Offices Adopt Safety Protocols Meant for the Field – WSJ

July 29, 2014

In pursuit of design principles of regulatory sequences – Nat Rev Genet

July 29, 2014

In pursuit of design principles of regulatory sequences

Michal Levo & Eran Segal

Nature Reviews Genetics 15, 453–468 (2014) doi:10.1038/nrg3684

Ecker mentions: Design principles of regulatory sequences … for schematics on how to follow up reg. variants #GSPfuture

Common Fund for 4D Nucleome Study

July 29, 2014

One of a Kind – New Yorker

July 29, 2014

Medical Dispatch JULY 21, 2014 ISSUE
One of a Kind
What do you do if your child has a condition that is new to science?

Loss-of-function mutations in SLC30A8 protect against type 2 diabetes

July 29, 2014

Lots of LOF! — Boenke mentions: LOF mutations in SLC30A8 protect against T2D Power of combining data for mult. variants #GSPfuture

Can Reddit Grow Up? –

July 29, 2014

Ivy League Power Propels Columbia’s Tim Wu in Bid to be New York’s Lieutenant Governor – WSJ

July 28, 2014

The significance of the 2013 Nobel Prize in… PLoS Comput Biol. 2014 – PubMed – NCBI

July 24, 2014

New York Yankees on the Forbes MLB Team Valuations List

July 23, 2014

New York Yankees

Team Value: $2,500 M
Team Value calculated March 2014

At a Glance

Owner: Steinbrenner Family
Championships: 27
Price Paid: $10 M
Year Purchased: 1973
Revenue : $461 M
Operating Income : $-9.1 M
Debt/Value : 1%
Player Expenses : $225 M

Evolution at Two Levels: On Genes and Form

July 23, 2014

Evolution at 2 Levels: Genes &
Form Reg evol likely for genes in mult tissues, w. pleiotropic coding SNPs & mult CRMs


One critical parameter that affects the relative contribution of different genetic mechanisms to anatomical variation is the pleiotropy of mutations []. In general, it is expected that mutations with greater pleiotropic effects will have more deleterious effects on organismal fitness and will be a less common source of variation in form than mutations with less widespread effects.

Over the past 30 years, several key features of gene structure, function, and regulation in multicellular organisms have emerged that govern the pleiotropy of mutations and thus shape the capacity of species to generate anatomical variation and to evolve (see ). Because of these features, mutations in different genes and different parts of genes (that is, non-coding and coding sequences) can differ
dramatically in their degree of pleiotropy. For example, a mutation in the coding region of a transcription factor that functions in multiple tissues may directly affect all of the genes the protein regulates. In contrast, a mutation in a single cis-regulatory element will affect gene expression only in the domain governed by that element.

The most influential single publication of this era, however, was Susumu Ohno’s book Evolution by Gene Duplication []. Ohno focused on the importance of gene redundancy in allowing “forbidden” mutations to occur that could impart new functions to proteins. His opening motto, “natural selection merely modified, while redundancy created,” reflected a view of natural selection as a largely purifying, conservative process. Ohno insisted that “allelic mutations of already existing gene loci cannot account for major changes in evolution.”

…the estimated rate of gene duplication is about once per gene per 100 million years []. This figure suggests that gene duplication can contribute to genome evolution over longer spans of evolutionary time (for example, greater than 50 million years)….

The human FOXP2 gene encodes a transcription factor, and mutations at the locus were discovered to be associated with a speech and language disorder…. While it would certainly be convenient if the two changes in the FOXP2 protein were functional, the additional hypothesis must be considered that functional regulatory changes might have occurred at theFOXP2 locus. In weighing alternative hypotheses of FOXP2 or any gene’s potential involvement in the evolution of form (or neural circuitry), we should ask the following questions. (i) Is the gene product used in multiple tissues? (ii) Are mutations in the coding sequence known or likely to be pleiotropic? (iii) Does the locus contain multiple cis-regulatory elements?

If the answers are yes to all of these questions, then regulatory sequence evolution is the more likely mode of evolution than coding sequence evolution.



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