Larger cells have relatively smaller nuclei across the Tree of Life

A new study pub­lished in Evol­u­tion Let­ters finally puts paid to a long-held belief that the ratio between nuc­le­us size and cell size is approx­im­ately constant.

Although recently it has been recog­nised that nuc­le­us size and cell size are not inex­or­ably bound, the idea of a con­stant nuc­le­us to cell size (NS:CS) ratio – the karyoplas­mic ratio – remains per­vas­ive in bio­logy. Not least in can­cer bio­logy where the karyoplas­mic ratio is used in both dia­gnos­is and pro­gnos­is for cer­tain tumour types. 

How­ever, in their new study, Dr Mar­tino Malerba and Prof Dustin Mar­shall found that big­ger cells have rel­at­ively smal­ler nuc­lei; as cells get big­ger, the karyoplas­mic ratio actu­ally gets smaller.

Trans­mis­sion elec­tron micro­scopy image of a cell, show­ing the nuc­le­us. Image: Malerba & Marshall.

It all star­ted when Mar­tino and Dustin noticed that their evolved lines of dif­fer­ent size algae didn’t show a con­stant karyoplas­mic ratio. This piqued their curi­os­ity; were these cells unusu­al or had this been observed in oth­er cells? They star­ted com­pil­ing data on cell size and nuc­le­us size in a range of spe­cies and star­ted review­ing pub­lic­a­tions for state­ments about the karyoplas­mic ratio. To their sur­prise, they found many pub­lic­a­tions refer­ring to a con­stant ratio between nuc­le­us size and cell size, but the data didn’t sup­port that. It was enough to com­pel Mar­tino and Dustin to form­ally assess the karyoplas­mic ratio across a wide range of cell types and species.

They con­tin­ued amass­ing data on cell size and nuc­le­us size across as many spe­cies as they could find. They col­lec­ted meas­ure­ments from 879 spe­cies, ran­ging from microbes to mam­mals. Then they looked for data with­in a spe­cies and assembled 7929 obser­va­tions of both nuc­le­us size and cell size in a diverse range of spe­cies includ­ing yeast, plants and meta­zo­ans. Finally, they returned to the arti­fi­cially size-selec­ted algae (small and large) and tracked nuc­le­us size and cell size across 500 gen­er­a­tions of evolution.

What they found was that while, yes, big­ger cells had big­ger nuc­lei, in rel­at­ive terms big­ger cells had smal­ler nuc­lei. At all three scales of bio­lo­gic­al organ­isa­tion that they looked at (among-spe­cies, with­in-spe­cies, and among evolved lin­eages of the same spe­cies) they saw a sys­tem­at­ic decrease in the karyoplas­mic ratio with increas­ing cell size.

From microbes to mam­mals, lar­ger cells have rel­at­ively smal­ler nuc­lei. Fig­ure by Malerba & Marshall.

Why do lar­ger cells have rel­at­ively smal­ler nuc­lei? The authors sur­mise it might tie into the fact that lar­ger cells also have rel­at­ively lower meta­bol­isms. So, is it because lar­ger cells, with their lower rel­at­ive meta­bol­ic rates are able to meet all of their func­tion­al needs with rel­at­ively smal­ler nuc­lei? Or, con­versely, is it because lar­ger cells, with rel­at­ively smal­ler nuc­lei are only cap­able of sus­tain­ing rel­at­ively lower meta­bol­ic rates? We don’t know.

What we do know is that the decreas­ing karyoplas­mic ratio with increas­ing cell size is remark­ably con­sist­ent across a wide vari­ety of life forms. Mar­tino and Dustin hope that a uni­ver­sal driver for this rela­tion­ship will be identified.

Dr Mar­tino E. Malerba is a postdoc­tor­al Fel­low now work­ing at Deakin Uni­ver­sity (Mel­bourne, AUS) for the Centre for Integ­rat­ive Eco­logy. Prof. Dustin J. Mar­shall is the dir­ect­or of the Centre for Geo­met­ric Bio­logy at Mon­ash Uni­ver­sity (Mel­bourne, AUS). The ori­gin­al art­icle is freely avail­able to read and down­load from Evol­u­tion Let­ter. For more inform­a­tion on Malerba and Mar­shall’s research, and on oth­er stud­ies using size-selec­ted phyto­plank­ton cells, vis­it the Centre for Geo­met­ric Bio­logy web­site (https://cgb.org.au/).