What makes monkeys different from humans

These two proteins are active suppressors of the activity of what we call mobile elements, which are genetic elements that exist in all of our genomes. In fact, 50 percent of the DNA in human genomes is made up of these mobile elements molecular parasites of the genome. So what are mobile elements? They are elements that exist in specific locations in the genome and, through unique mechanisms, they can make copies of themselves and jump from one part of the genome to another.

Barbara McClintock discovered these elements through her work on maize. Some of us study a specific form of mobile elements called a LINE-1 retrotransposon. They exist in thousands of copies in the genome, as a DNA that makes a strand of RNA and then makes proteins that binds back onto the RNA, helping the element copy itself. This combination of mRNA and proteins then moves back into the nucleus where the DNA resides and pastes itself into the genome at a new location.

These LINE elements continue to be active in our genome, and they are particularly active in neural progenitor cells. Not only do humans make more of these proteins, but as an apparent consequence, the lower levels of these L1 suppressors in chimpanzees and bonobos means the L1 elements are much more active in chimpanzees and bonobos than in humans.

When searching the DNA libraries genomes that have been sequenced for chimps, bonobos, and humans, there are many more L1 DNA elements in the genomes of chimps and bonobos relative to humans. This greater number of L1 elements in non-human primate genomes leads to an increase in DNA diversity and, thus, in the diversity of their offspring and potentially in their behavior. This led us to speculate that this decrease in genetic diversity that occurs in humans leads to a greater dependence on cultural adaptive changes to survive as a species rather than genetic adaptive changes.

For example, if a virus were to infect a chimp or a bonobo population, in order for that species to survive it would require a member of the species with the genetic mutation that provided protection in some form from the virus. Humans do not wait for the mutation from a member of the species that would provide protection from the virus.

We build hospitals, we design antibodies, we transmit our knowledge through cultural information cultural evolution rather than relying on genetics genetic evolution for the spread and the survival of the species. I n the s, my research group happened to discover the first known genetic difference between humans and chimpanzees. And so I thought, well, they must be just like us. And, indeed, when I first looked at the major causes of death in adult captive chimpanzees, the number one killer was heart disease, heart attacks, and heart failure.

Again, I thought, well, they are just like humans. But then when I started going over the textbook with the veterinarian, I noticed that not all the diseases were the same. So the question arises: are there human-specific diseases? There are a few criteria for human-specific diseases: they are very common in humans but rarely reported in great apes, even in captivity; and they cannot be experimentally reproduced in apes in the days when such studies were allowed. The caveat, of course, is that reliable information is limited to data on a few thousand Great Apes in captivity.

But these apes were cared for in NIH-funded facilities with full veterinary care — probably better medical care than most Americans get — and there were thorough necropsies. As it turned out, I was even wrong about heart disease. It was not until my spouse and collaborator Nissi Varki looked at the pathology that she realized that while heart disease is common in both humans and chimpanzees, it is caused by different pathological processes.

They developed massive scar tissue replacing their heart muscle, which is called interstitial myocardial fibrosis. There is now a special project called The Great Ape Heart Project, which is providing clinical, pathologic, and research strategies to aid in the understanding and treatment of cardiac disease in all of the ape species. There are actually two mysteries to be solved: why do humans not often suffer from the fibrotic heart disease that is so common in our closest evolutionary cousins?

Conversely, why do the Great Apes not often have the kind of heart disease that is common in humans? We put together a list of candidates of human-specific diseases that meet the criteria I mentioned earlier, and myocardial infarction is number one. Malignant malaria is number two. In studies done from the s to the s, people actually did horrible two-way cross-transfusions between chimpanzees and humans infected or not infected with malaria, and there was no evidence of cross-infection.

In fact, the parasites looked the same, but they were actually completely different. More modern work done by Francisco Ayala and others showed that, in fact, P. Pascal Gagneux and I wrote an article that explains what might have happened. There are multiple forms of ape malaria that are mild throughout Africa. At some point, we escaped because of a change in the surface sialic acid molecule.

Another candidate for human-specific diseases is typhoid fever. More horrible studies were done in the s that showed that large doses of Salmonella typhi did not result in severe cases of typhoid fever in chimpanzees. It can only bind to the human cell surface again, because of the sialic acid difference between the species. Another candidate is cholera, which is a major killer in humans. How does evolution work? What do scientists mean when they call evolution a theory?

How does evolution explain complex organisms like humans? How are humans and monkeys related? Did humans evolve in a straight line, one species after another? How do scientists know the age of fossils? How do scientists know what past climates were like? What has been discovered about evolution since Darwin? Can the concept of evolution co-exist with religious faith? How can we reduce the conflict between religion and science? What about the gaps in knowledge about human evolution? How does scientific knowledge about evolution relate to cultural beliefs about our origins?

Chickens, chimpanzees, and you - what do they have in common? Grandparents are unique to humans How strong are we? Humans are handy! Humans: the running ape Our big hungry brain!

Our eyes say it! The early human tool kit The short-haired human! Imaging was performed in the dorsolateral telencephalon of E Embryonic day E 0. All experiments using mice were performed according to the German Animal Welfare Legislation. PR was obtained as a kind gift from F. Gage Marchetto et al. Sandra A and Toba were generated in collaboration with Shinya Yamanaka following a nonviral transfection method Okita et al.

Briefly, blood was collected from a chimpanzee and an orangutan, both housed at the Leipzig Zoo, and leukocytes were isolated by Ficoll gradient centrifugation, which were then used for reprogramming to iPSCs. DNA sequencing revealed no chromosome aberrations, and RNA-seq and immunohistochemistry confirmed pluripotent gene and protein expression signatures. Primate blood samples used to generate iPSCs were obtained by certified veterinarians during annual medical examinations or other necessary medical interventions, meaning that no invasive procedures were performed on primates for the sole purpose of our research project.

Human endothelial cells. Single cell transcriptome analysis confirmed the identity of human and chimpanzee iPSCs and human endothelial cells, and showed no contamination with other cell lines.

B-cell lines were generated from blood obtained from three human A, A, A and three chimpanzee Dorien, Jahaga, Ulla individuals.

Withdrawal and processing of blood samples was performed according to approved protocols, and was performed for chimpanzee during necessary veterinary interventions. Lymphocytes were isolated from blood using a Ficoll gradient centrifugation.

Immortalization was performed by adding Epstein Barr virus EBV supernatant to the lymphocytes and further cultivation of the cells until colonies of immortalized B-lymphocytes were established Tosato and Cohen, Cell lines were regularly tested for mycoplasma using a PCR-based test Minerva Biolabs and found to be negative. Human and chimpanzee cerebral organoids were generated from the above iPSCs and cultured for the indicated times as described previously for human cerebral organoids Lancaster and Knoblich, ; Lancaster et al.

To generate single-cell suspensions, cerebral organoids were either dissociated as a whole or first sliced using a vibratome to dissect cortical regions. Additional mechanical dissociation was performed by triturating the tissue. Counting of cells was performed using a Countess automated cell counter Invitrogen and by staining with Trypan blue.

These steps were performed as described Camp et al. Resulting cDNA was quantified and checked for its size distribution using a capillary gel electrophoresis system Fragment Analyzer, Advanced Analytical, 1— bps High Sensitivity. Up to 96 single-cell libraries were pooled and cleaned up using solid phase reversible immobilization SPRI beads Thermo Scientific. Up to cells were pooled and sequenced in bp paired-end mode on one lane of an Illumina HiSeq platform rapid mode.

Base-calling, adaptor trimming and demultiplexing of reads was performed using a custom pipeline based on freeIbis Renaud et al. Demultiplexed reads were mapped using TopHat v2. Human reads were mapped to the hg38 reference genome release 77 and chimpanzee reads were mapped to panTro4 release RStudio Team, was used to run R Development Core Team, , scripts to perform principal component analysis PCA, FactoMineR package , hierarchical clustering stats package , differential expression analysis SCDE package , and to construct heatmaps, scatter and line plots, dendrograms, bar graphs, pie charts and histograms.

Generally, ggplot2 and gplots packages were used to visualize the data. The Seurat package Macosko et al. In Figure 1E we calculated for each chimpanzee organoid cortex cell the Spearman correlation of its transcriptome all genes with bulk transcriptome data from each of 4 microdissected human cortical zones VZ, iSVZ, oSVZ, CP, mean expression value of each gene across 4 replicates from 13 weeks post conception, data published in [ Fietz et al.

The scaling enables a better comparison between cells, since the maximum and minimum correlation for each cell is color-coded in the same way after scaling. We used this analysis to identify the zone with which each individual cell had a maximum correlation. Each fetal, human organoid, and chimpanzee organoid cortex cell was scored for the NSPC or neuron signature by summing the number of genes from each signature that have an expression greater than log2 FPKM of 5, and normalizing by the number of all genes expressed above log2 FPKM of 5 for each cell.

To construct the chimpanzee cellular network, we computed a pairwise correlation matrix for all chimpanzee cerebral cortex cells and using genes discovered in PCA of fetal neocortex single cell transcriptomes Camp et al. These same genes had been used to infer lineage relationships in the fetal neocortex. We then generated a weighted adjacency network graph using the graph. The fruchterman reingold layout was used to plot the network graph.

The combined species network was constructed in a similar way using the same genes and a correlation threshold of 0. Monocle Trapnell et al. We re-aligned reads from each cell to a human-chimpanzee consensus genome to account for mapping bias originating from the different genome qualities of the human and chimpanzee genome.

The consensus genome was generated as previously described He et al. In brief, the consensus genome was constructed based on the chained and netted pairwise alignment of human hg38 and chimpanzee panTro4 obtained from UCSC.

Discordant sites and indels including 6 bp upstream and downsteam of the indel position were masked replacing the base with N.

STAR v2. For quantification, HTSeq Anders et al. Resulting count files were combined into one master table containing all cells and genes. To identify differentially expressed genes between human and chimpanzee, cells were first annotated as AP, BP or neuron based on the fetal cortex cell type with which each cell maximally correlated.

A more stringent threshold of twice the standard deviation of the z-score was used to define differential expression between human and chimpanzee Z. For the differential gene expression analysis during mitotic phases, we aimed to identify relatively homogeneous clusters of human organoid APs, chimpanzee organoid APs, endothelial cells ECs , or iPSCs in G2M or G1 phases.

We hierarchically clustered cells Pearson correlation using expression of genes that correlated with PC1 from PCA on human fetal cortex progenitor cells Camp et al. For the organoid APs, this assignment was consistent with an independent assignment using the method published by Scialdone et al.

The secondary antibodies, used in combination with DAPI staining, were all donkey-derived and conjugated with Alexa , or Life Technologies. An average of cells per sample were counted. Statistical significance was calculated using the Mann—Whitney U-test. Cell cycle parameters were determined using linear regression based on a model described previously Nowakowski et al.

Live tissue imaging was performed as described previously Mora-Bermudez et al. Potential phototoxicity was stringently controlled as previously described Mora-Bermudez and Ellenberg, Brightness and contrast of images were recorded and adjusted linearly. Spindle orientation analysis was performed as described Mora-Bermudez et al. In short, the degree values given in Figure 4 are deviations from a perfect orthogonality with the local apical surface plane, as seen from a coronal perspective Figure 4A—F.

For Figure 4G , the maximal range of orientations per every mitotic AP was calculated from the formation of a metaphase plate to anaphase onset. To measure the duration of mitotic phases, the start of each different phase was defined as follows, based on morphology, dynamics and condensation of chromosomes as reported by vital DNA staining Figures 5 and 6.

The total duration of mitosis was the sum of these phases. We note that our measurements of mitotic phases are limited by the use of chromosomes as markers. Statistical tests: for two groups of observations, the Mann—Whitney U-test was used. In the interests of transparency, eLife includes the editorial decision letter and accompanying author responses.

A lightly edited version of the letter sent to the authors after peer review is shown, indicating the most substantive concerns; minor comments are not usually included. Thank you for submitting your article "Differences and similarities between human and chimpanzee neural progenitors during cerebral cortex development" for consideration by eLife. Your article has been reviewed by three peer reviewers, and the evaluation has been overseen by a Reviewing Editor and K VijayRaghavan as the Senior Editor.

The following individuals involved in review of your submission have agreed to reveal their identity: Victor Borrell Reviewer 3. The reviewers have discussed the reviews with one another and the Reviewing Editor has drafted this decision to help you prepare a revised submission. To address this technologically very challenging question, the authors use state of the art approaches including brain organoid cultures and single cell RNAseq.

In a very remarkable methodological tour-de-force, the authors develop brain organoids from human, chimpanzee and orangutan iPSCs, and go on to perform high resolution live imaging of individual progenitor cells. The authors find that same classes of neural stem progenitor cells in humans and chimps are nearly identical at the transcriptome level, and also in their behavior in the cell cycle.

A consistent difference identified by the authors is a lengthening of 5 min of metaphase during cell division. The study is timely and addresses a very important question. The reviewers, however, identified a number of technical and conceptual issues that will require the authors' attention. Reviewer 1's main criticism is conceptual. The reviewer argues that an important part of the regulation of cell cycle progression is post-translational.

As the cell cycle differences were detected in the VZ in AP which is not the major proliferative region in the human and in chimpanzee cortex this finding may not necessarily provide sufficient explanation to the difference between the human and chimpanzee brains. Alternatively, it may be advisable to analyze the changes at the level of protein expression in the AP during metaphase.

In case such a study is beyond the scope of the current paper, the manuscript may be modified emphasizing the validity of the organoid system to study the conservation and diversification of cortical development in different species, the technical advances conducted and how they can assist in approaching such a complex and difficult study.

C The developmental time period for human and chimpanzee is different in vivo. How could the authors account for this age difference in vitro in organoids? Should the time in culture be normalized for gestation length? D What is the evidence that the organoid developmental clock parallels the in vivo clock and how reliably does that clock operate from culture to culture? E The error bars in Figure 2B should not be drawn in a manner that obscures the lower SD boundary-error extends in both directions.

F Although the authors build their story based on Figure 2B there is not much difference in the number of Pax6 Tbr2- cells considered as APs at Day between chimpanzee and human. How many cells are counted per sample? The difference in the number of Pax6 Tbr2 cells between chimpanzee and human is not evident in the immunostaining images in Figure 2A.

The author should provide a better view of the image marking some cells with co-localization of Tbr2 and Pax6. Also, they should comment on what kind of cells are Pax6 Tbr2 cells or comment that the cell type cannot be identified due to the unclear lamination of their organoids. Almost all cells from 45d are clustered as mesenchyme cells and all cells from 62d are clustered as hindbrain cells.

Are those Pax6 Tbr2- cells? In Figures 4 — 6 , no markers have been used to assign those cells as AP. Markers such as Pax6 and Tbr2 with reporter plasmids could be used to trace the cells. This kind of experiment would support the data presented in Figure 2B. In Figure 7 , the authors have tried to address this question but they have used developing mouse neocortex to distinguish proliferative and neurogenic APs. The dynamics of prometaphase-metaphase is very different in mouse as compared to human or chimpanzee, therefore, it is difficult to relate that the lengthening of prometaphase-metaphase characterizes proliferating NPSCs in humans.

However, in Figure 5——figure supplement 1 , no significant difference is shown. Moreover, the bar value for prophase and anaphase does not correlate with the values shown in the live images in Figure 5. Please clarify this difference in figures. Furthermore, they found lengthening of the metaphase in human apical progenitors compared to chimp and no difference was observed in other phases during cell mitosis, but they didn't show whether the length of cell cycle for this kind of progenitors is different, which is also important for cell fate determination.

Moreover, the authors didn't include cells in S phase of cell cycle. If the authors used the same set of genes as described in Camp, Badsha et al. Please explain the method and also explain why S phase is not included in this analysis. What is the difference in the list of genes highly expressed in AP cells in humans obtained in Figure 3E and in Figure 8D? According to the data, it would mean that the prometaphase-metaphase duration could be prolonged by expressing any of these genes in chimpanzee organoid.

Silver has reported that prolonged mitosis of progenitors could lead to apoptosis or differentiation , Neuron. Based on this finding one would draw the opposite conclusion. Reviewer 3's criticism is also mainly conceptual. Nat Comm and others? Are human organoids larger more cells than chimpanzee after a similar period in culture? This simple piece of information may help understand if these organoids are indeed helpful to unravel differences between chimp and human cortex development, and if so where to look.

Do human aRGs undergo more rounds of cell division than chimp? Reviewer 3 also asks: Are the differences observed in length of cell cycle phases and those not observed due to human-chimp differences in brain development? Or rather they may be due to the transition between iPSC and organoid? The authors nicely compare metaphase in blood B cells from chimp and human and don't find differences. But then, will they find similar differences between human and chimp when comparing organoids from other tissues i.

Finally, the reviewer argues: The authors state that "each chimpanzee cell represents a cell state on a continuum from NPSCs to neurons based on gene expression signatures". Whereas one agrees on the concept of transcriptomic continuity across cell types in development, how does this concept fit with the canonical criterion of classifying cell types in the cerebral cortex in discrete groups, as is also done in this study?

Although this is clearly not the main focus of the study, this type of classification analysis is quite used throughout the manuscript, and so the authors would do well in discussing this point. What many people may also not know, is how vital this taxonomy or the systematic classification of organisms is to Dr. It was in fact Dr. Louis Leakey in Kenya, which lead to her initial research in Gombe, Tanzania. Leakey was trying to understand early humans, and because his only point of reference was fossilized early human remains and other preserved cultural materials, he could not completely understand what early human behavior may have been like.

When he met Jane, with her passion for and knowledge about animals, he knew she would be the perfect candidate to study chimpanzees — our closest living primate relative — from which he could conclude what behaviors were likely inherent to our most recent common ancestor and earlier humans.

Zinda fishing for termites in Gombe National Park, Tanzania. In her research, Dr. Goodall made a revolutionary discovery when she observed that the chimps in Gombe were making and using tools. It was groundbreaking because it meant redefining everything that scientists thought they knew about what separated humans and chimpanzees!

It has also lead to the revelation that other animals also make and use tools, have emotions, intelligence and sentience.

Want to know more and to support our ongoing research in Gombe, now the longest running wild chimpanzee study in the world? Become a Gombe Science Hero! Find out more and get involved here.

The Jane Goodall Institute is a global community conservation organization that advances the vision and work of Dr. Jane Goodall. By protecting chimpanzees and inspiring people to conserve the natural world we all share, we improve the lives of people, animals and the environment.

Everything is connected—everyone can make a difference. She has been passionate about the environment and conservation since her parents raised her spending summers camping in the U.