Evidence against natural selection and random mutations:
(a little more scientific than comparing apples to oranges because they are both round.)
Non-Random Mutation Explains Gene Region Patterns
In biological evolution, mutations provide the raw material for evolutionary change by introducing slight genetic variation among individuals. Today's standard thinking is that mutations occur at random and are then acted upon by the process of natural selection.
Natural selection, in turn, weeds out individuals with harmful mutations and favors those with beneficial mutations. But do all mutations actually occur at random? And does natural selection act on all mutations? To both questions, Howard Ochman of The University of Arizona in Tucson says no.
Ochman's research suggests that, at the molecular level, mutations may sometimes occur non-randomly. And it's generally believed that the vast majority of our DNA is non-functional and therefore not subject to natural selection.
In a report in the July 1 issue of Nature, Ochman and graduate student M. Pilar Francino set out to resolve a longstanding debate by showing that non-random mutation, rather than selection, can explain intriguing patterns among gene regions called "isochores" found in the genomes of mammals.
Francino is a doctoral student at the University of Rochester, which Ochman recently left to join UA in Tucson, where he is an associate professor in the ecology and evolutionary biology department.
An isochore is a region of the chromosome that shows a markedly different base composition than surrounding regions. Chromosomes consist of DNA, which in turn is made up of strings of nucleotides, or "bases" -- small molecules that come in four varieties (abbreviated as G, A, T, and C, after the first letters of their names).
Pairs of these bases are strung together like links in a chain, forming the long DNA molecule that encodes genetic information that is passed from one generation to the next.
The rare events called mutations occur when one type of nucleotide is replaced by another -- a C replaced by a T, say, or an A by a G. But although any given gene may include hundreds or thousands of bases, the Gs, As, Ts, and Cs aren't necessarily evenly distributed. Instead, some stretches of DNA contain more than their fair share of Gs and Cs, while others include an overabundance of As and Ts.
When one observes such differences between regions -- as between isochores -- is it because natural selection favors such a pattern, or is it due to non-selective causes such as a bias in mutation rates?
Questions like these are central to the rapidly-growing field of molecular evolution, in which the flowering of techniques in molecular biology in the past few decades has allowed biologists to take questions traditionally asked at the level of the organism and pose them at the level of the gene.
Determining under what conditions natural selection does and does not play a role in driving change at the molecular level has been one of the most prominent issues in molecular evolution.
Are isochores the result of biased mutation or of random mutation followed by selection? While many American and Japanese scientists have favored the mutational bias explanation, Ochman says, some Europeans have insistently pushed the selective argument.
To address this issue, Francino and Ochman worked with non-functional copies of the globin genes of primates. Using these "pseudogenes" assures that natural selection is not constraining which mutations are allowed to persist; all mutations are accepted and may be able to accumulate in the population.
Globin genes code for molecules (such our blood's hemoglobin) that are able to transport oxygen. In the history of mammals, the ancestral globin gene has duplicated a number of times, leaving clusters of genes, including the pseudogenes, some of which fall within different isochores.
Francino and Ochman selected two pseudogenes located on different chromosomes and in different isochores. One isochore had a preponderance of Gs and Cs, while the other was overstocked with As and Ts.
By analyzing the patterns of mutation in the two pseudogenes, the scientists tried to determine whether mutations of different types were occurring at different rates in the two isochores, or whether the four nucleotides were appearing in both regions with equal probability, but natural selection was favoring Gs and Cs in one region and As and Ts in the other.
Scientists can't just watch mutations happen, especially when the average primate nucleotide only mutates once per 400 million years.
"Since it's tough to do this in real time," Ochman understates, "we take a phylogenetic approach," meaning the history of nucleotide changes is inferred by using an evolutionary history of primate species and their ancestors.
First Francino and Ochman used gene sequences from humans and a variety of apes and monkeys in combination with a genealogy of primate evolution to reconstruct likely gene sequences of ancestral primates. They then used this information to infer the changes that had occurred in the nucleotide sequences throughout the evolutionary history of primates.
The data showed that a bias in mutations -- rather than the process of selection -- was responsible for the difference between isochores.
"This helps tell us how mutations occur in the genome," Ochman says. "It tells us about the factors that mold the human genome, and whether they're due to differential mutations or selective pressures."
Why are there differences in base composition in different areas of the genome? Ochman doesn't know, nor does anyone else -- yet. A number of reasons have been proposed, and Francino and Ochman suggest several in their paper in Nature.
[Contact: Howard Ochman]
07-Jul-1999
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