After eluding scholars for decades, a copy of On the Origin of Species with handwritten revisions by Charles Darwin has come to light and is due to be auctioned next month.

Christie’s has put an estimate of £300,000 to £500,000 on the annotated book, which it said will allow “for the first time a precise reading of Darwin’s exact revisions without the veil of reconstruction and translation … [it] provides an insight into his working method, and documents the further development of his ideas for his ‘big book’.”

Darwin’s changes were made on a complete set of loose sheets from the third edition of his masterpiece, which he sent to his German translator for inclusion in the second German edition of On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life. The alterations were then incorporated into the fourth English edition and all subsequent versions of the book, meaning they remain the definitive text of the seminal scientific work.

According to the auction house, the annotated sheets are thought to have been in the possession of the translator, HG Bronn, when he died in 1862. They were subsequently bound, and entered the possession of Darwin’s correspondent, the German palaeontologist Melchior Neumayr. The volume has been in the hands of Neumayr’s descendants until now.

Scholars have known from Darwin’s correspondence that the annotations existed. In March 1862 he wrote, “I should like to make a few more corrections on clean sheets of the last English Edition”, adding in the next month: “I have compared the sheets of the Third English Edition with the Second which was translated into German, & have marked with a pencil line all the additions & corrections … Where merely a few words have been altered I have underlined them with pencil: where a sentence has to be omitted I have marked ‘dele’.”

Some of Charles Darwin’s annotations to On the Origin of Species. Photograph: Christie's

But Christie’s, which is including a letter from Darwin to Neumayr in the lot, said that “their whereabouts and even survival has remained a mystery”.

Christie’s specialist Meg Ford said the revisions made to the text “reflect[ed] Darwin’s ongoing refinement of his scientific research and thinking”. One, in chapter 13, on classification, “encapsulates a discovery Darwin made while working on his book on Orchids in 1861-62, that is, exactly at the time Darwin was marking up these printed sheets to send to Bronn”.

The third edition reads: “As soon as three Orchidean forms (Monachanthus, Myanthus, and Catasetum), which had previously been ranked as three distinct genera, were known to be sometimes produced on the same spike, they were immediately included.” Darwin adds in the margin: “as remarkable variations under the same species; but [I] have recently been enabled to show that they constitute the female, hermaphrodite & male forms of the same orchid.”

Ford said: “His work on orchids relates to his evolutionary theories by showing that orchids evolved to allow cross-fertilisation in a single plant. He is incorporating his own research (as well as that of others elsewhere), in his own hand.”

According to Christie’s, which sold a first edition of On the Origin of Species, with no annotations, for £269,000 last July, while individual pages of autograph drafts from the book “very occasionally” appear on the market, “no other example of Darwin’s autograph revisions to the text are known to have been offered”.

“Annotated copies by him are incredibly rare,” said Ford. “This one really shows him engaging with his text … To have his own thoughts on a text that we know occupied him fully right up until his death is really just remarkable. This physical manifestation of a great scientist grappling with his great work is extraordinary, both in terms of its rarity, and the physical evidence of it.”