectus to draw this conclusion, but differences in the skulls almost certainly required genome level changes. Much modern research is directed at this level of inquiry because we have the tools to associate evolution of characteristics to changes in the genome. Genomes provide millions and billions of characters (nucleotides) from which to examine the process of evolution. This is a much richer collection of information to investigate evolutionary processes, than say the relatively few fossils that reveal our own evolutionary history.

How are some species able to change gender with an environmental cue? What do the genomic studies tell us about gender determination?

In some groups of animals (reptiles, fish), we see both sex determination mechanisms - environmental and genetic. Genetic sex determination ranges from single locus determination (alternate alleles segregating at a single locus on an autosomal chromosome) versus segregation of loci on distinct sex chromosomes, versus polygenic. Some fish are capable of changing gender in response to cues they receive from the environment about the number of male and female individuals in the population. These cues are processed in the brain and then hormones are released to cause maturation of the appropriate sex organs.

Are rates of cancer higher in animals that have the ability to regenerate limbs?

Amphibians, like the salamanders I study, rarely show cancer. It is not clear how salamanders are able to activate arrested cells after limb amputation and direct them to follow a controlled cell proliferation phase followed by a differentiation stage that restores lost tissues. Seems like they would often develop cancer, but they don't.

How might schools begin to integrate non-adaptive process of evolution into their program without running the risk of giving students false or incomplete information? (Aka misconceptions) What are the expected benefits of studying non-adaptive evolution?

There is nothing false or misleading about the affects of mutation and genetic drift on evolution. These theories are well established and accepted by the biology community. Misconceptions arise from ignorance, lack of information, and close-mindedness.....a common misconception, for example, is that evolution happens for a purpose. Misconceptions arise when you pick and choose what material is delivered to students. To answer the second part of your question, the benefit is that you study all concepts of evolutionary biology, not just some of the concepts. Turns out, when we examine DNA and ask if there is evidence of adaptation, we evaluate what we observe against a model that assumes non-adaptive evolution. In other words, non-adaptive evolution provides the null model for identifying evidence of adaptive evolution at the DNA level. You can't study one without the other.

What theories are there concerning the reason as to why organism store genetic information as DNA?

It is thought that the very first "living" organisms had an RNA-based genome. RNA performs the function of encoding information and RNA molecules can perform enzymatic reactions like proteins. So RNA provides the best of both worlds. However, in comparison to DNA, RNA is less stable....perhaps this explains the evolution of DNA based life. Also, transitioning to DNA based life and protein synthesis allowed a more diverse set of enzymatic reactions.

Has the process of evolution itself evolved?

Our theories of evolution have evolved for sure. Darwin's theory of natural selection was given a genetic basis in the 1930s, for example. If your question concerns rates of evolution, then yes, the rate of evolution can vary within lineages and across time.

Which of the non-adaptive roles has the most prevalence in genomic evolution?

Mutation alters the structure of genomes and genetic drift affects the probability that mutations will be lost or fixed within and among populations, as a result of chance. Both processes are important in evolution. Most types of mutation occur at very low rates, so it takes a long time for mutation to alter the structure of genomes. For those mutations that are neutral in their effect on fitness (survival, reproductive success), genetic drift largely determines their dynamics - the probability of their fixation/retention in the genome and the amount of time it takes for this process to take.

Some about salamander research:

Is the regeneration of salamanders tail a polygenic trait?

Yes. Many genes function to restore a lost tail.

If you were to find those genes how would you incorporate into human genomes?

We estimate that 90% of salamander genes have homologs in the human genome.....what this means is that if we could go back in time and find the common ancestor of modern salamanders and the amniote lineage (mammals and reptiles) leading to humans, that ancestor had these 90% of genes. So human regeneration will probably require more than putting salamander genes into the human genome. What we can learn from salamanders is how the functions of genes have changed to allow for regeneration, and how these genes, and perhaps a few novel genes, can be manipulated in human cells.

How do the regenerative properties of salamanders apply to medical uses?

In addition to the last sentence above, we are interested in identifying the mechanisms that salamanders use to rapidly close wounds and how they modify the wound environment to make it conducive for regeneration instead of scarring. We think salamanders regulate the expression of their genes differently than humans. For example, during wound healing, salamanders express some genes in the wound environment that are typically expressed in other tissues in humans, and not during wound healing. Manipulating the expression of the human homologs of salamander wound healing genes may increase the potential for regeneration. At the very least, it may lead to new products that better facilitate healing.