Mammal Developmental Genetic Program First Decode

The genetic program that controls major long-term development before and after birth of humans and some animals has been deciphered for the first time.

Heidelberg University molecular biologists in Germany use next-generation sequencing technology to precisely measure the brain, heart, liver, kidneys, testicles and ovaries of these animals, including rhesus monkeys, rats and mice, rabbits and pocket rats. To identify gene activity networks that regulate long-term development.

This study has proved that all the institutions in question, in particular, represent a basic and primitive genetic activity network derived from early mammalian evolution 200 million years ago.

In the second large-scale study, the researchers first explored the role of the so-called RNA gene in the bio-development, which has not been fully understood until now, but forms a large gene category. This RNA gene produces ribonucleic acid, unlike “normal” genes that produce proteins.

The study was published on the 26th of last month in the journal Nature.

The researchers identified higher-level patterns in the sequence of long-term developmental genetic programs. The initial stages of development of all mammals studied were similar, but changed over time. The traits of organs that characterize the species are not revealed until late in the developmental stage. © Kaessmann research group
The researchers identified higher-level patterns in the sequence of long-term developmental genetic programs. The initial stages of development of the mammals studied were similar, but changed over time. The traits of organs that characterize the species are not revealed until late in the developmental stage. © Kaessmann research group

Read over 100 billion protein and RNA fragments

Gene expression regulates the development from embryonic cells to adult organisms through the interplay of precisely tuned and complex genes.

Previously, understanding of these essential genetic programs in mammals has been limited to individual protein genes and specific organ or developmental stages. Moreover, most previous studies were performed primarily on mice.

Professor Henrik Kaessmann, group leader of the Mammalian Genome Functional Evolution Research Group at the Heidelberg Center for Molecular Biology (ZMBH), said, “The genetic basis for describing organ size, structure and function differences in different mammals is almost There is nothing known, “he said.

Professor Casman’s team has adopted an innovative methodology that greatly improves throughput to thoroughly investigate development programs. This next generation sequencing technology (NGS) has the ability to simultaneously analyze all gene expression in each genome.

Using NGS, the researchers read more than 100 billion protein and RNA gene expression fragments from organs from several mammals.

Dr. Margarida Cardoso-Moreira and Ioannis Sarropoulos, the first authors of the two papers describing the study, said: “This reading quantifies the gene activity that moves during development, I was able to compare them. ”

A study of genetic activities of mammalian long-term development in three dimensions, mammalian species, organ, and developmental stages. The evolutionary relationships of the species are shown in the form of branches on the left side of the cube, and typical gene expression in different organs develops on the right side of the cube. CREDIT: Kaessmann research group
A study of genetic activities of mammalian long-term development in three dimensions, mammalian species, organ, and developmental stages. The evolutionary relationships of the species are shown in the form of branches on the left side of the cube, and typical gene expression in different organs develops on the right side of the cube. Ⓒ Kaessmann research group

From 200 million years ago, the prospect of mammalian long-term developmental regulation

Bioinformatics analysis of the data was performed using a high performance computer at the Heidelberg Computing Center. The researchers were able to gain new insights into the genetic control of mammalian long-term development through this analysis.

The basic and primitive genetic activity network discovered by the researchers determined similar functional and key developmental processes in all studied mammals, including humans.

This means that this molecular network has already regulated the long-term development of early mammals 200 million years ago.

The researchers also surprisingly found numerous genes with significantly different patterns of activity in various mammalian species. These differences in the process of evolution explain the particular organ features of each species.

For example, in the case of genes that regulate brain development, the researchers were able to identify distinct patterns of expression in humans.

The process by which human embryos are differentiated. In the course of mammalian evolution, genes with different activity patterns appeared and the characteristics of the organs of each species changed. CREDIT: Wikimedia / Zephyris
The process by which human embryos are differentiated. In the course of mammalian evolution, genes with different patterns of activity have appeared and the characteristics of organs of each species have changed. Ⓒ Wikimedia / Zephyris

First-time confirmation of breakthrough biology hypothesis

The researchers also discovered the surprising fact that a number of RNA genes are involved in long-term development. This kind of genes, which were previously difficult to characterize, play an important role in the development of mammals, Professor Casman said.

The ZMBH research team has identified a higher level of patterns in the sequence of genetic programs through this large-scale study. Genetic programs are still alike in the early stages of development of all studied mammals, but their directions have gradually changed over time.

“The trait of an organ that characterizes a species does not originate until after the developmental stage,” Casman said. “We were able to identify the first breakthrough biology hypothesis in the 19th century using modern molecular methods.”

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