How did we "transform" from monkeys to humans?

Produced by: Science Popularization China

Author: Ran Hao (Biodiversity Genomics Group, Kunming Institute of Zoology, Chinese Academy of Sciences) Zhou Long (Center for Life Evolution, Zhejiang University)

Producer: China Science Expo

In the field of biology, humans belong to a group of mammals called primates. Apes, monkeys... Among primates, humans have many "relatives". We share a common ancestor with them, so who is this common ancestor? How did we become humans step by step? The origin of these primates has always been a concern for people. Recently, with the announcement of the interim results of the primate genome project, we have taken a big step forward in answering this question.

From ancestors to flourishing branches

To answer the question "How did we become human step by step?", we need to understand the intricate evolutionary relationship between us humans and our primate "relatives". The Primate Genome Project has opened the "black box" of primate evolution for us.

Zhang Guojie's team from Zhejiang University and Wu Dongdong's team from the Kunming Institute of Zoology, Chinese Academy of Sciences, in collaboration with scholars from home and abroad, used whole genome data from 50 species of primates to conduct ancestral analysis (that is, to infer the origins of various primate groups).

This work requires samples to have a high coverage of biological groups in order to obtain more accurate results. The samples in this study cover 38 genera from 14 families, including 27 new high-quality genome data, and also include populations that were less involved in previous studies.

Therefore, this study has significantly improved the reliability of the results and species coverage compared to previous studies.

After selecting the primate samples, the research team used the genomes of flying monkeys and tree shrews, two species that are closely related to primates but are not primates, as outgroups to reconstruct the evolutionary relationships of primates and obtain the time when the major groups evolved in different directions in history.

What is the result? This starts with the huge "family" of primates.

There are more than 500 living species of primates, and taxonomists classify them into 79 genera in 16 families of the order Primates.

Primate evolutionary tree

(Image source: Primate images were drawn by Stephen D. Nash, and provided by Zhang Guojie's research group and Wu Dongdong's research group)

Among them, the prosimians (suborder Strepsirrhini) are relatively primitive groups, which are distributed in Africa, South Asia and East Asia. Lemurs, lorises and bush monkeys belong to this group. The main body of modern primates, the simple noses (suborder Haplorrhini), include two major groups, the narrow noses (Catarrhini) and the broad noses (Platyrrhini), the latter of which are also two different evolutionary branches.

Catarrhines are mainly distributed in Eurasia and Africa. One of the more intuitive morphological features is that the distance between the two nostrils is very short. We humans belong to Catarrhines (you can touch your nose to feel this feature). Monkeys in Catarrhines are habitually called Old World Monkeys (according to traditional sayings, Eurasia and Africa belong to the "Old World" and the Americas belong to the "New World"), including baboons, macaques, leaf monkeys, etc.

Another branch of the Catarrhines, the apes, are the sister group of the Old World monkeys and are also distributed in the "Old World". The gibbons in the poem "The monkeys on both sides of the river cry incessantly" belong to the small apes, while chimpanzees, orangutans, gorillas and humans belong to the great apes. In some occasions where we deliberately emphasize our origins, we sometimes call ourselves "naked apes". In the process of evolving from the great apes, humans lost their dense body hair and acquired a more thorough upright walking posture, a more developed brain structure and a more complex social structure.

There are no apes in the Americas. The primates there are platyrrhines, also known as New World monkeys, which include marmosets, capuchins, night monkeys, saki monkeys and spider monkeys. As the name suggests, their nostrils are widely spaced. In addition, the tails of New World monkeys are very flexible and can assist in climbing.

This study concluded that the most recent common ancestor of all primates may have appeared between 68.29 million and 64.95 million years ago. This period is very close to the mass extinction event at the end of the Cretaceous period 65.5 million years ago that caused the extinction of non-avian dinosaurs, and is roughly at the time boundary of the Cretaceous period. This means that the evolution of primates may have been affected by the mass extinction event. As for how it was affected, that is a question that future research needs to answer.

Rapidly evolving brain

The changes in the brain from apes to humans are crucial.

Humans may have the smartest brains in the animal kingdom, with larger brain capacity and more complex cerebral cortex structures. Like other parts of the body, the human brain evolved from primate ancestors.

During the long evolutionary process, the brain capacity of primates gradually increased, the proportion of the brain to the body also gradually increased, and the degree of cortical folding became increasingly complex. In the evolution of primates, there were four key nodes for the significant increase in relative brain capacity, which occurred in the ancestors of the anthropoids, the ancestors of the cathartica, the ancestors of the great apes, and humans.

This trend became particularly prominent after the emergence of great apes such as gorillas, and culminated in humans, who not only have the largest brains of any primate, but also the most complexly folded cerebral cortex.

The evolution of brain capacity in primates and the changes in the genome during this process

(Image source: Brain images from Michigan State University, provided by Zhang Guojie's research group and Wu Dongdong's research group)

The study found that during the evolution of primates, many genes related to brain development were positively selected at key evolutionary nodes, that is, these genes were strengthened by natural selection. Therefore, the researchers speculated that these genes played an important role in the increase of primate brain capacity.

These genes also include some key genes related to brain development that have been discovered in previous experimental studies. Mutations in these genes can cause impaired brain function in mice. For example, microcephaly is a serious neurological defect in humans, and the brain volume of patients is reduced due to the blockage of the ability of nerve cells to proliferate. Genes related to microcephaly have been strongly positively selected in multiple branches and are likely to have played a role in the increase in brain volume in primates.

In addition, the researchers also found that some non-coding regions have undergone accelerated evolution at key points in the evolution of primates. Non-coding regions are DNA regions that do not express proteins, but this region will affect gene expression, such as ultimately increasing or decreasing the amount of corresponding protein synthesis. Many of these regions fall into the regulatory regions of genes related to brain development. These results show that primates have continuously optimized the structure of their brains by regulating the expression of brain-related genes during the long process of evolution.

The above findings show that **primates eventually evolved into a more developed brain form during the evolutionary process, and many genes and their regulatory regions were involved in it, **which enriches our understanding of the molecular mechanism of primate brain evolution.

Searching for Man's Lost Tail

In the process of evolution, humans lost the tail behind them.

Regardless of length, almost all vertebrates have tails. The tail that grows on the buttocks is also called the post-anal tail. For some agile primate species, tails of varying lengths can help them stabilize their bodies, turn and control speed. The tails of platyrrhine monkeys can also serve as a grip to assist in climbing. However, it is worth noting that the ancestors of apes lost their tails, which has become an important feature of apes. How did apes lose their tails?

Interestingly, the tails of apes disappeared completely, and there is no fossil record of ape ancestors gradually losing their tails. The early ape fossils, Proconsul, which lived about 20 million years ago, already had no tails. The loss of tails gave apes the advantage of walking upright, but also lost the ability to use their tails to maintain balance when climbing, which may have promoted some apes to move from the tree canopy to the ground.

Previously, biologists have made some discussions on this issue, speculating on the reasons why apes lost their tails from the perspective of adaptation. At the molecular biology level, relevant research is still very limited, and it is speculated that this phenomenon may be related to mutations in some specific gene regulatory sequences.

In this study, by detecting the changes in the genomes of hominid species relative to other primates, the researchers found that a large number of mutations have accumulated in the non-coding regulatory regions of multiple genes, such as the regulatory region of gene KIAA1217.

Mutations in the KIAA1217 gene in humans may cause spinal and coccygeal malformations and affect the normal development of the spine; in mice, mutations in this gene can lead to a reduction in the number of coccygeal vertebrae. Gene regulatory regions are special regions on DNA that can regulate the function of genes, or in other words, some special DNA sequences. This gene regulatory region is in the enhancer region of the KIAA1217 gene and is in the same topological association domain (TAD) as the gene. This suggests that this gene regulatory region has a strong interaction with the gene and may regulate the expression of the KIAA1217 gene.

The DNA sequence of this gene regulatory region in apes is very different from that in other primates. The researchers speculate that it is likely that mutations in these regions have led to an imbalance in the expression of the KIAA1217 gene, causing apes to lose their tails. Although this hypothesis still needs further research and verification, this discovery has provided new clues for us to better understand the evolutionary history of apes.

Rapid evolution of the regulatory region of the KIAA1217 gene in apes may have led to the loss of their tails

(Image source: provided by Zhang Guojie's research group and Wu Dongdong's research group)

Bones, body shape, digestive system...

During the evolution, the common ancestor of primates continued to evolve in skeleton, body shape and digestive system while adapting to various environments and food. In addition to the rapid evolution of the brain, these aspects of evolution also have an important impact on the adaptability and survival ability of primates. This study also found many important genes related to these changes.

The skeletal system plays an extremely prominent role in the evolution of primates, and genes related to bone development play a particularly important role in the adaptive evolution of arboreal lifestyles. In primate ancestors, four genes related to bone development (PIEZ01, EGFR, BMPER and NOTCH2) were strongly positively selected, and their specific functions need to be further clarified. Researchers also found four positively selected genes (LONP1, BRCA2, NEK1 and SLC25A24) in gibbons. The variation of these genes affects the length of bones, thereby lengthening the forearm, and plays an important role in gibbons' activities and foraging in trees.

Primates vary greatly in size, from mouse lemurs weighing only a few dozen grams to gorillas weighing more than 200 kilograms. Researchers have found several important genes in the genes of the ancestors of great apes that may have influenced the evolution of gorilla body size. One of them is the DUOX2 gene, which is involved in the synthesis of thyroid hormones that are important for physical development. Mutations in the DUOX2 gene can cause mice to become smaller. In addition, there are some genes involved in shaping the regulatory pathways of bone development and body size.

Different primates have different eating habits and corresponding digestive systems. Some primates (such as leaf-eating colobus monkeys) like to eat leaves and have evolved a unique foregut system to adapt to this diet. The study found some key digestive genes that were positively selected in the ancestors of colobus monkeys, accumulating special amino acid variations to adapt to this special diet.

For example, the ACADM gene encodes an Acyl-CoA dehydrogenase that plays a key role in metabolizing ingested fatty acids, and the changes in this gene in colobus monkeys improve their ability to digest fatty acids. For another example, the accumulated NOX1 gene variation can further help colobus monkeys regulate the microorganisms in their bodies, allowing them to better digest leaves. Their intestines can also produce short-chain volatile fatty acids through microbial fermentation, thereby providing more energy.

Association between primate genome evolutionary features and phenotypic traits

(Image source: provided by Zhang Guojie's research group and Wu Dongdong's research group)

Conclusion

The Primate Genome Project not only explored the evolutionary process and speciation of primates including apes (such as the first report of hybrid speciation among primates), but also explored chromosome evolution, rapidly evolving DNA sequences, incomplete lineage divergence of genes, etc. Its achievements go far beyond these. You have to know that this is a huge and in-depth study.

In the journey of searching for the origin of life, biologists never stop because of fear of difficulties. Who are we? In order to answer this question, humans "solve puzzles" in groups of letters and explore the mysteries of evolution. We firmly believe that one day, humans will write a complete story of life.

Note:

Introduction to the Primate Genome Project

There are more than 500 primate species in the world, belonging to 16 families and 9 genera. Non-human primates are of great significance for understanding the origin, evolution, physiological traits, diseases and other aspects of human beings due to their close relationship with humans. Chinese scientists have launched the Primate Genome Project in collaboration with multiple research centers at home and abroad, aiming to study the origin and differentiation process of primate species including humans, as well as the evolution and genetic basis of primate social organization and various physiological characteristics through multidisciplinary cross-technical means and teamwork. In addition, the project will also study the genetic variation map of primates and its impact on the variation pattern of human pathogenic genes.

Primate Genome Project Research Consortium

Professor Zhang Guojie's team from the Center for Life Evolution Research, Zhejiang University

Researcher Wu Dongdong's team from Kunming Institute of Zoology, Chinese Academy of Sciences

Professor Qi Xiaoguang's team from the School of Life Sciences, Northwestern University

Researcher Yu Li’s team from the School of Life Sciences, Yunnan University

Professor Tomàs Marquès-Bonet's team from the Joint Institute of Evolutionary Biology, Pompeu Fabra University, Spain

Illumina Artificial Intelligence Lab

Professor Jeffrey Rogers' team from the Human Genome Sequencing Center at Baylor College of Medicine

Mikkel H. Schierup team from Aarhus University, Denmark

Professor Christian Roos' team from the Leibniz Institute for Primate Research in Germany

Interim research results (11 research papers)

Science Research Issue (8 papers)

Fiziev PP, Mcrae J, Ulirsch JC, ..., Farh K KH. 2023. Rare penetrant mutations confer severe risk of common diseases. Science 380. Doi: 10.1126/science.abo1131.

Gao H, Hamp T, Ede J, ..., Farh K KH. 2023. The landscape of tolerated genetic variation in humans and primates. Science 380. Doi: 10.1126/science.abn8197.

Kuderna LFK, Gao H, Janiak MC, ..., Bonet TM. 2023. A global catalog of whole-genome diversity from 233 primate species. Science 380, 906-913. Doi: 10.1126/science.abn7829.

Qi XG, Wu JW, Zhao L, ..., Li BG. 2003. Adaptations to a cold climate promoted social evolution in Asian colobine primates. Science 380.Doi: 10.1126/science.abl8621.

Rivas-gonzález I, Rousselle M, Li F,..., Zhang GJ. Pervasive incomplete lineage sorting illuminates speciation and selection in primates. Science 380.DOI: 10.1126/science.abn4409.

Shao Y, Zhou L, Li F,..., Wu DD. 2023. Phylogenomic analyzes provide insights into primate evolution, Science 380, 913-924.Doi: 10.1126/science.abn6919.

Sørensen EF, Harris RA, Zhang LY, ..., Rogers J. 2023. Genome-wide coancestry reveals details of ancient and recent male-driven reticulation in baboons. Science 380. Doi: 10.1126/science.abn8153.

Wu H, Wang Z, Zhang Y, ..., Yu L. 2023. Hybrid origin of a primate, the gray snub-nosed monkey. Science 380. Doi: 10.1126/science.abl4997.

Science Advances (2 articles)

Bi XP, Zhou L, Zhang JJ, ..., Zhang GJ. 2023. Lineage-specific accelerated sequences underlying primate evolution. Science Advances 9. Doi: 10.1126/sciadv.adc9507.

Zhang BL, Chen W, Wang ZF, ..., Wu DD. 2023. Comparative genomics reveals the hybrid origin of a macaque group. Science Advances 9. Doi: 10.1126/sciadv.add3580.

Nature Ecology & Evolution (1 article)

Zhou Y, Zhan XY, Jin JZ, ..., Zhang GJ. 2023. Eighty million years of rapid evolution of the primate Y chromosome. Nature Ecology & Evolution. Doi: 10.1038/s41559-022-01974-x.

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