Evolutionary effects of mitochondrial segregation and mutation in the development of complex multicellular life with germ line Arunas Radzvilavicius CoMPLEX, University College London, Gower Street, London WC1E 6BT, United Kingdom ∗ Andrew Pomiankowski and Nick Lane (supervisors) GEE, University College London, Gower Street, London WC1E 6BT, United Kingdom (Dated: August 20, 2013) The emergence of multicellularity in eukaryotes transformed the mapping between germ line fitness and adult viability by introducing the effects of mutation accumulation, seg- regation of organelles, division of labour and differentiation. These changes can play an important role in the evolution of extra-nuclear inheritance patterns. The uniparental mode of mitochondrial transmission, traditionally believed to be responsible for the evolution of two sexes, is advantageous, but can hardly spread to fixation in the model populations of unicellular individuals. The amplification of fitness differences, associated with the emergence of multicellularity, facilitates the spread of advantageous mutations affecting extra-nuclear genomes, thus making the fixation of uniparental mode of in- heritance very likely. Early germ line sequestration in multicellular species is believed to protect reproductive cell lineages from the accumulation of deleterious mutations. The existence of species without isolated germ line shows, however, that early seques- tration of germ line is not universally advantageous. In this contribution we analyse the issue in the light of mitochondrial fitness and effects of multicellularity. Despite the constant accumulation of new mutations, late germ line sequestration increases mi- tochondrial variance between reproductive cells, possibly resulting in the improvement of population fitness. Depending on effective mutation rates, either early or late germ line sequestration can be evolutionary advantageous. The proposed model can possibly account for the correlation between mtDNA mutation rates and the evolution of germ line specification modes observed in nature. I. INTRODUCTION 3. The division of labour between information-storing molecules (DNA) and catalysts (proteins); 1. Multicellularity as a major evolutionary transition 4. The symbiosis of prokaryotes yielding eukaryotic The history of life on Earth is the history of gradual cells with mitochondria and/or chloroplasts; adaptations and major evolutionary transitions towards 5. The origin of sexual reproduction; systems of higher complexity. Every transition involves a shift from independently replicating units to the indivis- 6. The cooperation between unicellular organisms to ible and autonomous groups of cooperating entities. The give rise to multicellularity; concept of \individual", as a unit of selection, must there- fore be redefined after every such transition. The follow- 7. The emergence of social groups of multicellular or- ing events in the history of life are generally believed to ganisms. be major evolutionary transitions (Maynard Smith and In this work we are interested in changes induced by Szathm´ary, 1995): the major transition from unicellular organisms to sta- 1. The compartmentalization of the groups of repli- ble complex multicellularity. It is widely believed, that cating molecules; throughout the history of life on Earth multicellularity has evolved independently more than 20 times (Cavalier- 2. The formation of chromosomes from independent Smith, 1991; Kaiser, 2001; Maynard Smith and Szath- replicators; m´ary, 1995). There is significant evidence that the tran- sition occurred only once in metazoans and plants (King, 2004) and multiple times in algae and fungi (Baldauf, 2003; Bonner, 2000; Kaiser, 2001; Kirk, 1998). The tran- ∗[email protected] sition to the primitive form of multicellularity can be di- 2 rectly observed in laboratory conditions in the presence nor immortality, with the exception of some stem cell lin- of predators (Boraas et al., 1998). eages. This is an example of altruistic behaviour, mak- Several essential conditions had to be satisfied for the ing the multicellular individual indivisible. Germ cells, successful emergence of true multicellularity: cooperation on the other hand, are responsible for reproduction only. between lower level entities, division of labour, emergence With the spatial separation of vegetative and reproduc- of new group-fitness level and control or punishment of tive functions, separation in time is no longer necessary. selfish cells (Buss, 1987; Maynard Smith and Szathm´ary, It has been proposed, that the sequestration of germ 1995; Michod and Roze, 2001). Mechanisms required for line protects lineages from origination and vertical trans- the stable multicellularity to evolve must have included mission of defector traits (Buss, 1987, 1983). As the small communication and signalling between cells, adhesion to group of cells is devoted to become the progenitors of all ensure physical stability and regulation of growth, divi- reproductive cells, mutation arising in any of the somatic sion as well as differentiation. It is currently believed that cells is not generally transmitted to the subsequent gen- the essential components of these mechanisms were in- erations. The evolution of germ line sequestration could deed present in unicellular ancestors of multicellular lin- have been an incredibly important transition, allowing eages (Abedin and King, 2010; King et al., 2003; Prochnik the development of complex, highly differentiated and et al., 2010). It is therefore very likely that simple multi- adapted organisms with massive numbers of somatic cell cellularity evolved by adopting existing molecular ma- divisions. Reproductive cell lineages are also believed chinery rather than de novo creation of new complex to experience lower nuclear mutation rates due to lower genotypes. metabolic activity (Drake et al., 1998), and accumulate The emergence of multicellularity created a new type less mutations due to lower number of cell divisions (Mi- of map between the genotype of zygote and adult phe- chod and Roze, 2001). notype, representing the new unit of selection. In the Despite seemingly obvious evolutionary advantages of realm of simple unicellular organisms, cell is an individ- having an isolated lineage of reproductive cells, many ual entity, which means that there is a direct correlation multicellular taxa do not sequester separate germ line between the viability of a cell and the fitness of the in- (Blackstone and Jasker, 2003). Multicellular organisms dividual. Selection acts on a multicellular organism as a that do not acquire an isolated germ line in the earliest whole, therefore viability of distinct cells is not equivalent stages of their development often have a population of to the fitness of the individual. The fitness of a complex pluripotent cells, e.g. cnidarian stem cells or meristem- and highly differentiated organism depends on the perfor- atic cells in plants, which can differentiate into reproduc- mance of its vegetative and reproductive tissues. Every tive cells after later epigenetic modification. It appears tissue is a collection of cells devoted to perform a specific that the possession of germ line is not a necessary re- task. The division of labour in complex multicellular life quirement for the evolution of differentiation in complex forms makes every tissue vitally important. Failure of a multicellular organisms. The question of what selective single tissue leads to a failure of the organism as a whole. forces promote early or late germ line sequestration is still The division of labour and differentiation into distinct largely unsolved (Grosberg and Strathmann, 2007). The tissues therefore have weakened the correlation between answer might not have much to do with the protection germ line genotype and organism phenotype even more. against defectors or deleterious nuclear mutations. In the present work we provide a novel analysis of the costs and benefits of sequestering a germ line from the 2. Benefits of germ line sequestration perspective of mitochondrial fitness. The transmission of mtDNA genes does not follow Mendelian laws of inher- The fitness of a biological entity can be described as itance. Furthermore, multiple copies of mtDNA within a product of two components, the ability to survive and the cell give rise to phenotypic threshold effects (Rossig- the efficiency of reproduction. Vegetative and reproduc- nol et al., 2003) and mutant segregation|phenomena, tive functions of simple unicellular organisms are coupled unique to the genetics of cytoplasmic organelles. Our at the most fundamental level of cell. The same elemen- mathematical model accounts for mutation accumulation tary entity is responsible for both components of uni- and random mtDNA segregation in somatic tissues, as cellular fitness, although the growth and multiplication well as different modes of cytoplasmic inheritance. stages are separated in time. The same is true for most We argue, that early germ line separation can be both primitive multicellular organisms without the division of beneficial and disadvantageous, depending on the con- labour across cells. The transition to true multicellular- ditions such as mtDNA mutation rates and size of mito- ity has separated vegetative and reproductive functions chondrial population. In populations with low mitochon- in spatial dimension by the means of differentiation. So- drial mutation rates, the phenomenon of random segre- matic cells perform vegetative activities, but the informa- gation results