Saturday, March 28, 2009

Human mutation rate associated with DNA replication timing, by Stamatoyannopoulos

Human mutation rate associated with DNA replication timing, Nature Genetics, 41: 393-395, 2009
Abstract:
Eukaryotic DNA replication is highly stratified, with different genomic regions shown to replicate at characteristic times during S phase. Here we observe that mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome. All classes of substitutions are affected, suggesting a generalized mechanism involving replication time-dependent DNA damage. This correlation between mutation rate and regionally stratified replication timing may have substantial evolutionary implications.


This paper supports the maximum genetic diversity (MGD) hypothesis. Late replicating DNAs are in heterochromatin state and are enriched with non-coding sequences. They are under less functional constraint than euchromatins and are expected to show higher maximum genetic diversity. So, in fact, mutation rate has little to do with the result reported in this paper.

Tuesday, March 24, 2009

Meat intake and mortality, by Sinha et al

A large study on meat and mortality was published today (Arch Intern Med, 2009, 169: 562-571.) The paper concludes that "Red and processed meat intakes were associated with modest increases in total mortality, cancer mortality, and cardiovascular disease mortality." But my careful review of the paper suggests that it is total meat intake rather than color that is important, consistent with my earlier observations on other similar studies.

I sent the following email to the corresponding author:

Dear Dr. Sinha,

I read with great interest your article "meat intake and mortality". I work on epigenetics and the role of diet in cancer. My latest paper here:
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003390

From Table 1 of your paper, it is shown that the group (Q5) with the highest red meat intake consumed 119 g/kcal of all meat combined. Can you share the data of total amount of all meat about the group with the highest white meat intake? My estimation based on your reported data for this group is 69 g/kcal.

So, it seems that people who mostly eat white meat consumed about 2 fold less total meat than people who eat red meat.

People with highest intake of white meat have lower risk of death than those with lowest intake, as you reported. But those with low intake of white meat actually consume more red meat and total meat in general (table 1).

Bottom line, your data overall shows a link between total amount of meat and mortality. The color of meat is irrelevant. I have made this observation before on the original papers by Willett linking red meat with colon cancer. see my book chapter in Cancer Epigenetics: http://www.amazon.com/Cancer-Epigenetics-Trygve-Tollefsbol/dp/1420045792/ref=sr_1_1?ie=UTF8&s=books&qid=1226425804&sr=1-1

I wish that you could make a follow up revision and change the conclusion "Red and processed meat intakes were associated with modest increases in total mortality, cancer mortality, and cardiovascular disease mortality." to "Higher meat intake were associated with modest increases in total mortality, cancer mortality, and cardiovascular disease mortality."

Sincerely yours,

Shi Huang

Sunday, March 15, 2009

The mode and tempo of genome size evolution in eukaryotes

This old paper from 2007 was just brought to my attention by a netter discussing the MGD and the latest Science paper on high mutation rate of small genomes. This 2007 paper shows that large genomes show higher rate of large DNA segment duplications, insertions, rearrangments, etc, so called high rate of genome evolution in large genomes. These events are in fact both genetic and epigenetic, and are in fact stated in my MGD paper as epigenetic. Inserting a gene encoding an epigenetic enzyme is more of an epigenetic event. So, large genomes mainly use DNA indels and rearrangements, rather than point mutations, to adapt and evolve. This is the opposite of small genomes or simple organisms. This is entirely predicted by the MGD that large genomes or complex organisms use mainly epigenetic mechanisms rather than point mutations to evolve. Genetic diversity defined in the MGD paper is about neutral point mutations (some neutral indels may be included as well).


The mode and tempo of genome size evolution in eukaryotes
Matthew J. Oliver1,5, Dmitri Petrov2, David Ackerly3, Paul Falkowski1,4, and Oscar M. Schofield1
+Author Affiliations

1 Institute of Marine and Coastal Sciences, Rutgers University, New Brunswick, New Jersey 08901, USA;
2 Department of Biology, Stanford University, Stanford, California 93405, USA;
3 Department of Integrative Biology, University of California Berkeley, Berkeley, California 94720, USA;
4 Department of Geological Sciences, Rutgers University, Piscataway, New Jersey 08854, USA

Abstract

Eukaryotic genome size varies over five orders of magnitude; however, the distribution is strongly skewed toward small values. Genome size is highly correlated to a number of phenotypic traits, suggesting that the relative lack of large genomes in eukaryotes is due to selective removal. Using phylogenetic contrasts, we show that the rate of genome size evolution is proportional to genome size, with the fastest rates occurring in the largest genomes. This trend is evident across the 20 major eukaryotic clades analyzed, indicating that over long time scales, proportional change is the dominant and universal mode of genome-size evolution in eukaryotes. Our results reveal that the evolution of eukaryotic genome size can be described by a simple proportional model of evolution. This model explains the skewed distribution of eukaryotic genome sizes without invoking strong selection against large genomes.

Friday, March 6, 2009

Extremely High Mutation Rate of a Hammerhead Viroid by Gago et al

This Science paper confirms the MGD hypothesis. The author stated: "Such error-prone replication can only be tolerated by extremely simple genomes such as those of viroids." The simpler the organism, the more mutations it can tolerate.

Science 6 March 2009:
Vol. 323. no. 5919, p. 1308
DOI: 10.1126/science.1169202 Prev | Table of Contents | Next
BREVIA
Extremely High Mutation Rate of a Hammerhead Viroid
Selma Gago,1 Santiago F. Elena,1 Ricardo Flores,1 Rafael Sanjuán1,2*
The mutation rates of viroids, plant pathogens with minimal non-protein-coding RNA genomes, are unknown. Their replication is mediated by host RNA polymerases and, in some cases, by hammerhead ribozymes, small self-cleaving motifs embedded in the viroid. By using the principle that the population frequency of nonviable genotypes equals the mutation rate, we screened for changes that inactivated the hammerheads of Chrysanthemum chlorotic mottle viroid. We obtained a mutation rate of 1/400 per site, the highest reported for any biological entity. Such error-prone replication can only be tolerated by extremely simple genomes such as those of viroids and, presumably, the primitive replicons of the RNA world. Our results suggest that the emergence of replication fidelity was critical for the evolution of complexity in the early history of life.

Also see this Science comment: "Fast-Mutating Viroids Hold Clues to Early Life" by Carl Zimmer
http://blogs.sciencemag.org/origins/2009/03/fast-mutating-viroids-hold-clu.html

"What's intriguing about this pattern is the size of the genomes involved: The higher the mutation rate, the smaller the genome."