Our reporter Lu Chengkuan
Excavating the history of global population migration and communication, mapping the genetic structure of the oldest modern people in East Asia, "Pastoral People", and tracing the formation of population patterns in northern and southern China... Over the past decade, researchers have used ancient DNA technology to unearth those ancient DNA Thousands of years of genetic information, from which it is stripped, constantly refreshes the cognition of human history.
On July 21, "Cell" magazine published online a review article on ancient DNA technology by Fu Qiaomei's team from the Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences.
The researchers reviewed the development history and breakthroughs of ancient DNA technology, discussed the current technical bottlenecks and solutions, and looked forward to the future development direction and prospects of ancient DNA technology.
High-throughput sequencing to revolutionize ancient DNA research
At present, in the field of ancient DNA research, high-throughput sequencing technology is widely used.
High-throughput sequencing, also known as "next-generation sequencing", is a technique for rapidly determining large amounts of DNA sequences.
Before high-throughput sequencing became commonplace, the field of ancient DNA research could only rely on polymerase chain reaction (PCR) techniques to sequence a few specific DNA fragments.
"The DNA information obtained by PCR technology is extremely limited, and it is difficult to distinguish between real ancient DNA and contaminated DNA." Fu Qiaomei said.
High-throughput sequencing technology can theoretically sequence the information of all DNA molecules in a sample, and the cost is decreasing year by year.
Even ancient DNA can be sequenced very efficiently by high-throughput sequencing.
"Not only that, through bioinformatics, we can also quickly detect whether there is ancient DNA damage in the sample, so as to achieve the purpose of identifying ancient DNA." Fu Qiaomei emphasized.
At present, although high-throughput sequencing has been able to sequence ancient DNA relatively efficiently, because ancient DNA extracts often contain a large amount of contaminating DNA, most DNA molecules sequenced are useless information, and the truly useful ancient DNA sequences are often only It accounts for less than 1% of the sequencing data.
In this regard, researchers have developed a DNA capture technology. By designing DNA or RNA probes, the target ancient DNA can be "fished" from the massive contaminated DNA like fishing.
This technique is widely used in the study of human ancient genomes.
DNA capture technology not only greatly improves the efficiency of ancient DNA sequencing, but also effectively obtains enough data for analysis from some "tough" samples.
For example, genomic studies of ancient southern populations.
The warm and humid environment and local acidic soil in southern my country are not conducive to the preservation of ancient DNA, and ancient DNA research in this area was once blank.
Using DNA capture technology, Fu Qiaomei's team successfully obtained the genome information of 30 ancient southern populations, revealing the genetic history of the population at the intersection of East Asia and Southeast Asia for more than 10,000 years.
Recently, ancient DNA researchers have pushed the limits even further, breaking away from the shackles of fossils and extracting ancient DNA directly from "soil" (sediment).
This technology has been successfully applied in Denisowa Cave and Baishiya Cave, and successfully obtained the DNA of ancient human beings tens of thousands of years ago.
The future can be expected to focus on the physiology and health of today's human beings
Although the field of ancient DNA has been fruitful, ancient DNA research has always been full of difficulties and challenges.
"Ancient DNA itself is extremely susceptible to contamination, and its experiments are also extremely delicate. In the past, ancient DNA extraction and library construction were almost entirely dependent on manual operations." Fu Qiaomei introduced.
Recently, in a few laboratories around the world, some ancient DNA experimental steps have been successfully integrated into a fully automatic pipetting robot platform, which not only saves manpower and material resources, but also reduces the risk of contamination introduced by manual operations.
"However, the current sample pre-processing steps can only rely on manual labor. How to integrate this time-consuming and labor-intensive work into the automated system is the next difficulty that ancient DNA experimental technology needs to overcome." Fu Qiaomei said.
In addition, the application of ancient DNA technology goes far beyond the ancient human genome.
Tracing ancient epidemics and symbiotic microbial evolution through ancient microbial information, using ancient epigenetic information to explore the interaction of ancient animals and the environment, and using ancient proteins to explore human evolution on a larger time scale are all important branches of paleomolecule.
In Fu Qiaomei's view, how to obtain this information more effectively and combine the information in multiple dimensions will be one of the difficulties in future research.
Ancient DNA is genetic information with a timescale, and it has written the evolution and adaptation of human beings over tens of thousands of years from a unique perspective.
The traces of these years not only record the genetic history of human beings, but also continue to affect the physiology and health of today's population.
Fu Qiaomei said that some important functional gene haplotypes of modern humans came from ancient humans, and these genes involved innate immunity, lipid metabolism, high-altitude practicality, skin color, etc.
In addition, the genotypes of hair and tooth phenotypes in East Asian populations also increased in frequency after the Last Glacial Maximum, which the researchers speculate is related to environmental adaptation.
"However, the functions of many special genotypes found in ancient DNA studies have not yet been determined. In the future, these findings can be verified by constructing animal models and combining gene editing technology." Fu Qiaomei said, combining ancient DNA technology with modern Cutting-edge molecular biology techniques will enable a clearer understanding of the impact of human evolutionary history on our current human health.