Comparative genomics reveals surprising connections between species that appear vastly different, such as humans and pigs. While their external appearance suggests a wide biological gulf, their genetic blueprints tell a story of deep, shared heritage. This similarity highlights the universal nature of basic biological processes across the mammalian kingdom. Understanding this shared genetic landscape has profound implications for medicine and human health.
Quantifying the Shared Genome
The genetic resemblance between humans and pigs is remarkably high, particularly within the parts of the genome that code for proteins. Scientists estimate that humans and pigs share approximately 90% to 98% of their DNA, depending on the comparison method used. The higher end of this range refers to the sequence similarity within the roughly 20,000 genes responsible for building proteins and performing cellular tasks. This significant overlap exists because both species are mammals and require the same basic set of instructions for survival. Shared genes govern essential “housekeeping” functions, such as metabolism, DNA repair, and cell division, ensuring the core machinery of a pig cell operates almost identically to a human cell.
When comparing the entire genome, including non-coding and regulatory regions, the percentage of shared DNA tends to be closer to 90%. These differences in the non-coding DNA act as regulatory switches, controlling when and where genes turn on or off. These variations ultimately account for the physical and physiological distinctions between the two species.
The Evolutionary Basis for Mammalian Similarity
The high degree of genetic similarity is a direct consequence of a shared evolutionary past. Humans and pigs both belong to the class Mammalia, tracing their lineage back to a common ancestor. Current estimates place the last shared ancestor of the human and pig lines at approximately 80 to 97.5 million years ago.
This ancient divergence means that both species inherited the same foundational genetic toolkit. Over millions of years, natural selection has acted to conserve the genes responsible for the most basic biological functions because significant alteration to these core genes would likely be fatal. This conservation explains why the proteins involved in respiration, digestion, and circulation are nearly identical between a pig and a human.
The differences that accumulate over time are primarily in the non-coding DNA or in genes that determine species-specific traits, such as morphology or lifespan. Despite the vast time since their evolutionary split, the rate of genetic change in the essential protein-coding regions has been slow.
Practical Applications in Biomedical Science
The close genetic and physiological compatibility between humans and pigs has positioned the pig as a valuable animal model in biomedical research. Pig organs are comparable to human organs in size, anatomy, and physiological metabolism, making them ideal for studying human diseases and developing new treatments. This similarity is most evident in xenotransplantation, which involves transplanting living cells, tissues, or organs from one species to another.
The most prominent application is the use of pig hearts and kidneys as potential replacements for failing human organs. Scientists use sophisticated genetic engineering techniques, such as CRISPR/Cas9, to modify the pig genome and overcome immune rejection. These modifications typically involve a multi-gene approach, often resulting in donor pigs with up to ten or more genetic edits.
One important step is the inactivation of the pig gene GGTA1, which produces the sugar molecule galactose-alpha-1,3-galactose (alpha-gal). This molecule is present on pig cell surfaces but is absent in humans, triggering an immediate immune response known as hyperacute rejection. Removing this gene makes the pig organ less immunogenic to the human recipient.
Further modifications include adding human genes to the pig genome that act as immunoregulators. For example, human genes for complement-regulatory proteins like CD46 and CD55 are inserted to trick the human immune system into recognizing the pig organ as “self.” Additionally, genes that prevent blood clotting, such as human thrombomodulin, are added to reduce the risk of organ failure.
Key Genetic Differences Between Humans and Pigs
While the vast majority of functional genes are shared, the small percentage of genetic difference is responsible for the traits that distinguish a pig from a human. These divergent genetic sequences encode instructions for species-specific characteristics, including variations in physiology, lifespan, and the immune system. The study of these differences is important for overcoming barriers in cross-species organ transplantation.
Immune System Discrepancies
The presence of the alpha-gal antigen in pigs, which is absent in humans, is a significant genetic discrepancy in xenotransplantation. This difference necessitates the inactivation of the responsible GGTA1 gene to prevent immediate organ rejection. Another difference lies in the growth rate and size of organs, requiring the removal of the pig growth hormone receptor gene to prevent the transplanted organ from growing too large in the human body.
Viral Risk
Another genetic hurdle is the presence of Porcine Endogenous Retroviruses (PERVs) integrated into the pig genome. While these retroviruses do not typically cause disease in pigs, there is a theoretical risk of cross-species transmission to the human recipient.