Archive for the ‘Genetics’ Category
The Mountain Gorilla comeback
The Mountain Gorilla, Gorilla beringei beringei, is the primate comeback kid.
I previously shared news with you that their population has been making a rebound. Since then, The Times has published a news article on this topic. (Thanks, Paulin!) Before we get into it, I wanted to say that I haven’t noticed any US news sources report on this, which is disheartening. But anyways, I won’t let that get me down. It’s not often good news like this comes around. Suffice to say, I’m pretty ecstatic to tell you that mountain gorilla populations have,
“been boosted by 12 per cent over the last decade in Uganda…
Mountain gorillas, Gorilla beringei beringei, are one of the most threatened animals in the world, with only 720 left in the wild after years of decline in the face of hunting by humans and habitat loss.
In Bwindi, in southwest Uganda, where they live in a national park, genetic analysis of stools revealed that the population had risen by 40 to 340 in ten years.”
The article goes on to write how this has broke down to be an average increase of 1%, which is a steady increase indicating a healthy, thriving, and well-protected population. But that doesn’t mean the conservation effort for these primates is all done and good now. A population of under 1,000 individuals is still critically endangered.
A lot can still be done to improve their comeback into a full blown population rebound. One thing that comes to mind is to control your cell phone purchases. I know it sounds unrelated, but cell phone manufacturing has a tie-in with gorilla habitats. Another factor to keep in mind goes out to you eco-tourists. Don’t visit the gorillas if you are sick. They are capable of getting our infectious agents, and actually are even more susceptible, because they do not have the acquired immune resistance we do.
Keeping track of Primate Conservation
A new public database has been released that overviews the status of endangered and almost extinct animals. I feel like it is a critical and timely resource, especially in regards to primate conservation efforts.
The project is called EDGE, and currently lemurs are at the top of the most critically endangered primates on that list, and sadly almost every species of lemur that I know frequent that list. Most of the animals represented on the list are small mammals, many rodents, for example. The mountain monkey of South America has made the list, and at 97 on the list of the most critically endangered is the orangutan (Pongo pygmaeus).
In other conservation news, I’m happy to report that the World Wildlife Fund has issued a statement on the rebound of mountain gorillas, in east Africa. They are,
“making a slow but steady comeback due to a decade of conservation efforts to counter the impact of war and poaching…
…There are now 340 in Uganda’s Bwindi Impenetrable Forest National Park, which is home to nearly half the world’s mountain gorillas, the global conservation group said.
That is a 12 percent growth over the past decade.”
Pretty awesome news, and I must tip my hat off to Paulin and his team, who run the blog Gorilla Protection. Let me remind you they broke the news of the two silverback males slaughtered recently. Their reports come straight from the field, and provide us with a tangible connection to the conservation effort of gorillas. If you don’t visit regularly, please do. Make sure you check out their video of a 2-day old gorilla as well as all their wonderful photos.
Last thing, Science has published some reports that came out from this year’s meeting of the American Association of Physical Anthropologists. One of the reports, related to gorillas, is a study of,
“the nuclear DNA from the two species of wild gorillas indicates that they diverged slowly into two species, apparently taking the better part of a million years.”
Since we were talking about genome comparisons this week, I thought you maybe interested in keeping track of more primate genome related science. Check out the report, here.
How did Mark Henderson, of The Times, interpret that chimps are more evolved?
…Or rather why did Mark interpret this information that way? I know, I know, rhetorical question, to some extent. I don’t think that we are yet at a stage of comparing genetic sequences to say one organism is more evolved than the other. But Mark Henderson, ‘Science Editor’ of the newspaper
..Comparison of the genomes of the two [humans & chimpanzees] has revealed that many more chimp genes than human ones have been the subject of positive evolutionary selection….
….Chimpanzees have evolved more extensively than humans since the two species split from their common ancestors.
[And this refutes the] anthropocentric view that a grand enhancement in Darwinian selection underlies human origins.”
This conclusion is horribly misleading, and I want to clarify that the number of genes that have been positively selected for, is not the primary mode for evolutionary change. Positive selection sometimes manifests itself in copy number variations, or genes within a genome that have been repeated in order to increase the frequency that transcript will be made. That is what the authors of the original paper compared. But, it is where these changes, duplications for example, are made that ultimately facilitate evolutionary change.
If you are still a bit confused let me try and make a more descriptive explanation. The best analogy that I can come up with right now is that a chimp could have 200 pennies in its hand. That’s $2.00. Some would consider me a human, and I would conversely have 20 dimes in my hand, but that’s also $2.00. The same concept applies with the number of positive selection features within a genome. It’s not how many positive selection artifacts one has, but what one has and where is it in a genome.
In another light, chimps have evolved in a much different time frame and continue to evolve in a much different environment, compared to humans. Different selective pressures may affect more genes being modified in a chimpanzee genome, than one in a human one because we are fundamentally different when looked down to the chromosomal level. So how could we fully compare something like this?
What is so ironic, is that Henderson goes to quote the authors of the paper he is reporting on,
“The study… underlines that evolution is not a matter of progress towards a goal, and that it is incorrect to assume that more intelligent species are “more evolved”.”
So why has he and the editors of The Times published the article with the title that chimps are winning this evolutionary race?
I don’t know. I don’t think anyone knows really. There’s no race! If anyone is ‘winning the evolutionary race’ it is humans, we are unfortunately decimating chimpanzees. But enough ranting. I will hold out to see what the official publication concludes, once its out. All I know is that it will be published in PNAS under the title and link, “More genes underwent positive selection in chimpanzee evolution than in human evolution.”
If you wanna read more about genomic comparisons between humans and other papers, I’ve written a lot about recent papers that discussed this topic. It should be noted that in these recent papers, different conclusions were made from the ones that Henderson is reporting on. So that maybe of interest to you. Here’s a list of links:
- Mapping out recent evolution on the human genome.
- A new study of copy number variation in chimpanzee genome.
- The contribution of Copy Number Variations (CNV) to human genetic variation.
- Identifying the characteristics of the Fastest Evolving Regions of the Human Genome.
Oh yes, how could we have a discussion of genome comparisons of primates without linking up John Hawks? He also writes about positive selection in human-chimpanzee genome comparisons.
Science magazine unveils the Macaque Genome
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:
Genetic study confirms three chimpanzee subspecies
Most people possessing any familiarity with our closest relatives know that there are two species of chimpanzees: Bonobos (Pan paniscus) and
the common Chimpanzee (Pan troglodytes). Some researchers believe that bonobos and common chimps diverged around 0.9 million years ago (Won and Hey, 2002).
Many may not know that taxonomies further divide common chimps into three subspecies, represented by three distinct populations separated by geographic divisions (e.g. distance, rivers). They are the Western, Central, and Eastern, known as Pan troglodytes versus, Pan troglodytes troglodytes, and Pan troglodytes schweinfurthii, respectively (Groves, 2001).
Previous genetic studies, combined with the nearly complete absence of behavioral or morphological differences, have led some to conclude that the populations are not distinct subspecies (Fischer et al., 2004). In contrast, a new study by researchers from four different institutions seems to show that the three common chimpanzee populations are indeed genetically distinct, and that little or no gene flow occurs between the groups (Becquet et al., 2007).
Recently published in PLoS Genetics, Genetic structure of chimpanzee populations reports on the largest genetic study of chimps to date. They analyzed the genetic material from 84 individuals: 6 bonobos and 78 common chimpanzees.
Their conclusions:
- The western, central, and eastern subspecies designations correspond to clusters of individuals with similar allele frequencies;
- There is little evidence for admixture between groups in the wild; and
- Central and eastern chimpanzees are most closely related in time to each other than either of them are to western chimps.
They failed to find any support for a fourth subspecies (Pan troglodytes vellorosus), originally proposed following mtDNA studies of chimpanzees living near the Sanaga river in Cameroon (Gonder et al., 2006).
References:
- Becquet C, Patterson N, Stone A, Przeworski M, Reich D (2007) Genetic structure of chimpanzee populations. doi:10.1371/journal.pgen.0030066.eor
- Fischer A, Wiebe V, Paabo S, Przeworski M (2004) Evidence for a complex demographic history of chimpanzees. Mol Biol Evol. 21:799-808.
- Gonder MK, Disotell TR, Oates JF (2006) New genetic evidence on the evolution of chimpanzee populations and implications for taxonomy. International Journal of Primatology 27:1103-1127.
- Won YJ, Hey J (2002) Divergence population genetics of chimpanzees. Mol Biol Evol. 22, 297-307.
[Map from Wikipedia]
Reassessing the time at which human-chimp lineages diverged
A new statistical calculation called the hidden Markov model has been applied to four regions of the human, chimpanzee and gorilla genomes as reported in the PLoS Genetics journal.
But, before I jump into a discussion of the implications of this paper, let me explain to those unfamiliar with the hidden Markov model that it was,
“developed in the 1960s and originally applied to speech recognition.”
The calculation takes observable sequences, such as DNA from several genomes in this case, and seeks to fish out hidden parameters. It does this by isolating common genetic patterns from outliers throughout the genomes being compared. Of which the amount of difference and similarities can help calibrate a molecular clock. If you are curious about this statistical test, please check out Wikipedia’s entry on hidden Markov models.
In the paper, “Genomic Relationships and Speciation Times of Human, Chimpanzee, and Gorilla Inferred from a Coalescent Hidden Markov Model,” the authors analyze the results from these hidden Markov model calculations and claim their findings shifts the gap between human-chimpanzee divergence from 5-7 million years ago to around about 4 million years ago. Furthermore, they claim they have evidence that,
“it took only 400,000 years for humans to become a separate species from the common chimp-human ancestor.”
The abstract, if you care,
“The genealogical relationship of human, chimpanzee, and gorilla varies along the genome. We develop a hidden Markov model (HMM) that incorporates this variation and relate the model parameters to population genetics quantities such as speciation times and ancestral population sizes. Our HMM is an analytically tractable approximation to the coalescent process with recombination, and in simulations we see no apparent bias in the HMM estimates. We apply the HMM to four autosomal contiguous human–chimp–gorilla–orangutan alignments comprising a total of 1.9 million base pairs. We find a very recent speciation time of human–chimp (4.1 ± 0.4 million years), and fairly large ancestral effective population sizes (65,000 ± 30,000 for the human–chimp ancestor and 45,000 ± 10,000 for the human–chimp–gorilla ancestor). Furthermore, around 50% of the human genome coalesces with chimpanzee after speciation with gorilla. We also consider 250,000 base pairs of X-chromosome alignments and find an effective population size much smaller than 75% of the autosomal effective population sizes. Finally, we find that the rate of transitions between different genealogies correlates well with the region-wide present-day human recombination rate, but does not correlate with the fine-scale recombination rates and recombination hot spots, suggesting that the latter are evolutionarily transient.”
You maybe asking, how did they do this? Molecular clocks, friends, which I briefly mentioned above. Molecular clocks are effectively patterns in mutations in genomes that we expect to stay fairly consistent throughout evolutionary time. Previous molecular clocks, as reported on Time Tree, average for the time of nuclear divergence between human and chimpanzee lineages to be around 5.56 million years ago. The new hidden Markov model recalibrates, narrowing several parameters such as the time at which humans diverged from other ape lineages.
The following figures from the paper best portrary the results. You will see errors above the points plotted, and those are associated with the estimatation calculated via hiden Markov model. On the x-axis targets 1 refers to Chromosome 7, targets 106 to Chromosome 20, targets 121 to Chromosome 2, and 122 to Chromosome 20. The first is a population genetics parameter for time of divergence and the second time of speciation.
Note how a, or human chromosomes, sampled, consistently stays around 4mya.
Note how t1, or human chromosomes, compared, stays around 4mya, too. While the error bars are large, the study is pretty convincing. This study is also interesting.
It shows us that up until 4 million years ago, there was a lot of genetic introgression but a complete cessation of gene flow occurred abruptly. As John Lynch, from Stranger Fruit, points out,
“The age of 4.1 million years would apparently put the split during the time of such taxa as Australopithecus anamensis, A. afarensis and Kenyanthropus platyops. It will be interesting to see how this affects our current understanding of hominid evolution.”
Some news reports about this paper:
A new species of gray-cheeked mangabey announced
Professor of Bioanthropology, Dr. Colin Groves, of the Australian National University’s Department of Anthropology has spent sometime studying a population of gray-cheeked mangabey (Lophocebus albigena). And his time spent studying this population has not been in vain. He actually found a novel trait in the skulls of this population of mangabeys, unique enough to be soon be designated as a new species, the Ugandan gray-cheeked mangabey (Lophocebus ugandae), as reported here.
I don’t have a picture of this new species to share you (to the right is a image of a regular gray-cheeked mangabey
), nor do I have a publication where Groves documented his findings. Curiously, he,
“had not thought it a priority to publish it – [he has] so many other things to be getting on with.”
But he did present his findings at the International Primatological Society Congress in Entebbe last year and said he will now publish his findings because the forest this new species inhabits, the Mabira Forest, is threatened
“and the loss of this population would probably mean the loss of about a quarter of the total population of what now turns out to be an endemic species.”
Which is commendable. But that statement makes me wonder if the Mabira deforestation pressure not been around, would Groves ever publish his findings?
Furthermore to complicate the validity of this news species, Groves spoke candidly of his method that he used to speciate the new Ugandan mangabey. He calls his method ‘multivariate analyses’ which means to me one relies on two or more variable traits…. but all he shares with the news is one skull measurements! He intends to expand his study, using multivariate analysis to clarify whether other recognized subspecies of Lophocebus albigena can be broken to species level (osmani, johnstoni), which I think is a bit shakey.
I would much rather people sample DNA and use genetic analysis to define a species of primates. And in this case it is possible to do so. Genetic analysis is far more quantitative, definitive, and reliable than measuring skulls (which is a highly variable phenotype between sexes, ages, and environmental/health pressures of primates).
Making sense of the scrambled Gibbon genome
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.
Detecting Human Caused Population Collapse in Orang-utans from Genetic Data
I’m gonna be sharing with you another state-of-the-orang-utan-union type article, however this time it is in the form of a scientific paper. The paper was just published in PLoS Biology, an open access academic journal… so you can read the first hand scientific accounts from anywhere. It is titled, “Genetic Signature of Anthropogenic Population Collapse in Orang-utans” and here’s the abstract (I’ve bolded what I think is the most impacting part of this paper),
“Great ape populations are undergoing a dramatic decline, which is predicted to result in their extinction in the wild from entire regions in the near future. Recent findings have particularly focused on African apes, and have implicated multiple factors contributing to this decline, such as deforestation, hunting, and disease. Less well-publicised, but equally dramatic, has been the decline in orang-utans, whose distribution is limited to parts of Sumatra and Borneo. Using the largest-ever genetic sample from wild orang-utan populations, we show strong evidence for a recent demographic collapse in North Eastern Borneo and demonstrate that this signature is independent of the mutation and demographic models used. This is the first demonstration that genetic data can detect and quantify the effect of recent, human-induced deforestation and habitat fragmentation on an endangered species. Because current demographic collapses are usually confounded by ancient events, this suggests a much more dramatic decline than demographic data alone and emphasises the need for major conservation efforts.”
The basic premise of the publication is that defrestation has impacted populations of wild orang-utans in North Eastern Borneo to such determental levels that the gene pool can’t support a viable population even if things turn for the better. That was a bit hard for the authors to prove because the effects of very recent human caused population fragmentation among orang-utans on genetic diversity are typically difficult to demonstrate. How can one attribute human caused population fragmentation as the sole factor? What if other things are going on?
In order to answer that question and factor out any other variables the authors first limited their study to orang-utan populations in the,
“Lower Kinabatangan floodplain in Eastern Sabah, a region that has experienced large-scale commercial timber exploitation and agriculture since the mid-1950s. Faecal and hair samples were collected from wild orang-utans during boat surveys along the Kinabatangan River or during line transects to estimate nest densities. Two hundred different animals were genetically identified using 14 microsatellites.”
So they have a pretty large sample size from a region where there’s been a long standing history of human impacted ecological change. That makes for a pretty strong foundation upon to make conclusions. Next, they basically ran three different but complementary tests in order to detect, quantify, and date the decline in orang-utan populations. Here’s a two part summary of the three tests:
- “The first approach is based on summaries of the allelic frequency spectrum and was used to detect either a population expansion or decline. It relies on the loss or excess of rare alleles expected in bottlenecked or expanding populations, respectively, and uses simulations under different mutation models to detect departures from mutation-drift equilibrium.”
- “The two other approaches used were Bayesian methods using the information from the full allelic distributions and shall be referred to as the Beaumont and the Storz and Beaumont method… The two Bayesian methods were applied to two subsets of the data for computational reasons.”
From these tests the authors concluded the following results. The first test yielded an observation that, “all nine samples exhibit a strong and significant signal for a population bottleneck, through the loss of rare alleles.” That just means orang-utans are losing their diversity. There’s no definitive conclusion on what that will do, and when that will cause the orang-utan population to collapse… but it is pretty indicative that once you lose diversity, the probability of survival amongst your population reduces. The second test confirmed the conclusion from the first test or in their words, “the present-day genetic structure of orang-utans is strongly influenced by a dramatic decrease in population size, with no support for growing or even stable populations.” And the last test quanitified a date upon which the population of orang-utans will collapse due to a lack of genetic diversity… and that will be on or before 210 years from now.
That’s such a low blow. I don’t know which is worse news, that orang-utan habitats will be erased within 15 years if we continue deforestation at the rates they are going on at or that this is all futile and orang-utans are so endangered that there’s no hope for them a couple centuries down the line. Now there’s a possibility that the computer models, algorithms, and statistical analysis the authors of this paper used are just probabilities… but it does seem that either way orangs-utans are screwed.
In the last century or so, we have killed off 95% of orang-utans. That statistic by itself is crazy. They are a unique and vital species of great ape. They are the only other great ape, other than humans, who live outside of Africa, and deserve our best efforts for conservation. The first thing we must do, as I advocated earlier, is to cut our dependance on illegal logging. That is something we can all do personally. Use less fresh paper, recyle and reuse. The next thing that needs to be done is to step up efforts in creating a diverse genetic population of orang-utans in captivity. That’s all we got. I hope zoological insitutions step up to the plate and devise a plan to accomplish this common goal…
Examining the genetic variation between humans and chimpanzees may help develop cures for several diseases
In a paper from the November issue of Genome Research, researchers from the Division of Biostatistics and Bioinformatics at the National Health Research Institutes are closely examining the genetic variation between humans and chimpanzees (I don’t have access to it yet – free online access is available to Genome Research articles 6 months after publication, but the article highlighting the paper is available in the China Post). Chimps don’t suffer from some of the debilitating diseases that humans can endure, so looking at our genetic differences may lead to information that might enable scientists to alter gene expression and therefore the environment in which these diseases thrive. More information on gene expression is hoped to play a role in finding cures for Alzheimer’s disease, AIDS, and hepatitis B and C.





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. “