The genetic blueprints of pigs and humans share a surprising number of similarities, making the pig a leading model organism in biomedical science. Understanding this genetic overlap is necessary to appreciate the pig’s utility, ranging from modeling human diseases to serving as a potential source for life-saving organ transplants. The comparison focuses on the functional conservation of genes that govern basic biological processes.
Genomic Similarities and Differences
Pigs and humans share a significant portion of their genetic material, with estimates suggesting that pigs possess approximately 89 to 98 percent of the genes found in the human genome. This similarity lies primarily in the functional, protein-coding regions that direct the basic operations of a cell, rather than the exact base-pair sequence across the whole genome. The pig genome is considered three times more similar to the human genome than that of the mouse.
Despite the functional overlap in genes, the organization of the DNA differs substantially between the two species. The human genome has 23 pairs of chromosomes (46 total) and contains about 3.5 billion base pairs. Conversely, the pig genome is slightly smaller at around 3.0 billion base pairs and is organized into 19 pairs of chromosomes (38 total). The difference in chromosome number reflects large-scale structural rearrangements that occurred since the species diverged.
Shared Physiological Pathways
The functional similarity in the genetic code translates directly into shared biological systems, making the pig an excellent proxy for studying human health and disease. Pigs are a preferred large-animal model for metabolic disorders. Like humans, their omnivorous diet and proportional organ sizes allow them to spontaneously develop conditions such as metabolic syndrome. Researchers can induce a state in pigs that closely mimics the human disease, including obesity, hypertriglyceridemia, and insulin resistance.
The pig cardiovascular system also closely resembles that of humans, which is a major factor in their use for research. The pig heart has a similar heart size-to-body weight ratio and a comparable distribution of the coronary blood supply. Pigs also possess minimal pre-existing coronary collateral vessels, much like humans. This makes them suitable models for studying human coronary artery disease and testing new cardiac stents or surgical techniques.
Genetic Modification for Xenotransplantation
Simple genetic similarity is insufficient for successful pig-to-human organ transplantation, or xenotransplantation, because the human immune system immediately recognizes pig tissue as foreign. The first hurdle is hyperacute rejection (HAR), triggered within minutes by the recipient’s natural antibodies attacking specific sugar molecules on the pig organ’s cells. Scientists use CRISPR-Cas9 technology to delete the $\alpha$-1,3-galactosyltransferase ($GGTA1$) gene, which produces the primary $\alpha$-Gal sugar antigen responsible for HAR.
Once hyperacute rejection is prevented, the next challenge involves delayed immune response and coagulation dysfunction. To address this, human genes are inserted into the pig genome to “humanize” the organ. These transgenes include human Complement-Regulatory Proteins ($hCRPs$), such as CD46 and CD55, which protect the pig cells from the recipient’s immune attack. Other modifications involve inserting human coagulation-regulatory proteins, like Thrombomodulin ($hTBM$) and Endothelial Cell Protein C Receptor ($hEPCR$), to prevent blood clots. A further refinement is the addition of genes like human CD47, which suppresses the activity of human macrophages.
Managing the Risks of Interspecies Transfer
A significant safety concern in xenotransplantation is the risk of transmitting infectious agents from the pig to the human recipient. This risk centers on Porcine Endogenous Retroviruses (PERVs), which are ancient viral DNA fragments embedded throughout the pig genome. Although it is unknown if PERVs cause disease in humans, their ability to infect human cells in a laboratory setting makes them an unacceptable hazard for clinical use.
Scientists address this risk by using CRISPR-Cas9 to precisely target and deactivate all PERV genomic sites. This process has successfully created PERV-free pig lines, which are considered a safer source for organs and tissues. Managing delayed immune rejection remains an ongoing challenge, as subtle inflammation and antibody-mediated rejection can still occur weeks after transplantation. The current strategy is a multi-gene editing approach combining the deletion of pig immune triggers with the insertion of human protective genes to ensure long-term organ survival.