Genetics “Central Dogma” Is Dead

“The gene is dead... long live the gene,” announced subtitles to an article in Science News this week.1 Geneticists have come to a striking conclusion over the last few years: genes are not the most important things in DNA, if they even exist as a concept.

The “central dogma” of genetics, since Watson and Crick determined the structure of DNA, is that genetic information flows one-way – from the gene to the protein. In the textbooks, a gene was supposed to be a finite stretch of DNA that, when read by the translation process, produced a messenger RNA, which recruited transfer RNAs to assemble the amino acids for one protein.

As Patrick Barry described in his article “Genome 2.0,”1 the situation in real cells is much messier. “Mountains of new data are challenging old views,” his subtitle announced, including the “modern orthodoxy” that only genes are important:

"Researchers slowly realized, however, that genes occupy only about 1.5 percent of the genome. The other 98.5 percent, dubbed “junk DNA,“ was regarded as useless scraps left over from billions of years of random genetic mutations. As geneticists’ knowledge progressed, this basic picture remained largely unquestioned...." "Closer examination of the full human genome is now causing scientists to return to some questions they thought they had settled. For one, they’re revisiting the very notion of what a gene is."...

Nice picture, but what does it mean? Is it trying to show splicing? The data of RNA transcripts coded for by DNA on different regions or even different chromosomes possibly being essential for a specific gene to function is poorly represented by the picture of jumping arrows.

The classic view is that a gene makes a RNA transcript that gets made into a protein.

The view in light of the data is that a gene makes a RNA transcript that possibly needs other nonproteincoding RNA to be made into a protein.

What do the jumping arrows mean?

What fundamental misunderstanding of the information contained in DNA?

The information codes for protein in genes and that is what the Central Dogma is all about, how the information to make all the proteins that make the cell work is contained. It is in the sequence to sequence matching of DNA to Amino Acid.

There is also specific functionality in RNA transcripts coded for by DNA. This is not a contradiction of the Central Dogma. It happens in DNA repair, DNA replication, and Protein Translation. RNA is highly functional stuff and does more than just code for proteins. That is mRNA has a ‘m’for messenger; because there is also tRNA and rRNA and maybe some others we do not know about yet.

This is the information contained in the DNA code for an Amino Acid Sequence to make a protein that performs a function in the cell (structural, enzymatic, signaling, etc). This is what the Central Dogma is all about, that the information is in DNA, and that through RNA it specifies a specific amino acid sequence.

This table shows the 64 codons and the amino acid each codon codes for. The direction is 5’ to 3’. 2nd base
U C A G
1st
base U UUU (Phe/F)Phenylalanine
UUC (Phe/F)Phenylalanine
UUA (Leu/L)Leucine
UUG (Leu/L)Leucine

UCU (Ser/S)Serine
UCC (Ser/S)Serine
UCA (Ser/S)Serine
UCG (Ser/S)Serine

UAU (Tyr/Y)Tyrosine
UAC (Tyr/Y)Tyrosine
UAA Ochre (Stop)
UAG Amber (Stop)

UGU (Cys/C)Cysteine
UGC (Cys/C)Cysteine
UGA Opal (Stop)
UGG (Trp/W)Tryptophan

C CUU (Leu/L)Leucine
CUC (Leu/L)Leucine
CUA (Leu/L)Leucine
CUG (Leu/L)Leucine

CCU (Pro/P)Proline
CCC (Pro/P)Proline
CCA (Pro/P)Proline
CCG (Pro/P)Proline

CAU (His/H)Histidine
CAC (His/H)Histidine
CAA (Gln/Q)Glutamine
CAG (Gln/Q)Glutamine

CGU (Arg/R)Arginine
CGC (Arg/R)Arginine
CGA (Arg/R)Arginine
CGG (Arg/R)Arginine

A AUU (Ile/I)Isoleucine
AUC (Ile/I)Isoleucine
AUA (Ile/I)Isoleucine
AUG (Met/M)Methionine, Start[1]

ACU (Thr/T)Threonine
ACC (Thr/T)Threonine
ACA (Thr/T)Threonine
ACG (Thr/T)Threonine

AAU (Asn/N)Asparagine
AAC (Asn/N)Asparagine
AAA (Lys/K)Lysine
AAG (Lys/K)Lysine

AGU (Ser/S)Serine
AGC (Ser/S)Serine
AGA (Arg/R)Arginine
AGG (Arg/R)Arginine

G GUU (Val/V)Valine
GUC (Val/V)Valine
GUA (Val/V)Valine
GUG (Val/V)Valine

GCU (Ala/A)Alanine
GCC (Ala/A)Alanine
GCA (Ala/A)Alanine
GCG (Ala/A)Alanine

GAU (Asp/D)Aspartic acid
GAC (Asp/D)Aspartic acid
GAA (Glu/E)Glutamic acid
GAG (Glu/E)Glutamic acid

GGU (Gly/G)Glycine
GGC (Gly/G)Glycine
GGA (Gly/G)Glycine
GGG (Gly/G)Glycine

You forgot the caption to the picture....

TANGLED GENES. In the classic view of the genome (top), individual genes were distinct segments of DNA that a cell transcribed into RNA whole and in one direction. New data show that multiple and overlapping genes can occupy a single strip of DNA that also produces several functional RNAs that don’t encode proteins (bottom, not to scale).
S. Norcross

BOTTOM NOT TO SCALE

In the old view, each gene sat in splendid isolation on its segment of the genome. Other genes might be nearby, but scientists assumed that they didn’t overlap each other.

Now it’s clear that a single length of DNA can be transcribed in multiple ways to produce many different RNAs, some coding for proteins and others constituting regulatory RNAs. By starting and stopping in different places, the transcription machinery can generate a regulatory RNA from a length of DNA that overlaps a protein-coding gene. Moreover, the code for another regulatory RNA might run in the opposite direction on the facing strand of DNA. According to the ENCODE project results, up to 72 percent of known genes have transcripts on the facing DNA strand as well as the main strand.

http://www.sciencenews.org/articles/20070908/bob9.asp

Information is still the Universal Code of DNA triplet to Amino Acid in sequence by sequence.

Information is still the Universal Code of DNA triplet to Amino Acid in sequence by sequence.

Okay, so now you have updated the Central Dogma from DNA->RNA->Protein to DNA->RNA->Amino Acid. This works, but it is a modified definition that has to account for the information encoding for a protein spread out and overlapping on multiple chromosomes. The point is not that the basic Central Dogma Definition on its surface is wrong, but the assumptions Crick depends upon to arrive at the Central Dogma have crumbled to the point of needing to redefine basic genetics like what a "protein encoding gene" is, or if it exists as anything more than an abstract concept.

BTW, thanks for referring to the article in question I had the feeling we were discussing something else for a while.

A protein is made up of a sequence of Amino Acids so there is no difference between DNA->RNA->Protein and DNA->RNA->Amino Acid.

Not all genes for a protein are spread out over overlapping and multiple chromosomes.

The assumptions of Crick still stand. The Central Dogma has been validated and is not crumbling.

The concept of what a protein coding gene is has become more complex, but it is STILL EXACTLY what Crick said it was; information in nucleic acid that specifies an Amino Acid. It is not an abstract concept, it is a REAL phenomenon, it is just not as simple in complex animals as it is in bacteria because of splicing (possibly from distal sequences even on different chromosomes) and the possible intervention of regulatory RNA.

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