Why are genes less similar better for studying diseases?

Photo: Baboon, Clker-Free-Vector-Images, Pixabay

Baboons show greater resilience to diseases despite their diverse genome, whereas humans, with a singular set of chromosomes, exhibit increased susceptibility – according to a new study published in ,,Cell Genomics”. 

Genetic variations differ in humans as a whole body or within the body in certain tissues. Genetic variation, simplifying, is the number of chromosomal sets expressed in a cell, lining up to tissue further organs. There may be haploid and diploid sets, meaning that in the first case, a single cell contains only one set of homologous chromosomes, i.e. chromosomes that are similar in their shape and size. In the other case, within the cell, a double set of chromosomes is expressed. Different individuals carry similar genetic information, but their variants can differ. These variants are known as alleles, and sometimes the first allele can be completely different from the second. This variation can occur in different regions of the genome. This is why, for example, children from the same parents may have different eye colors, or it can indicate which genes are inherited from the mother, while others may remain hidden unless they are still present.

Now, scientists of the Salk Institute for Biological Studies, USA in a recent study titled,, Genome-wide allele-specific expression in multi-tissue samples from healthy male baboons reveals the transcriptional complexity of mammals” published in ,,Cell Genomics”, prove that these tiniest alleles being two copies of the same gene or a single nucleotides that build up the structure called allele-specific expression are pivotal for the genetic underpinnings of phenotypic variation within species. What’s more than they are crucial to differences in disease susceptibility and responses to environmental factors.

When is it more advantageous to reverse an evolutionary path?

Unexpectedly, they (the allele-specific expression) are to a greater extent profitable for baboons, being more resilient to disease due to their higher gene diversity than for humans. Why? Astonishing paradox in line with the study is that humans may be seen as a product of evolutionary loss in the context of a number of diploid sets of chromosomes, and this is why they become more vulnerable to illnesses. But there is a good message as well. The one is that baboons’ genome, despite being just 94 percent similarity shared with humans (chimpanzee similarity accounts for approximately 98 percent), represents the best example for studying the diseases harming humans and thus their possible cure. How?

Allele-specific expression (ASE) occurs in human genomes, similar to baboons, where roughly 70 percent of the entire protein-coding gene set is involved. These expressions contribute to specific tissues and are influenced by genotypes, which represent the complete genetic material of an organism. The genes we inherit from our ancestors can make us more or less susceptible to disease. For example, as the scientists claim in their study, previous studies have linked ASE to the risk of Crohn disease, cancer development, aging rates, susceptibility to cardiac diseases, and complex phenotypes in other outbred mammals. The fact that baboons have higher levels of coding sequence heterozygosity (higher genetic variation, i.e, two different alleles of the same gene in a selected location/loci) than do humans facilitates the identification of the number of genes that can be assessed for ASE. These factors make baboons an ideal proxy for humans in biomedical studies, write scientists. Why? Because that makes it possible to identify, let’s say, aggressive allele switching observed for instance during tumorigenesis (that leads to cancer). The difference also makes clear the distinction between healthy tissue and abnormal one. It was observed that the switching of aggressive alleles also takes place between healthy, distinct tissue types. The process is enhanced when haplotypes (with less genetic variability) are better expressed and more stable. Why? This is likely because tissue-specific genes experience stronger selection pressure. As a result, they may be more frequently associated with certain loci in genetic material that are more predictive of diseases. Therefore, in this context, unification does not provide a real advantage.