Post details: Beyond Genes and the Central Dogma

09/14/07

Permalinkby 07:48:40 am, Categories: Literature - Articles, 1067 words   English (UK)

Beyond Genes and the Central Dogma

It is interesting to find a biological article referring to "mountains of data" challenging "old views" that is not concerned with the supposed "mountains of evidence" against the concept of design in nature! In this case, the focus is on genes: "Only 6 years later, the landscape of the genome is already proving to be dramatically different than most scientists had expected."
The trigger for the new views has been a project called the Encyclopedia of DNA Elements (ENCODE), previously noted here for contributing to the overthrow of the Junk DNA paradigm. Barry: "Even more surprisingly, the junk DNA may not be junk after all. Most of this supposedly useless DNA now appears to produce transcriptions of its genetic code, boosting the raw information output of the genome to about 62 times what genes alone would produce."
However, this is only part of the challenge to the "old views". There is a need for some radical thinking about genes themselves. Barry summarises the situation in his useful online article. An academic paper developing these new ideas is by Gingeras. He writes: "studies focused on noncoding transcripts of known biological function have begun to reveal a complexity in genome organization not captured by the current collection of annotations, prompting a reconsideration of what constitutes the fundamental functional element of the genome and how it relates to phenotypic variation." He argues the case for the definition of a new operational unit which will supersede the gene in our thinking. "If each of the transcripts sharing sequence space with a protein-coding gene are capable of effecting the same phenotype/function, then a gene can consist of multiple (coding and noncoding) transcripts and regulatory regions (Fig. 1D). This increased complexity of both the components of a gene and its boundaries begs for a simpler operational unit that can be used to link a specific DNA sequence to phenotype/function. Individual RNA transcripts provide these fundamental operational elements."
Whilst this conclusion appears eminently justified by the evidence, there are dramatic implications for evolutionary theory, which has so often been developed using concepts that are now out-of-date. We have to discard not only Junk DNA, but also the "Central Dogma", the "selfish gene" and the conceptual model of characters controlled by single genes and under the influence of natural selection forces. Barry puts his finger on a significant challenge this brings to neoDarwinian evolutionary theory:

"The same sequences are being used for multiple functions," says Thomas R. Gingeras of Affymetrix. That introduces complications into the evolution of the genome, which had until recently been assumed to act through single DNA mutations affecting single genes. Now, "a mutation in one of those sequences has to be interpreted not only in terms of [one gene], but [of] all the other transcripts going through the region," Gingeras explains.
The implications of this single mutation-multiple consequence model are still a matter of debate. In some cases, the RNA transcripts from DNA that overlaps a protein-coding gene regulate that same gene, so a mutation could affect both the structure and the regulation of a protein. But often, those transcripts regulate genes that are far away, or even on different chromosomes. This complex interweaving of genes, transcripts, and regulation makes the net effect of a single mutation on an organism much more difficult to predict, Gingeras says.

Nickerson has some significant comments on the significance of these findings:

The discoveries have one common theme: Cellular processes long assumed to be "genetic" appear quite often to be the result of highly complex interactions occurring in regions of DNA void of genes. This is roughly akin to Wall Street waking to the realization that money doesn't make the world go 'round, after all.
"It's a radical concept, one that a lot of scientists aren't very happy with," said Francis S. Collins, director of the National Human Genome Research Institute. "But the scientific community is going to have to rethink what genes are, what they do and don't do, and how the genome's functional elements have evolved." "I think we're all pretty awed by what we're seeing," Collins said. "It amounts to a scientific revolution."

The complexity discovered has been difficult to describe. One researcher is quoted as saying: "The picture that's emerging [of how living cells actually operate and evolve] is so immensely more complicated than anyone imagined, it's almost depressing". Casual observers might say they find chaos in the emerging picture of the genome, but systems biology is tracking down extraordinary sophistication at the molecular biology level, indicating that theories (like Darwinism) that are undirected and stochastic have little to offer 21st Century biology.

Genome 2.0 - Mountains of new data are challenging old views
Patrick Barry
Science News, September 8, 2007; 172(10), p. 154

First para: When scientists unveiled a draft of the human genome in early 2001, many cautioned that sequencing the genome was only the beginning. The long list of the four chemical components that make up all the strands of human DNA would not be a finished book of life, but a road map of an undiscovered country that would take decades to explore. Only 6 years later, the landscape of the genome is already proving to be dramatically different than most scientists had expected.

Origin of phenotypes: Genes and transcripts
Thomas R. Gingeras
Genome Research, 2007 17: 682-690. [Open Access]

Abstract: While the concept of a gene has been helpful in defining the relationship of a portion of a genome to a phenotype, this traditional term may not be as useful as it once was. Currently, "gene" has come to refer principally to a genomic region producing a polyadenylated mRNA that encodes a protein. However, the recent emergence of a large collection of unannotated transcripts with apparently little protein coding capacity, collectively called transcripts of unknown function (TUFs), has begun to blur the physical boundaries and genomic organization of genic regions with noncoding transcripts often overlapping protein-coding genes on the same (sense) and opposite strand (antisense). Moreover, they are often located in intergenic regions, making the genic portions of the human genome an interleaved network of both annotated polyadenylated and nonpolyadenylated transcripts, including splice variants with novel 5' ends extending hundreds of kilobases. This complex transcriptional organization and other recently observed features of genomes argue for the reconsideration of the term "gene" and suggests that transcripts may be used to define the operational unit of a genome.

See also:

Nickerson, C. DNA unraveled, Boston Globe, September 24, 2007

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