Primatology.net

The orangutan genome has been sequenced and published in today’s Nature. The paper, “Comparative and demographic analysis of orang-utan genomes,” is open access for you to read for yourself. I’ll be highlighting some of the high points in this post. Devin Locke, a structural geneticist at Washington University School of Medicine in St. Louis, Missouri, headed the sequencing of six Sumatran and five Bornean orangutans. As you may know Pongo abelii, or the Sumatran orangutan, is a separate species from Bornean orangutans — Pongo pygmaeus.

One remarkable finding of the study is the estimated divergence between the Sumatran and Bornean species. The team calculated the two species diverged 400,000 years ago. We know that land bridge between Indonesia’s Sumatra and Borneo split at least 21,000 years ago but until now we’ve never known at what time the two speciated.

Compared to the two other great apes whose genomes have been sequenced, humans and chimps, the orangutan genome has changed much less. We’re still waiting on the gorilla genome to be finished. Oangutans originated some 12 million to 16 million years ago. Theoretically, orangutans have had more time to accumulate  genetic variation compared to humans and chimpanzees, which split into their own lineages 5 million to 6 million years ago. One would expect at least twice as much variation in the orangutan genome. However, in the study, a comparison of the three genomes shows that humans and chimpanzees have lost or gained new genes at twice the rate of orangutans.

Why’s that?

The paper explains that orangutan genomes have much fewer active retrotransposons than human and chimp genomes. Retrotransposons, or Alu elements, are essentially jumping genes, that replicate, and amplify then insert into different parts of the genome. The initial 2001 draft of the human genome reported that around 42% of the human genome is made up of retrotransposons. The authors of the orangutan paper illustrate that the human genome has ~5,000 Alu elements, whereas the orangutan genome has 250. This is significantly different. The authors write,

“Reduced Alu retroposition potentially limited the effect of a wide variety of repeat-driven mutational mechanisms in the orang-utan lineage that played a major role in restructuring other primate genomes.”

Personally, and this is my thinking here nothing the authors say — a common source of many human retrotransposons are to prehistoric viruses that integrated into our ancestral DNA. Viruses are communicable. Orangutans are the most solitary Great apes. I suspect they would have much less exposure to viruses because of their social structure, and thus much less chance of insertion of retrotransposon. Again, this is a hypothesis of mine, and I could be very wrong to think this.

Comparison of Orangutan to Great Ape Alu sequences

One last finding, I want to bring up was published in another paper released by the same team, but in the journal Genome Research. In the paper, “Incomplete lineage sorting patterns among human, chimpanzee and orangutan suggest recent orangutan speciation and widespread selection,” coauthors of the previous study write that there are many similarities to the human and orangutan genome, much more similar than human to chimp, in fact. They suspect that could be because humans split from a common ancestor with chimps, of which both species had the same ancestral orangutan DNA. What remains curious is that humans and chimpanzees have evolved separately for millions of years. In the process, chimps for mysterious reasons lost some orangutan DNA that humans retained.

As often in sciences, many more questions arise from studies like these but I am excited that the age of genomics is shedding more light on our fellow primates!

Locke, D., Hillier, L., Warren, W., Worley, K., Nazareth, L., Muzny, D., Yang, S., Wang, Z., Chinwalla, A., Minx, P., Mitreva, M., Cook, L., Delehaunty, K., Fronick, C., Schmidt, H., Fulton, L., Fulton, R., Nelson, J., Magrini, V., Pohl, C., Graves, T., Markovic, C., Cree, A., Dinh, H., Hume, J., Kovar, C., Fowler, G., Lunter, G., Meader, S., Heger, A., Ponting, C., Marques-Bonet, T., Alkan, C., Chen, L., Cheng, Z., Kidd, J., Eichler, E., White, S., Searle, S., Vilella, A., Chen, Y., Flicek, P., Ma, J., Raney, B., Suh, B., Burhans, R., Herrero, J., Haussler, D., Faria, R., Fernando, O., Darré, F., Farré, D., Gazave, E., Oliva, M., Navarro, A., Roberto, R., Capozzi, O., Archidiacono, N., Valle, G., Purgato, S., Rocchi, M., Konkel, M., Walker, J., Ullmer, B., Batzer, M., Smit, A., Hubley, R., Casola, C., Schrider, D., Hahn, M., Quesada, V., Puente, X., Ordoñez, G., López-Otín, C., Vinar, T., Brejova, B., Ratan, A., Harris, R., Miller, W., Kosiol, C., Lawson, H., Taliwal, V., Martins, A., Siepel, A., RoyChoudhury, A., Ma, X., Degenhardt, J., Bustamante, C., Gutenkunst, R., Mailund, T., Dutheil, J., Hobolth, A., Schierup, M., Ryder, O., Yoshinaga, Y., de Jong, P., Weinstock, G., Rogers, J., Mardis, E., Gibbs, R., & Wilson, R. (2011). Comparative and demographic analysis of orang-utan genomes Nature, 469 (7331), 529-533 DOI: 10.1038/nature09687

Hobolth, A., Dutheil, J., Hawks, J., Schierup, M., & Mailund, T. (2011). Incomplete lineage sorting patterns among human, chimpanzee and orangutan suggest recent orangutan speciation and widespread selection Genome Research DOI: 10.1101/gr.114751.110

Plasmodium falciparum infecting Red Blood Cells

Plasmodium falciparum is the protozoan parasite that causes malaria in humans and ultimately the death of 2-3 million people a year. If you didn’t know, malaria is one of the most common infectious diseases and an enormous public health problem. Only one other malaria causing protozoan, a sister species of the P. falciparum parasite, P. reichenowi, was known to cause malaria but infects only chimpanzees. That was until researchers based in Gabon and France began sampling pet chimpanzees.

The team collected blood from 19 wild-borne animals kept as pets by villagers in Gabon, 17 of them being chimps. They found out that infected by a Plasmodium parasite, but sequencing of the parasite’s whole mitochondrial genome showed that it wasn’t P. falciparum nor P. reichenowi. Rather, it was a new species more closely related to P. falciparum. They classified the new species as P. gaboni.

Phylogenetic relationships among Plasmodium species (including P. sp_K) and associated host groups.

They have published their findings in the open access journal PLoS Genetics, under the title, “A New Malaria Agent in African Hominids.” You maybe asking why this is relevant to primatology? Many are against studies that use primates like chimpanzees because of ethical reasons. In situations like this, chimpanzees already infected with the parasite are useful to sample and study to shed light on the genomic adaptations of P. falciparum to humans and thus help in the discovery of new potential drug targets.

Ollomo, B., Durand, P., Prugnolle, F., Douzery, E., Arnathau, C., Nkoghe, D., Leroy, E., & Renaud, F. (2009). A New Malaria Agent in African Hominids PLoS Pathogens, 5 (5) DOI: 10.1371/journal.ppat.1000446

Single nucleotide polymorphisms (SNPs) are 1 base pair differences in the genetic code when compared to same sequence from another individual. Many population geneticists who study human genetics compare and contrast SNPs between different populations to understand ancestry and genaology. A new database of non-human primate SNPs, MonkeySNP, has been recently released, and was announced in the journal Bioinformatics.

I don’t regularly announce such news, but I consider this a pretty significant tool for any researchers who are studying primate diversity. As you may know many primate species are severely endangered and any successful conservation effort requires an understanding of the genetic diversity of the surviving population. This database will help currate this genetic diversity.

But the database is rather limited right now. Only 827 SNPs are listed, and are only macaque SNPs. I’m hopeful that as the genes and genomes of more primates species and individuals are sequenced this database will grow. In the mean time, I suggest you bookmark this site and keep an eye on it.

S. Khouangsathiene, C. Pearson, S. Street, B. Ferguson, C. Dubay (2008). MonkeySNP: a web portal for non-human primate single nucleotide polymorphisms Bioinformatics, 24 (22), 2645-2646 DOI: 10.1093/bioinformatics/btn493

PNAS will soon publish a paper from Mike Bruford and colleagues who isolated DNA from gorilla hair and feces and ultimately came up with a conclusion that the modern genetic composition of gorilla populations varies across different parts of their current geographic range and that this variation may be tied to Ice Age climate change and river barriers.

If that doesn’t make much sense, let me explain how such a situation would create genetic differences. During climate change between ice ages, populations that were in higher latitudes, found themselves separated physically because ice barriers formed and then collapsed, ultimately this segregated populations from one another another. Likewise, in drier climates, the tropics expanded and contracted to create isolated pockets much like what is created ice barriers. Ultimately these physical entities separated populations from one another. Also the genetic differences between gorilla populations is explained, in part, by the distance gorillas need to travel around river barriers, since in common with other large primates, they cannot cross large rivers.

Bruford comments on how this current study of gorilla population genetics is a crucial consideration,

“given the current catastrophic decline of great apes throughout Central Africa, current climate change patterns and the need to develop strategies to protect remaining populations from extinction.”

It seems like the news hasn’t gobbled up this news as adamantly as it did the news of the bonobo reserve in the Congo, but it is nonetheless newsworthy and crucial to the study of bonobos. The Department of Evolutionary Anthropology at the Max Planck Institute put out a press release that they just acquired a second Genome Sequencer FLX (GS FLX) System from 454. Svante Pääbo, director of the department, plans to put this one to use in sequencing the bonobo genome.

I’ve seen two of these 454 devices in person, over at the JGI. These things are gnarly, and cost a lot of money. I was told that each time you wanna use one of the machines, the reagents alone cost thousands of dollars. I didn’t ask to see a purchase order or anything, but I believe them. These devices do big science, they sequence small fragments of DNA and help on constructing it and they do it well.

You maybe asking, “What good does a bonobo genome do for us? We got chimpanzee, macaque, human… and we’re getting Neandertal, gorilla, and gibbon!” Well exactly that, the more primate genomes we have the more information we can get when we compare the genomes to one another. For example, between the bonobo, chimp, Neandertal, and human genomes we can screen to see what genes are specific to modern humans and what genes are specific to chimpanzees. This is critical in understanding what makes us all different, since it is proposed we share so much together.

In related news, I’m happy to announce that the Sankuru Nature Reserve a 11,803 square miles will be created through a partnership involving American and Congolese conservation groups and government agencies to help preserve bonobos. Lots of press has covered this news, for example here’s the New York Times coverage. As you may know all great apes are severly threatened if not endangered.

I could swear that in the past I had covered news that the minute genetic and massive phenotypic differences between humans and chimpanzees are due to the alternative splicing. But I can’t seem to find the post at all… there maybe a slight chance I didn’t post about it but I’m pretty sure I did cause this is the kind of science that I love to gobble up. Oh well… I guess it all doesn’t really matter because University of Toronto researchers, Benjamin Blencowe and John Calarco, have discovered significant differences in the way genetic material of humans and chimpanzees are spliced to create proteins.

Here’s a very brief introduction into splicing… Splicing is a type of modification of a gene that happens after a sequence is transcribed. What actually happens is that introns of pre-messenger RNA (pre-mRNA) are removed and exons of it are joined. I remember exons as expressed sequences and introns as intervening sequences.

This process produces the mature messenger RNA (mRNA), which then undergoes translation and ultimately becomes a protein. In many cases, the splicing process can create a range of unique proteins by varying the exon composition of the same messenger RNA. This phenomenon is then called alternative splicing. The illustration to your right documents what’s happening.

Blencowe comments,

“It’s clear that humans are very different from chimpanzees on several levels, but we wanted to find out if it could be the splicing process that accounts for some of these fundamental differences. The surprising thing we found was that six to eight per cent of the alternative splicing events we looked at were showing differences, which is quite significant. And those genes that showed differences in splicing are associated with a range of important processes, including susceptibility to certain diseases.”

He and his team have published their findings in the Journal of Genes and Development. The paper, “Global analysis of alternative splicing differences between humans and chimpanzees” can be summarized in one sentences, alternative splicing process differs significantly between humans and chimpanzees and is one of the main reasons as to why humans and chimpanzees are so different phenotypically but so similar genetically.

I just stumbled upon a new-to-me primatology blog that I wanted to share with you. The blog, DNApes, comes from Mimi Arandjelovic, a graduate student at the Max Planck power house of anthropology and is chock full of good posts.

Mimi studies variation in male-transmitted Y-chromosome of gorillas, which is extremely important given that gorillas are on the verge of extinction. She does that thru sampling poop. That’s where the name DNApes comes from. It stands for for DNA Analysts of poop, excrement and scat. As you may know, understanding the genetic variation is useful information when dealing with small populations.

Be sure to bookmark the blog, and if you’re into having news delivered to you, subscribe to the RSS feed.

The following post is a departure from my usual reporting on an interesting primate related tidbit of research. I’ll be posting about how I have thought about how to study primate brain evolution research. These are just ideas I have brainstormed. It is very probable that people are doing this out in their respective labs but I’m not in the know of what’s totally current. I hope you are interested in what scope of primate brain evolution research I will be discussion… I’ll be mostly taking in a functional genomic and computational biology approach, but that’s not to say more objective sciences such as psychology can’t fit into this game plan.

To start off, understanding primate brain evolution, specifically the biological mechanisms by how the primate brains have been positively selected for by size involves two complementary aspects of research. One of it is to identify the genes involved in brain growth and development, as well as their expression patterns. This is wet lab work, a whole lot of tissue sampling, mRNA isolation, cDNA synthesis and RT-PCR amplification, gene quantification and qualification and ultimately sequencing. At this level, one would need to sample multiple samples of representative primates (that have their genomes sequenced) and different developmental stages and populations.

Once these key players can be identified, the functions of these genes need to be well understood. Of course making knockout monkeys will be a costly and time consuming endeavor full of ethical issues, so I imagine having knockout neuron cultures can help understand the function of these genes better when they aren’t expressed. That’s a bit hard, neurons are awfully fickle to grown in culture. Maybe reporter constructs? Also, other non-traditional research such as sequence homology to other known proteins can help isolate potential functions based on structure.

Now once these key developmental genes have been classified, their relative importance should be noted… or in other words, one needs to organize which genes are specific to all primates and which are specific to fewer primates. Do these genes correlate with the known lineage of primates? If a unique pattern can be extracted, this will make the second aspect of research much easier and conclusive. This is the computational biology approach, using computers, statistics, and other mathematical models to identify what genes were mutated the most to yield the most growth. What genes remained fairly consistent? Can we estimate ages of coalescence or divergence, are there unique mutations to populations or species of primates… ultimately can we begin to make a phylogenetic tree of these genes and their changes throughout evolutionary time?

As I currently laid it out, these two field complement each other and if anything one is dependent on the other. Currently, I know of computational studies that seem to search high and low to find genes that have been positively selected for in primates by scanning and comparing entire genomes. If a hit is found, the research then shifts backwards to estimate functions based on the sequence homology to other known genes and their functions. While that maybe a useful, quick and easy approach, it’s all sorts of wrong. It is wrong because it is the needle in the haystack method. I advise one first narrow down the list, by doing the functional genomic screens, which is arduous and tedious, but much more quantitative and thorough. That way, one can limit things down to candidate genes specific to a species, developmental stage, etc. The playing field will be much more narrow and the computations will be much more conclusive.

What do you think? Do I have it right, do I have it wrong? Not to be rubbing my ego, but I think I have a thorough plan here — one that would make the most killer dissertation ever. Do you know of any researchers doing it this way? If any one out there, who reads this blog, carries out primate brain evolution research please feel free to comment and discuss. I’m really curious to know if what I have been thinking is even right.

I’m posting this as I run out the door, so forgive me if it is a bit brief and incomplete in explanation… but I have to share this resource/paper with you because less than 1 month ago the Macaque genome draft was released, and this publication is the first application, I know, of the draft of the Macaque genome we read about.

It is a library of unique SNPs to Macaques. SNPs stand for Single Nucleotide Polymorphisms and are defined as inter-individual variations in the genetic code at the level of one nucleotide. They help determine population similarities and differences, as well as operate as genetic landmarks useful for recombination analysis and mapping. This project was made by,

‘pyrosequenc[ing] an animal from western China to maximize diversity when compared to the draft sequence from a rhesus macaque of Indian ancestry.’

It was also made using the 454 sequencing method, famous for its application in the Neandertal genome sequencing project.

Here’s a link to the open access publication, “MamuSNP: A Resource for Rhesus Macaque (Macaca mulatta) Genomics,” and in case you ever wanna compare SNPs here’s a link to the project’s website. Okay, I gotta run, bye!

So if you have been in the dark about what’s been making a lot of buzz around the internet today, have no worries. I’m more than happy to explain it to you, because this new research will really help us understand what it means to be human and non-human.

How, you ask?

Well, it identifies a unique protein in human brains and compares that to chimpanzees. This form of comparison is important. Often, I’ve told people that, while it maybe significant that chimpanzees and humans share a remarkable amount of genomic similarity, where we don’t share similarities, areas that span millions of base pairs, the developmental implications are really dramatic.

The research is hardcore molecular biology, specifically proteomics. Proteomics is a branch of molecular biology that seeks to determine the large scale patterns of protein expression and function. The researchers, led by Dr. Bing Su of the Chinese Academy of Sciences in Kunming, China, show,

“a certain form of neuropsin, a protein that plays a role in learning and memory, is expressed only in the central nervous systems of humans and that it originated less than 5 million years ago. The study, which also demonstrated the molecular mechanism that creates this novel protein.”

The publication, ain’t out yet. But I’m getting this all from EurekAlert, a very trustworthy pop-science news outlet run by Science. The divergence time of this protein falls in line with newly assessed dates of human lineage divergence from other great apes. So it has got that going for itself.

The specific paper will be published in Human Variation.

Su had an idea on where to look and what to compare, because her previous work had shown a longer form of the protein, neuropsin II,

“is not expressed in the prefrontal cortex (PFC) of lesser apes and Old World monkeys. In the current study, they tested the expression of type II in the PFC of two great ape species, chimpanzees and orangutans, and found that it was not present. Since these two species diverged most recently from human ancestors (about 5 and 14 million years ago respectively), this finding demonstrates that type II is a human-specific form that originated relatively recently, less than 5 million years ago.

Gene sequencing revealed a mutation specific to humans that triggers a change in the splicing pattern of the neuropsin gene, creating a new splicing site and a longer protein. Introducing this mutation into chimpanzee DNA resulted in the creation of type II neuropsin. “Hence, the human-specific mutation is not only necessary but also sufficient in creating the novel splice form,” the authors state.”

Human version of neuropsin is longer, which alters the efficacy of its function. I don’t know how, but obviously must do something better. Other conclusions have been made, but none are as significant as the ones I’ve bolded in the above quote.

I’ve decided to do some of my own research on neuropsin, to see what we know of it… where it’s located, what sorta promoters it has, etc. So I fired up NCBI’s GenBank and put in ‘neuropsin‘. Sadly, no current genomic information on the gene is up there yet. Some interesting nucleotide and protein sequences are there, as well as a cool 3d model of the protein.

Most importantly, neuropsin has been identified to function as “A Serine Protease Expressed In The Limbic System Of Mouse Brain.” A protease is an enzyme that basically breaks up things, and since serine prefixes it… neruposin functions as a breakdown component of serine, a hydrophilic amino acid that is a constituent of most proteins. Currently three human diseases are attributed to the malfunction of this enzyme, which I wonder what implications that has as far as symptoms? Reduced cognitive functions?

I also wonder why humans have this alternative modified protein in our brains and not chimpanzees, now that I know the function? Does having a second type of neuropsin allow for us to process serine more effectively, ultimately facilitating some of our cognitive differences? I know I already asked that but it is something I don’t fully understand. That’s something the authors advocate to be studied in the future, to identify,

“the biological function of type II neuropsin in humans, as the extra 45 amino acids in this form may cause protein structural and functional changes. They note that in order to understand the genetic basis that underlies the traits that set humans apart from nonhuman primates, recent studies have focused on identifying genes that have been positively selected during human evolution. They conclude, “The present results underscore the potential importance of the creation of novel splicing forms in the central nervous system in the emergence of human cognition.”

Very interesting news, none the less. Definately one of those genes to keep in the back of your head, no pun intended… really. If you like this sorta stuff, please keep in touch with me, and also check out John Hawks who published out an issue of the neuroscience blog carnival, Encephalon. I wish this post coulda made today’s issue, but I just got word of it midday! Maybe next time.

P.S. This article on ‘stalled human evolution‘ maybe also of interest. I haven’t read it yet, but with a headline like that, its bound to have some controversial stuff in it.