Primatology.net

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

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.

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.

In chimpanzee communities, it pays to be close with your maternal brethren, according to a brand new publication in the latest issue of the Proceedings of the National Academy of Sciences. The large chimpanzee population at Ngogo in Kibale National Park, Uganda, was studied for this research paper both thru behavioral and molecular approaches. I’m assuming the molecular techniques were used to trace pedigrees and lineages.

The specific scope of the research was to assess the kinship relations among male chimpanzees in this population. From the abstract of paper, the research,

“show[s] that male chimpanzees clearly prefer to affiliate and cooperate with their maternal brothers in several behavioral contexts. Despite these results, additional analyses reveal that the impact of kinship is limited; paternal brothers do not selectively affiliate and cooperate, probably because they cannot be reliably recognized, and the majority of highly affiliative and cooperative dyads are actually unrelated or distantly related. These findings add to a growing body of research that indicates that animals cooperate with each other to obtain both direct and indirect fitness benefits and that complex cooperation can occur between kin and nonkin alike.”

What does that mean? We already knew chimpanzee social structure is highly maternal and usually dominant mother chimps raise dominant sons. Well this research adds to this, indicating that sons, or ‘princes’ if you may, establish a network to dominate hierarchy over the population they preside… sorta like a chimpanzee royalty.

I’m a bit uncertain about the statement on how paternal brothers can’t identify one another… On one level, this seems logical. Its very improbable to know “who your daddy is” in a chimpanzee troop. But, a chimpanzee intimately knows his or her mother, because she reared him or her. However chimpanzees have a very high intellectual capacity, and I’m thinking they know at some level who fathered them. I won’t be willing to bet my life savings, but it is very probable.

If you would like to read more about the article, please check it out under this title and link, “The limited impact of kinship on cooperation in wild chimpanzees.” One last note, I’m not surprised this fieldwork & molecular 1,2 combo came from the primatological powerhouse that is Max Planck Institute’s department for Evolutionary Anthropology, are you?

Science just published a whole slew of papers, posters, news articles, and the like on the Rhesus Macaque because the macaque genome, the first monkey genome to be sequenced, has been unveiled today.

I haven’t read all of the content in this special issue, but from what I have skimmed so far it’s all focused on the genome, of course, but also mobile DNA, genetic relations between two macaque populations, the roles of macaques in biomedical research etc. Rhesus macaques have been used as a model organism in biology for quite sometime, and this special edition of Science pays homage to this magnificent Old World monkey.

I’ve rounded up the links, if you’d like to click around and read some more about these monkeys:

• A Barrel of Monkey Genes
• Boom Time for Monkey Research
• Evolutionary and Biomedical Insights from the Rhesus Macaque Genome
• Mobile DNA in Old World Monkeys: A Glimpse Through the Rhesus Macaque Genome
• Poster: The Macaque Genome
• Evolutionary Formation of New Centromeres in Macaque
• Demographic Histories and Patterns of Linkage Disequilibrium in Chinese and Indian Rhesus Macaques

If you can’t check out all the content, I understand. I’ll be upset, but I’ll get over it. At the very minimum, you should check out the interactive poster that aids in

“exploration, as well as embedded video featuring seven scientists discussing the importance of the macaque and its genome sequence in studies of biomedicine and evolution. We have also created an accompanying teaching resource, including a lesson plan aimed at teachers of advanced high school life science students, for exploring what a comparison of the macaque and human genomes can tell us about human biology and evolution. These items are free to all site visitors.”

I’ve included a screenshot of to wet your monkey lovin’ appetite:

Remember when I told you that the genome of the gibbon was to be sequenced, all the way back in July of 2006? At that time, I assumed it will be finished sooner than the 3 years the NHGRI planned out for the project.

Well, I think my estimatation is right on track…. however researchers seem to have fallen into a slight speed trap.

One of the first publications has come out on this ape genome sequencing project, in the journal Genome Research. The paper is titled, “Molecular refinement of gibbon genome rearrangements,” which focuses on a interesting feature of gibbon genetics… that is also the speed trap.

See, gibbons have a genome that is rapidly evolving, more than other apes like us, gorillas, chimpanzees, etc. Parts of the gibbon genome is constantly being rearranged and broken up… which creates a problem for understanding and comparing genes between species. This genetic phenomenon is called karyotyping, and a unique arrangement is called a karyotype. If you are interested, a very prominent karyotype exists only in humans which distinguish us from other great apes.

Here’s a photo from the publishing team which,

“shows a split signal in human metaphase (chromosomes 6 and 9) and the inset image in the upper right corner shows a single signal in the gibbon genome. This is an example of a clone which spans the breakpoint of the rearrangement.”

Anyways, the whole scope of this paper is a report of these karyotypes and to open discussion on why certain karyotypes seem to evolve much more rapidly. The research also shows how Roberto et al. have developed unique ways to develop a framework in order to sequencing the entire gibbon genome, since they can’t really use a human one… due to the difference in karyotypes. Furthermore, the paper provides some insight on how evolution occurs with genomic rearrangement, as well as how chromosomes can become unstable in cancer and other genetic diseases (something I mentioned when I first anounced this project).

Here’s the abstract to the paper,

“The gibbon karyotype is known to be extensively rearranged when compared to the human and to the ancestral primate karyotype. By combining a bioinformatics (paired-end sequence analysis) approach and a molecular cytogenetics approach, we have refined the synteny block arrangement of the white-cheeked gibbon (Nomascus leucogenys, NLE) with respect to the human genome. We provide the first detailed clone framework map of the gibbon genome and refine the location of 86 evolutionary breakpoints to <1 Mb resolution. An additional 12 breakpoints, mapping primarily to centromeric and telomeric regions, were mapped to 5 Mb resolution. Our combined FISH and BES analysis indicates that we have effectively subcloned 49 of these breakpoints within NLE gibbon BAC clones, mapped to a median resolution of 79.7 kb. Interestingly, many of the intervals associated with translocations were gene-rich, including some genes associated with normal skeletal development. Comparisons of NLE breakpoints with those of other gibbon species reveal variability in the position, suggesting that chromosomal rearrangement has been a longstanding property of this particular ape lineage. Our data emphasize the synergistic effect of combining computational genomics and cytogenetics and provide a framework for ultimate sequence and assembly of the gibbon genome. ^“

The Howard Hughes Medical Institute has issued a press release with a more in depth discussion of the experimental design and results. I got the photograph from there as well as the description.

I am interested in keeping up with this research because there’s potential for an outstanding amount of information to come about from all of this. We can begin to understand how karyotyping, along with other types of genetic morphisms have been one of the selective forces in primate evolution, as well as apply this phenomenon to other aspects within science, such as medicine and cancer biology.

The white-cheeked gibbon (Nomascus leucogenys) will be the next species of primate to get its genome sequenced by the National Human Genome Research Institute (NHGRI) in Bethesda, Maryland, accoridng to ScienceNOW Daily News. After decoding the human and chimpanzee sequence, the NHGRI has seen how the benefits of related genomes have helped medicine and other sciences; so the insititution has planned to sequence rhesus macaque, marmoset, orangutan, and gorilla genomes.

The work should help researchers understand primate and human evolution and the role of genes in disease, because related genomes provide a relative point of understanding what is a genetic difference between human and non-human primate and what is a genetic disease. The NHGRI plans to have the genome sequenced by three years…. but I think it will be done sooner.