The mysterious genome forms the thumb in humans

Of the 3 billion genetic information in the human genome, Yale scientists have recently discovered some information that contributes to evolutionary changes in human limbs, allowing us to stand upright. and use tools.

Research conducted based on a comparative analysis of humans, chimpanzees, brown monkeys and other genomes shows that our human evolution is probably not just due to a number of sequence changes in the proceeding gene. , but also changes in the gene regions once considered a mysterious DNA area ('junk DNA'). The study was published in Science.

These mutations activate the gene, creating the original thumb and big toe in the mouse embryo.

James Nooan, assistant professor of genetics at Yale University School of Medicine and author of the study, said: 'Our research has uncovered a genetic contributor to phenotypic changes. basic between humans and gibbons'.

Researchers have long suspected that changes in gene expression have contributed to human evolution, but it is difficult to understand this until recently due to most sequences of control. The gene has not been identified. In the past few years, scientists have discovered that non-coding regions in the genome contain thousands of control elements that act as genetic switches to turn on and turn off genes.

A rapid evolutionary sequence in the human genome even controls gene activity that forms the thumb, big toe and ankle in mouse embryos. This suggests that this sequence may have contributed to key evolutionary changes in the limbs of people who help us stand up and use tools.

Many of the non-coding sequences of them are quite similar, or in other words, 'preserved' , even through the evolutionary process of vertebrate animals that have distant relations like chickens. with people. Recent genetic function studies have shown that some 'preserved non-coding sequences' control genes that direct human development.

A rapidly evolving gene sequence in the human genome controls gene activity to form the thumb, wrist and ankle in mouse embryos.(Photo: Image courtesy of Yale University)

In collaboration with scientists at Lawrence Berkeley National Laboratory in California, the Singapore Genome Institute and the UK Medical Research Council, Nooan conducted searches for large unencrypted regions in the genome of humans aim to find the sequence of executive genes that have been transformed in human evolution from the ape-like ancestors.

Nooan and his colleagues searched for sequences that carry more base pairs in the human genome than other primates. The fastest evolutionary gene sequence discovered was HACNS1, preserved among vertebrates but accumulated variation in 16 base pairs since humans and chimpanzees split about 6 million years ago. . This is surprising, because the human and chimpanzees' genomes are generally very similar.

By analyzing mouse embryos, Nooan and his collaborators determined how HACNS1 and related sequences in chimpanzees and brown monkeys managed gene expression during development. The human gene sequence controls genes in the formation of limbs in mice, as opposed to sequences in chimpanzees and brown monkeys. The most interesting thing about human evolution is the gene sequence that regulates the expression of the original thumb and the forelimbs as well as the big toe in the posterior limb. The results provide initial evidence that the functional transformation in HACNS1 may have contributed to the adaptation of the ankles, feet, thumbs and wrists in humans. These are the key advantages that underlie the evolutionary success of our species. However, Nooan emphasized that they still do not understand whether HACNS1 causes changes in gene expression for limb development, and whether HACNS1 creates a developmental process just like humans if It is included in the mouse genome or not.

Nooan said: 'The long-term goal is to find many sequences like this, then use the mouse to model their impact on human evolution.'

The National Institutes of Health together with the US Department of Energy coordinate research funding.