Azim Surani

Azim Surani demonstrated that both paternal and maternal genomes are indispensable for normal mammalian development and subsequently discovered genomic imprinting that confers specific modifications and complementary functions to each genome. Furthermore, he has played a pioneering role in elucidating its underlying mechanisms, thereby making contributions to foundational scientific insights across a broad spectrum of life science fields.

Azim Surani demonstrated that in mammals, male and female genomes receive distinct “imprints” during each germ cell development and these genomes play complementary roles in embryogenesis. Genomic imprinting is a fundamental principle in life sciences that introduces a novel concept to Mendelian genetics. Its discovery represents a pioneering and foundational contribution not only to developmental biology and epigenetics but also to a wide range of life science fields including physiology, regenerative medicine, reproductive medicine, and plant science.

In diploid organisms, including humans, the genome is comprised of numerous genes. For each of these genes, there is a pair of alleles, with one allele typically inherited from the father and the other from the mother. In basic Mendelian genetics, the function of a gene is considered equivalent regardless of whether it is on a paternal or maternal allele. Surani was one of the researchers who developed the “pronucleus transplantation technique,” a method involving the removal and exchange of the male and female pronuclei formed in mouse fertilized eggs. Using this technique, he revealed that: 1) normal mouse development requires one set each of paternal and maternal genome, 2) androgenetic embryos (containing two sets of male genomes) exhibited relatively robust development of extraembryonic tissues but suffered from impaired embryonic development, leading to lethality, and 3) conversely, gynogenetic embryos (containing two sets of female genomes) showed relatively good embryonic development but displayed defects in extraembryonic tissue development, also resulting in lethality (1–3). Based on these discoveries and subsequent investigations, Surani proposed the genomic imprinting hypothesis, suggesting that male and female genomes receive specific modifications during their respective germ cell development, which confer complementary functions to each genome (2–5).

This series of achievements was groundbreaking, as it defied the classical Mendelian assumption that the function of a gene is equivalent regardless of its parental origin. Consequently, it stimulated numerous life scientists to enter this field. Subsequent research has demonstrated that mammalian genomes, including those of humans, harbor approximately 200 imprinted genes (approximately 1% of all genes), which are often clustered on chromosomes. It has been shown that their expression is regulated by DNA methylation within regions termed imprinting control regions, and that sex-specific DNA methylation patterns are established in these regions during germ cell development. Surani also made pioneering contributions in these later studies (6–10).

The discovery of genomic imprinting and the subsequent elucidation of its underlying mechanisms significantly contributed to the dawn and rise of epigenetics, the field studying the mechanisms of inheritance of gene function changes without alterations in the DNA sequence. Imprinted genes are involved in a wide range of biological processes, including development, growth, metabolism, and behavior (11, 12), and their dysregulation is associated with various diseases. Furthermore, accurate regulation of genomic imprinting serves as an important indicator for assessing the quality of pluripotent stem cells, their differentiated derivatives, and cultured human embryos. In addition, in angiosperms (flowering plants), genomic imprinting has been shown to be involved in endosperm development, where imprinted genes regulate seed formation through positive and negative control of endosperm development.

Thus, Surani’s discovery of genomic imprinting and elucidation of its molecular mechanisms represent pioneering achievements that underlie extensive disciplines of modern life science, making substantial contributions to the advancement of life sciences.

References
(1) Surani MA & Barton SC (1983) Development of gynogenetic eggs in the mouse: implications for parthenogenetic embryos. Science 222: 1034–1036.
(2) Surani MA, Barton SC, & Norris ML (1984) Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis. Nature 308: 548–550.
(3) Barton SC, Surani MA, & Norris ML (1984) Role of paternal and maternal genomes in mouse development. Nature 311: 374–376.
(4) Surani MA, Barton SC, & Norris ML (1986) Nuclear transplantation in the mouse: heritable differences between parental genomes after activation of the embryonic genome. Cell 45: 127–136.
(5) Surani MA, Barton SC, & Norris ML (1987) Influence of parental chromosomes on spatial specificity in androgenetic ↔ parthenogenetic chimaeras in the mouse. Nature 326: 395–397.
(6) Reik W, Collick A, Norris ML, Barton SC, & Surani MA (1987) Genomic imprinting determines methylation of parental alleles in transgenic mice. Nature 328: 248–251.
(7) Ferguson-Smith AC, Cattanach BM, Barton SC, Beechey CV, & Surani MA (1991) Embryological and molecular investigations of parental imprinting on mouse chromosome 7. Nature 351: 667–670.
(8) Sasaki H et al. (1992) Parental imprinting: potentially active chromatin of the repressed maternal allele of the mouse insulin-like growth factor II (Igf2) gene. Genes & Dev. 6: 1843–1856.
(9) Ferguson-Smith AC, Sasaki H, Cattanach BM, & Surani MA (1993) Parental-origin-specific epigenetic modification of the mouse H19 gene. Nature 362: 751–755.
(10) Kaneko-Ishino T et al. (1995) Peg1/Mest imprinted gene on chromosome 6 identified by cDNA subtraction hybridization. Nat. Genet. 11: 52–59.
(11) Lefebvre L et al. (1998) Abnormal maternal behaviour and growth retardation associated with loss of the imprinted gene Mest. Nat. Genet. 20: 163–169.
(12) Li L et al. (1999) Regulation of maternal behavior and offspring growth by paternally expressed Peg3. Science 284: 330–333.