An example of the non-mendelian inheritance- The mitochondrial inheritance

Vishu Gupta

Gregor J. Mendel was a biologist, mathematician, meteorologist and is popularly known as the father of genetics as he postulated the three laws of inheritance in the 1800s. His seminal paper published in the 1860s named “Experiments in Plant Hybridisation” describes the experiments and the conclusions of the research that led to the three laws of inheritance as the law of segregation, the law of independent assortment and the law of dominance.

Are Mendel’s laws universal?

As mentioned in the book ‘The Growth of Biological Thought: Diversity, Evolution, and Inheritance’ by Ernst W. Mayr that ‘All biological laws have exceptions’, the Mendel's laws of inheritance also follow this. There are certain conditions where Mendel's three laws of inheritance could not be applied. Few classical examples of such cases include the incomplete dominance, codominance, linkage, organellar DNA inheritance for example mitochondrial DNA in humans and plants and the chloroplast DNA in plants and many more.

How is mitochondrial inheritance non-Mendelian ?

Human cells contain the genetic material in the nucleus and in some special organelles called mitochondria. Mitochondrion, the powerhouse of the cell, is a semi-autonomous double-membrane bound organelle that functions by utilizing the gene products from both its own circular genome of 16,569 base pairs and the nuclear genome. The mitochondrial DNA sequence and organization was reported by Anderson et al in 1981. It codes for 37 genes, out of which 13 are protein coding, 22 are tRNAs and 2 rRNAs. There are 2-10 mitochondrial DNA per mitochondrion and there are hundreds of mitochondria in a human cell. Unlike the nuclear genome, the mitochondrial genome is present in hundreds and thousands of copies in each cell of our body, except the red blood cells. Hence, the alleles of the mitochondrial genes are not inherited in pairs, rather they can be inherited in varying percentages.

As opposed to Mendel's law, the mitochondrial genomes are inherited uniparentally, only mothers providing this genome to offsprings in case of humans. During the inheritance of mitochondrial genomes, there is a bottleneck effect which leads to random segregation of the mitochondria in the daughter cells leading to the transmission of varying percentage of mutations from mother to the offspring. The percentage of the mutant allele that is present is known as the heteroplasmy. The phenotypic manifestation of any trait due to variation in mitochondrial DNA depends upon the level of heteroplasmy of the variation.

Why am I interested in studying mitochondrial genetics?

The area of my research involves studying a combination of traits/phenotypes that can arise due to both the Mendelian and non-Mendelian inheritance. Broadly, my research work revolves around understanding the genetics of mitochondrial disorders. Due to the mutations in either the mitochondrial or the nuclear genome, when the powerhouse of the cell becomes weak, it gives rise to a class of heterogeneous disorders called mitochondrial disorders.

Since, the mitochondria are under dual genetic control, therefore, they follow various modes of inheritance applicable to the nuclear as well as the mitochondrial genome. Unlike the mitochondrial disorders due to mutations in the nuclear genome, the phenotypic expression of these disorders caused due to mutations in the mitochondrial genomes is largely dependent upon the level of the heteroplasmy of the variant allele i.e. the percentage of mitochondrial genomes possessing the variant.

Why is it important to study mitochondrial disorders?

As per the United Mitochondrial Disease Foundation (UMDF) 'every 30 minutes a child is born who will develop a mitochondrial disease by age 10' . Owing to the complex genetics and overlapping clinical presentations with many common diseases, these disorders remain largely undiagnosed. As per a survey in the U.S. , a patient on an average sees 8.19 clinicians before arriving at the final diagnosis of such disorders. Therefore, using the next generation sequencing approaches that have revolutionized the understanding of genetics and have helped in reducing the public health burden, we are trying to understand the genetics of mitochondrial disorders in India. We hope that this knowledge base would aid in the development of scalable and affordable genetic tests and could provide faster clinical diagnosis leading to better management or treatment for patients.