Debunking myths on genetics and DNA

Monday, December 10, 2012

Whole genome harvesting

You think the human genome, with its three billion base pairs and 23 chromosome pairs, is too complex to unravel? Turns out, the wheat genome is six times as big and it's hexaploid, in other words, instead of chromosome pairs it's organized in chromosome sextets!

I've recently discussed genetically modified organisms, crops in particular, and while I still can't provide a definite answer on whether they are absolutely good or absolutely bad, one thing struck me as relevant as I was researching the topic: between climate changes and an exponentially growing population, we are making drastic changes to our planet and resources. While Mother Nature is usually able to buffer changes and constantly adapt to new environments, the changes human kind is bringing upon the planet are happening at such a fast rate that natural adaptation is unable to keep up.

I think at some point we will have to face a hard choice: either starve or give in to GMOs, where by GMOs I mean crops that are bioengineered to yield more in harsher conditions. Again, I'm not saying we should all embrace GMOs as they are healthy and good for us. I really don't know. What I'm saying is that we may not have a choice: in 2009 the FAO estimated that in order to meet the ever-growing demand, wheat production has to increase by 60% by 2050. In the 20th century, the Green Revolution met the increase in demand with the technology known at the time. Today, given the FAO estimate, we may face the need of a second Green Revolution.

With this in mind, you understand the importance of sequencing the wheat genome, a task that is complicated by the complexity of the genome itself. Its three sets of chromosome pairs originated first from the hybridization of two diploid wild grasses, which originated tetraploid wheats (two sets of chromosome pairs) like durum wheat. After thousand years of domestications, these underwent a further hybridization, yielding the hexaploid wheats commonly used today to make bread. Domestication led to a bottleneck in genome variety, nonetheless, the wheat genome has a high percentage of repeats (roughly 80%, mostly retroelements) that yield great variation in length and gene order, making it difficult to sequence.

Despite these obstacles, two papers [1,2] in the latest issue of Nature report using both whole-genome 454 sequencing and shotgun sequencing to assemble the genome of bread wheat and barley. Both sequencing methods have the shortcoming of being applicable to very short regions, and therefore additional work is required to reassemble the full genome out of the various short sequences.

Interestingly, the wheat genome appears to implement a lot of the variation mechanisms I've been extensively discussing here on the blog:
"Several classes of plant DNA transposons and retroelements create and amplify gene fragments, disrupt genes and create pseudogenes, which can influence gene expression through epigenetic mechanisms [1]."
Similarly, in barley:
"Abundant alternative splicing, premature termination codons and novel transcriptionally active regions suggest that post-transcriptional processing forms an important regulatory layer. Survey sequences from diverse accessions reveal a landscape of extensive single-nucleotide variation [2]."
Brenchley et al. [1] conclude:
"Major efforts are underway to improve wheat productivity by increasing genetic diversity in breeding materials and through genetic analysis of traits43. The genomic resources that we have developed promise to accelerate progress by facilitating the identification of useful variation in genes of wheat landraces and progenitor species, and by providing genomic landmarks to guide progeny selection. Analysis of complex polygenic traits such as yield and nutrient use efficiency will also be accelerated, contributing to sustainable increases in wheat crop production [1]."

[1] Brenchley, R., Spannagl, M., Pfeifer, M., Barker, G., D’Amore, R., Allen, A., McKenzie, N., Kramer, M., Kerhornou, A., Bolser, D., Kay, S., Waite, D., Trick, M., Bancroft, I., Gu, Y., Huo, N., Luo, M., Sehgal, S., et al. (2012). Analysis of the bread wheat genome using whole-genome shotgun sequencing Nature, 491 (7426), 705-710 DOI: 10.1038/nature11650

[2] Mayer, K., Waugh, R., Langridge, P., Close, T., Wise, R., Graner, A., Matsumoto, T., Sato, K., Schulman, A., et al. (2012). A physical, genetic and functional sequence assembly of the barley genome Nature DOI: 10.1038/nature11543

Friday, December 7, 2012

The simulated brain

His name is Spaun, which stands for Semantic Pointer Architecture Unified Network, and he's a brain -- a simulated, brain. His 2.5 million neurons, organized in subsystems that simulate different brain areas, allow Spaun to perform tasks such as image recognition and recalling sequences, and respond through a motor arm. For example, Spaun can recognize numbers on a screen and write them on a piece of paper.

Spaun is the brain child (pun intended!) of authors Eliasmith et al. [1]. It models three specific brain areas: the prefrontal cortex for memory, the basal ganglia to select actions, and the thalamus. Spaun's functional architecture consists of a working memory that, given a visual input, compresses the information and translates the input into firing patterns. The next step is the action selection step, which results in a motor output through the robotic arm. Spaun's memory doesn't just store information, but it also correlates new information with the old one. A nice feature of the model is that different neuron parameters can be chosen from random distributions in order to simulate different population behaviors. This simulates the human brain so well that Spaun expresses a common human behavior: the tendency to remember best the first and last items in a list.

On the other hand, Spaun exhibits noteworthy deviations from human brains: while it can get better and better at a particular task, it cannot learn a completely new task. Another shortcoming is that Spaun's attention and eye position are fixed, so that, contrary to a real human brain, it cannot control the input.

As the authors explain:
"Anatomically, many areas of the brain are missing from the model. Those that are included have too few neurons and perform only a subset of functions found in their respective areas. Physiologically, the variability of spiking in the model is not always reflective of the variability observed in real brains. However, we believe that, as available computa- tional power increases, many of these limitations can be overcome via the same methods as those used to construct Spaun."

[1] Eliasmith, C., Stewart, T., Choo, X., Bekolay, T., DeWolf, T., Tang, Y., & Rasmussen, D. (2012). A Large-Scale Model of the Functioning Brain Science, 338 (6111), 1202-1205 DOI: 10.1126/science.1225266

Tuesday, December 4, 2012

Make a donation to NOAH, get a free 8x12 print

As many of you know, my research is on HIV, with a focus on HIV vaccine design. I work in Bette Korber's group, and through Bette, I came to learn about NOAH, an organization she co-founded.

Taking care of AIDS orphans has been one of the most prominent issues in Sub-Saharan Africa, where two-thirds of the people affected by HIV/AIDS live. Mother-to-infant transmissions are highly preventable yet, sadly, the drugs are expensive and not always available in Africa. A staggering 2.5 million African children have been orphaned by AIDS, and many of them are born HIV-positive. There are villages where a whole generation has disappeared because of AIDS.

NOAH takes care of these children without taking them away from their homes. NOAH is not an orphanage. The organization provides schooling, day care and food for the kids, while the kids continue to live in their village with older relatives. $80 covers one child for one year.

For the whole month of December, if you make a donation of $30 or more, I will send you an 8x12 print of one of my pictures. Follow this link to donate, forward the email receipt to eegiorgi (at), include your shipping address, and pick the picture of your choice from my G+ album (click on "Photo details" to see the file name).

Donations are tax-deductible.