Insight into the genome of Saccharomyces carlsbergensis

Eureka, another yeast genome got recently published (May 2014) by scientists at the Carlsberg Laboratory in Denmark: Saccharomyces carlsbergensis, the world’s first pure lager yeast used in production since 1883. I would like to review the published article and point out some interesting results. Below the full reference of the paper I am talking about.

Walther A, Hesselbart A, Wendland J (2014) Genome Sequence of Saccharomyces carlsbergensis, the World’s First Pure Culture Lager Yeast, G3, 4:783-793; doi:10.1534/g3.113.010090, http://g3journal.org/content/4/5/783.full

The scientists sequenced the genome using next generation sequencing techniques and compared the genome with Saccharomyces cerevisiae (top-fermenting yeast) and Saccharomyces eubayanus (likely to be a parent of the lager yeasts). Lager yeasts are hybrids and resulted from an interbreeding event between a top fermenting S. cerevisiae yeasts parent as well as a non-cerevisiae parent (likely to be S. eubayanus). This means, the genome of lager yeasts consist of parts of the S. cerevisiae genome as well as parts of a non-cerevisiae parental genome.

Beside S. carlsbergensis, the authors re-sequenced another lager yeast (Weihenstephan WS34/70) for comparative reasons. Lager yeasts can be grouped into group I (Saaz-type lager yeasts) and group II (Frohberg-type lager yeasts). Members of the two groups reflect geographic associations with breweries like group I (Czech and Carlsberg) and group II (Weihenstephan and Heineken). The sequenced S. carlsbergensis strain (CBS1513) belongs to group I whereas WS34/70 belongs to group II. Comparing the two genomes therefore might give some insight into genetical differences between the two lager yeast groups.

Loss of parental S. cerevisiae DNA in S. carlsbergensis

The authors found substantial genome size differences between the two lager yeasts (about 3.5 Mb). A previous investigation showed, the Weihenstephan lager yeast contains two complete parental genomes (S. cerevisiae and S. eubayanus) with some losses at chromosome ends [Nakao et al, 2009]. To address how much of the S. carlsbergensis genome is from S. cerevisiae and S. eubayanus, the authors mapped the obtained S. carlsbergensis genome to the two parent yeast genomes. The comparison revealed, the genome of S. carlsbergensis does not contain information of the S. cerevisiae chromosomes VI, XI and XII (Fig 1, left), harbours some translocated S. eubayanus chromosomes (II, IV and VIII and XV) (Fig 1, right) as well as loss of heterozygosity in some S. cerevisiae chromosomes (Fig 1, right, chromosomes IV, XIII, XV and XVI). This lack of chromosomal information of S. cerevisiae chromosomes VI, XI and XII as well as some loss of heterozygosity is sufficient to explain the smaller genome size of S. carlsbergensis in comparison with the Weihenstephan lager yeast.

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Fig 1: Pairwise comparison of S. carlsbergensis genome with sub-genome of S. cerevisiae (left) and S. eubayanus (non-cerevisiae) sub-genome (right). Taken from Walther et al, 2014

Summarized, S. carlsbergensis (group I) lost some S. cerevisiae DNA which is still present in the Weihenstephan lager yeast (group II).

Chromosomal map of S. carlsbergensis

The authors generated a chromosomal map for S. carlsbergensis strain CBS 1513 which consists of 29 different chromosomes (Fig 2). Whereas the Weihenstephan lager yeasts harbours 36 different chromosomes (not shown). The individual chromosomes either contain only chromosomal information from the parental S. cerevisiae (parts in blue) or S. eubayanus (orange parts) yeasts or contain information from both yeasts (translocated chromosomes).

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Fig 2: Chromosomal map of S. carlsbergensis strain CBS 1513. Blue parts represent S. cerevisiae sub-genome, orange parts the S. eubayanus sub-genome. Taken from Walther et al, 2014

To investigate if group I lager yeasts resulted from a hybridization event of two haploid (one copy of each chromosome) S. cerevisiae and S. eubayanus cells, the authors determined the copy numbers of each chromosome present in the S. carlsbergensis genome. If this would be the case, one would expect to find a 1:1 ratio of S. cerevisiae and S. eubayanus chromosomes in the S. carlsbergensis genome.

Surprisingly, the S. carlsbergensis genome seems to be triploid (three copies) with one copy of S. cerevisiae and two copies of S. eubayanus genome (1:2 ratio). The complete S. carlsbergensis genome therefore consists of a total of 47 chromosomes (Fig 2). In comparison, the Weihenstephan lager yeasts is tetraploid (4 copies) with two S. cerevisiae and two S. eubayanus genomes (1:1 ratio).

The comparison showed a clear distinction between lager yeast group I and II with loss of S. cerevisiae DNA in group I. In terms of origin, one may suggest that group I lager yeasts were generated by a fusion event of a haploid S. cerevisiae with a diploid S. eubayanus yeast cell whereas group II lager yeasts originated from a diploid-diploid fusion generating tetraploid group II lager yeasts. Three conserved translocation events in both sequenced lager yeasts may however suggest a common ancestor of both lager yeast groups. And a DNA elimination event may have created group I lager yeasts afterwards.

There you have it. A pretty cool research project. I would like to finish with yet another astonishing result. The authors addressed the level of diversity of possibly one of the original S. carlsbergensis yeast strain isolated by Emil Chr. Hansen in the late 19th century (obtained from Carlsberg bottles of the late 19th century) with the strain deposited at CBS in 1947. The yeasts present in the bottles were identical with the CBS deposited yeast strain. “This suggests very limited evolution of pure cultured yeast strains under industrial fermentation conditions” [cited from Walther et al, 2014]. Pretty cool, right?

I hope you enjoyed reading my short review. Please have a look at the original genome paper as well. I think it is very well written publication. Hope to see some new lager yeast genomes coming out soon.

Bibliography

Nakao Y, Kanamori T, Itoh T, Kodama Y, Rainieri S et al (2009) Genome sequence of the lager brewing yeast, an interspecies hybrid. DNA Res. 16:115-129

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BBA/EBY Brett Experiment Update 5

Eureka, we are back to Brett experiment updates. I would like to take the opportunity here to remind people to fill in evaluation data they have so far. At this point, only 6 people (out of 38 collaborators) sent in data either via the provided google doc form or by posting their results on blogs. If you haven’t sent in any data so far, may I kindly ask you to do so? Sending me your evaluation sheets as PDF works as well.

That’s it already. More yeast posts to come soon.